Author: Katherine M Hiller, MD, Clinical Assistant Professor, Department of Emergency Medicine, University of ArizonaCoauthor(s): James Li, MD, Former Assistant Professor, Division of Emergency Medicine, Harvard Medical School; Board of Directors, Remote Medicine
Golden Rules of ED Antibiotic Use
Antibiotic therapy ideally is determined by isolation of the offending organism and determination of its antibiotic susceptibility pattern. This information is usually not available in the acute setting of the emergency department (ED), and it is often necessary to make treatment decisions without precise knowledge of infectious source or microbial species. In certain cases (eg, suspected meningitis, gram-negative sepsis, bacterial peritonitis, pneumonia), early empiric therapy may be lifesaving.
The choice of an antimicrobial agent should always be based on the most likely involved organism. Guides, such as the Sanford Guide to Antimicrobial Therapy, are useful in suggesting initial therapy and may be supplemented by knowledge of a certain hospital's susceptibility patterns. Frequently, more than one antibiotic regimen is appropriate for the disease process.
The authors recommend that emergency physicians familiarize themselves with a short list of inexpensive and established antibiotics. These should be considered the main arsenal against microbial disease and, except in unusual circumstances, should be used before other treatments.
Antibiotics prescribed but not taken are worth little to a sick patient. Compliance can be optimized by optimizing drug formulation and minimizing frequency of dosing, duration of treatment, unpleasant side effects, and cost.
For these reasons, single-dose courses administered in the ED (eg, benzathine penicillin, cefixime, ciprofloxacin, fluconazole, metronidazole) greatly improve compliance over traditional multiday multidose regimens.1,2
Throughout this article, antibiotics appearing in boldface are favored by the authors because of their availability, cost, dosing schedule, and spectrum of coverage.
Finally, where possible, pricing for medications has been included as an educational resource for both healthcare workers and patients. Injectable drug prices are current as of 2009 and are taken from the national "Average Wholesale Price" database used by the Centers for Medicare & Medicaid Services. International price comparisons are taken from the International drug price guide. Oral drug prices are taken from national prescription vendors, and include, where applicable, the $4/course formularies adopted in 2008 by WalMart, Hannaford Grocers, KMart, and Rite Aid Pharmacies.Note: A one-page reference table with key therapy recommendations taken from this article can be downloaded in Adobe Acrobat format by clicking the Antibiotics Guidelines Summary.
Recent Updates From the Medical Literature
A late influenza season in 2008-09 and the first influenza pandemic in 40 years in 2009-10 prompted a closer look at the use of antivirals for influenza. In general, antivirals for influenza are only effective if begun within 24-48 hours of onset of symptoms and even then confer at most 3-5 days fewer symptoms. Most healthy persons with illness consistent with influenza do not need antiviral medication. The CDC recommends treating all patients hospitalized for influenza, all patients with lower tract infection or clinical deterioration, all patients younger than 2 years old or older than 65 years old, pregnant and postpartum women, and patients with chronic medical or immunosuppressive conditions.3 An IV neuraminidase inhibitor, peramivir, is now available for inpatient influenza treatment. Current recommendations are detailed later in this article.In 2007, the CDC updated treatment guidelines for gonococcal infection and associated conditions. Fluoroquinolones are no longer recommended to treat gonorrhea in the United States. The recommendation was based on analysis of new data from the CDC’s Gonococcal Isolate Surveillance Project (GISP). The data from GISP showed the proportion of gonorrhea cases in heterosexual men that were fluoroquinolone-resistant (QRNG) reached 6.7%, an 11-fold increase from 0.6% in 2001. This limits treatment of gonorrhea to drugs in the cephalosporin class (ceftriaxone 125 mg IM once as a single dose). Fluoroquinolones may be an alternative treatment option for disseminated gonococcal infection if antimicrobial susceptibility can be documented. For more information, see CDC Updated Gonococcal treatment recommendations.In 2006, the CDC also updated guidelines for tetanus immunization. Adults should receive Tdap instead of Td when receiving boosters during treatment of wounds. Click to jump to details.Penicillin allergy cross-reactivity with cephalosporins is significantly overstated. Cross-reactivity between penicillins and cephalosporins is much less than the 10-15% commonly cited. No cross reactivity exists between penicillins and third-generation cephalosporins. However, if a patient has known anaphylaxis to penicillin, caution with cephalosporin use still is warranted.4,5,6,7
Classically, quinolone antibiotics have been contraindicated in pediatric and pregnant populations due to the joint and cartilage destruction observed in multiple different animal models. Recent reviews of compassionate quinolone use both in the United States and abroad have proposed that this complication is probably not as common in the pediatric population. Approximately 1.5% of patients with cystic fibrosis given ciprofloxacin experienced self-limited arthralgias (also a complication of their disease process). None had joint or cartilage destruction.8 Currently, anthrax is the only FDA-approved indication for quinolones in the pediatric population.
Neisseria meningitidis has become a leading cause of bacterial meningitis in the United States after dramatic reductions in the incidence of Streptococcus pneumoniae that have been achieved using conjugate vaccines.9 A new tetravalent meningococcal vaccine may further alter the pattern of disease and change treatment recommendations during epidemics.
Resistant organisms continue to increase the need for innovative and effective treatments during severe infections. Some of the newer antibiotics on the horizon that may improve our treatment of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) include linezolid, quinupristin, dalfopristin, and daptomycin.10 Additionally, older antibiotics, such as sulfamethoxazole/trimethoprim and doxycycline, may play a role in treatment of MRSA.11 Treatment of simple cellulitis with intravenous (IV) antibiotics administered on a daily basis through the ED or through home health visits is as effective as inpatient treatment.12
Finally, the time of mandated blood cultures prior to administration of antibiotics may be ending. An increasing body of evidence demonstrates lack of clinical usefulness for such infections as pyelonephritis13 , cellulitis14 , and pneumonia15 . However, in the setting of undifferentiated bacteremia, blood should be cultured prior to starting treatment, unless this would cause undue delay. Increasing incidence of community-acquired MRSA may have impact on the value of cultures for certain infections.
Golden Rules of ED Antibiotic Use
Antibiotic therapy ideally is determined by isolation of the offending organism and determination of its antibiotic susceptibility pattern. This information is usually not available in the acute setting of the emergency department (ED), and it is often necessary to make treatment decisions without precise knowledge of infectious source or microbial species. In certain cases (eg, suspected meningitis, gram-negative sepsis, bacterial peritonitis, pneumonia), early empiric therapy may be lifesaving.
The choice of an antimicrobial agent should always be based on the most likely involved organism. Guides, such as the Sanford Guide to Antimicrobial Therapy, are useful in suggesting initial therapy and may be supplemented by knowledge of a certain hospital's susceptibility patterns. Frequently, more than one antibiotic regimen is appropriate for the disease process.
The authors recommend that emergency physicians familiarize themselves with a short list of inexpensive and established antibiotics. These should be considered the main arsenal against microbial disease and, except in unusual circumstances, should be used before other treatments.
Antibiotics prescribed but not taken are worth little to a sick patient. Compliance can be optimized by optimizing drug formulation and minimizing frequency of dosing, duration of treatment, unpleasant side effects, and cost.
For these reasons, single-dose courses administered in the ED (eg, benzathine penicillin, cefixime, ciprofloxacin, fluconazole, metronidazole) greatly improve compliance over traditional multiday multidose regimens.1,2
Throughout this article, antibiotics appearing in boldface are favored by the authors because of their availability, cost, dosing schedule, and spectrum of coverage.
Finally, where possible, pricing for medications has been included as an educational resource for both healthcare workers and patients. Injectable drug prices are current as of 2009 and are taken from the national "Average Wholesale Price" database used by the Centers for Medicare & Medicaid Services. International price comparisons are taken from the International drug price guide. Oral drug prices are taken from national prescription vendors, and include, where applicable, the $4/course formularies adopted in 2008 by WalMart, Hannaford Grocers, KMart, and Rite Aid Pharmacies.Note: A one-page reference table with key therapy recommendations taken from this article can be downloaded in Adobe Acrobat format by clicking the Antibiotics Guidelines Summary.
Recent Updates From the Medical Literature
A late influenza season in 2008-09 and the first influenza pandemic in 40 years in 2009-10 prompted a closer look at the use of antivirals for influenza. In general, antivirals for influenza are only effective if begun within 24-48 hours of onset of symptoms and even then confer at most 3-5 days fewer symptoms. Most healthy persons with illness consistent with influenza do not need antiviral medication. The CDC recommends treating all patients hospitalized for influenza, all patients with lower tract infection or clinical deterioration, all patients younger than 2 years old or older than 65 years old, pregnant and postpartum women, and patients with chronic medical or immunosuppressive conditions.3 An IV neuraminidase inhibitor, peramivir, is now available for inpatient influenza treatment. Current recommendations are detailed later in this article.In 2007, the CDC updated treatment guidelines for gonococcal infection and associated conditions. Fluoroquinolones are no longer recommended to treat gonorrhea in the United States. The recommendation was based on analysis of new data from the CDC’s Gonococcal Isolate Surveillance Project (GISP). The data from GISP showed the proportion of gonorrhea cases in heterosexual men that were fluoroquinolone-resistant (QRNG) reached 6.7%, an 11-fold increase from 0.6% in 2001. This limits treatment of gonorrhea to drugs in the cephalosporin class (ceftriaxone 125 mg IM once as a single dose). Fluoroquinolones may be an alternative treatment option for disseminated gonococcal infection if antimicrobial susceptibility can be documented. For more information, see CDC Updated Gonococcal treatment recommendations.In 2006, the CDC also updated guidelines for tetanus immunization. Adults should receive Tdap instead of Td when receiving boosters during treatment of wounds. Click to jump to details.Penicillin allergy cross-reactivity with cephalosporins is significantly overstated. Cross-reactivity between penicillins and cephalosporins is much less than the 10-15% commonly cited. No cross reactivity exists between penicillins and third-generation cephalosporins. However, if a patient has known anaphylaxis to penicillin, caution with cephalosporin use still is warranted.4,5,6,7
Classically, quinolone antibiotics have been contraindicated in pediatric and pregnant populations due to the joint and cartilage destruction observed in multiple different animal models. Recent reviews of compassionate quinolone use both in the United States and abroad have proposed that this complication is probably not as common in the pediatric population. Approximately 1.5% of patients with cystic fibrosis given ciprofloxacin experienced self-limited arthralgias (also a complication of their disease process). None had joint or cartilage destruction.8 Currently, anthrax is the only FDA-approved indication for quinolones in the pediatric population.
Neisseria meningitidis has become a leading cause of bacterial meningitis in the United States after dramatic reductions in the incidence of Streptococcus pneumoniae that have been achieved using conjugate vaccines.9 A new tetravalent meningococcal vaccine may further alter the pattern of disease and change treatment recommendations during epidemics.
Resistant organisms continue to increase the need for innovative and effective treatments during severe infections. Some of the newer antibiotics on the horizon that may improve our treatment of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) include linezolid, quinupristin, dalfopristin, and daptomycin.10 Additionally, older antibiotics, such as sulfamethoxazole/trimethoprim and doxycycline, may play a role in treatment of MRSA.11 Treatment of simple cellulitis with intravenous (IV) antibiotics administered on a daily basis through the ED or through home health visits is as effective as inpatient treatment.12
Finally, the time of mandated blood cultures prior to administration of antibiotics may be ending. An increasing body of evidence demonstrates lack of clinical usefulness for such infections as pyelonephritis13 , cellulitis14 , and pneumonia15 . However, in the setting of undifferentiated bacteremia, blood should be cultured prior to starting treatment, unless this would cause undue delay. Increasing incidence of community-acquired MRSA may have impact on the value of cultures for certain infections.
Empiric Antibiotic Therapy
Broad-spectrum antibiotics
These agents are generally chosen for empiric treatment of potentially life-threatening infections of unknown bacterial origin. Single agents mostly are related to penicillin (eg, second- or third-generation cephalosporins, imipenem, beta-lactam/beta-lactamase inhibitors [BL/BLI]), with the exception of the newer generation fluoroquinolones and chloramphenicol. This last agent is used widely outside the United States because of its low cost and availability as an inexpensive oral treatment (<$0.01/250 mg tablet).
In the United States, chloramphenicol may be considered an alternative for cases of penicillin-resistant bacteria or for penicillin-allergic patients with sepsis or meningitis. Within the United States, large differences in cost exist between commonly used broad-spectrum antibiotics, as demonstrated by these prices: ceftriaxone ($11/2 g, $15/250 mg), cefotaxime ($23/2 g), imipenem ($82/1 g), ticarcillin/clavulanate ($17/3.1 g), piperacillin/tazobactam ($2/3.375 g), and ampicillin/sulbactam ($13/3 g).
Several new-generation fluoroquinolones have been introduced as powerful broad-spectrum antibiotics. Moxifloxacin and gatifloxacin are marketed and FDA approved for a wide variety of inpatient and ambulatory indications including chronic bronchitis, nosocomial and community-acquired pneumonia, diabetic foot infection, osteomyelitis, and uncomplicated urinary tract infection. These new agents distinguish themselves from older fluoroquinolones by their activity against gram-positive bacteria (eg, penicillin-resistant Streptococcus pneumoniae and Staphylococcus aureus); gram-negative bacteria, and anaerobes. Under most conditions, they achieve equal serum levels whether dosed orally or IV and are given in single daily doses.
Broad-spectrum agents should not be used empirically and indiscriminately for all infections. The major argument against such use is the development of resistant organisms. Routine use of broad-spectrum antibiotics for minor infections significantly adds to infection and colonization of the general population with increasingly hardy microbes that are difficult to treat. According to the Centers for Disease Control and Prevention (CDC) sources, indiscriminate use of broad-spectrum antibiotics more than doubles an individual's chance of acquiring future infection with a resistant organism. The relative risk increases from 3.1 to 5.6.16 For fluoroquinolones, this argument is even more important because resistance is mediated by a single plasmid, which confers resistance to the entire class of agents. Major resistance thus may rapidly be acquired, unless strict controls against widespread use are put into place.
For these reasons, the newer broad-spectrum fluoroquinolones should be reserved as second-line agents for use when traditional broad-spectrum antibiotics are contraindicated or have failed. This approach is similar to some hospital policies reserving use of antimicrobials such as vancomycin, ceftriaxone, and imipenem for special situations.17,18 From a patient-based perspective, such a policy will protect individuals from the more-than-doubled risk of future superinfection with a highly resistant organism. From a population-based perspective, this also will protect communities from multidrug-resistant endemics. Multidrug-resistant S aureus, Enterococcus species, Pseudomonas aeruginosa, malaria, and tuberculosis are current examples of endemics resulting from indiscriminate utilization of antimicrobial therapy.
These agents are generally chosen for empiric treatment of potentially life-threatening infections of unknown bacterial origin. Single agents mostly are related to penicillin (eg, second- or third-generation cephalosporins, imipenem, beta-lactam/beta-lactamase inhibitors [BL/BLI]), with the exception of the newer generation fluoroquinolones and chloramphenicol. This last agent is used widely outside the United States because of its low cost and availability as an inexpensive oral treatment (<$0.01/250 mg tablet).
In the United States, chloramphenicol may be considered an alternative for cases of penicillin-resistant bacteria or for penicillin-allergic patients with sepsis or meningitis. Within the United States, large differences in cost exist between commonly used broad-spectrum antibiotics, as demonstrated by these prices: ceftriaxone ($11/2 g, $15/250 mg), cefotaxime ($23/2 g), imipenem ($82/1 g), ticarcillin/clavulanate ($17/3.1 g), piperacillin/tazobactam ($2/3.375 g), and ampicillin/sulbactam ($13/3 g).
Several new-generation fluoroquinolones have been introduced as powerful broad-spectrum antibiotics. Moxifloxacin and gatifloxacin are marketed and FDA approved for a wide variety of inpatient and ambulatory indications including chronic bronchitis, nosocomial and community-acquired pneumonia, diabetic foot infection, osteomyelitis, and uncomplicated urinary tract infection. These new agents distinguish themselves from older fluoroquinolones by their activity against gram-positive bacteria (eg, penicillin-resistant Streptococcus pneumoniae and Staphylococcus aureus); gram-negative bacteria, and anaerobes. Under most conditions, they achieve equal serum levels whether dosed orally or IV and are given in single daily doses.
Broad-spectrum agents should not be used empirically and indiscriminately for all infections. The major argument against such use is the development of resistant organisms. Routine use of broad-spectrum antibiotics for minor infections significantly adds to infection and colonization of the general population with increasingly hardy microbes that are difficult to treat. According to the Centers for Disease Control and Prevention (CDC) sources, indiscriminate use of broad-spectrum antibiotics more than doubles an individual's chance of acquiring future infection with a resistant organism. The relative risk increases from 3.1 to 5.6.16 For fluoroquinolones, this argument is even more important because resistance is mediated by a single plasmid, which confers resistance to the entire class of agents. Major resistance thus may rapidly be acquired, unless strict controls against widespread use are put into place.
For these reasons, the newer broad-spectrum fluoroquinolones should be reserved as second-line agents for use when traditional broad-spectrum antibiotics are contraindicated or have failed. This approach is similar to some hospital policies reserving use of antimicrobials such as vancomycin, ceftriaxone, and imipenem for special situations.17,18 From a patient-based perspective, such a policy will protect individuals from the more-than-doubled risk of future superinfection with a highly resistant organism. From a population-based perspective, this also will protect communities from multidrug-resistant endemics. Multidrug-resistant S aureus, Enterococcus species, Pseudomonas aeruginosa, malaria, and tuberculosis are current examples of endemics resulting from indiscriminate utilization of antimicrobial therapy.
Cephalosporins
When in doubt, second- or third-generation cephalosporins are a good choice for many bacterial infections. Antimicrobial coverage is largely similar within this class and includes gram-positive, gram-negative, and strict anaerobic species. Coverage differences are minor and are primarily relevant if P aeruginosa is suspected (see Pseudomonal infection section). Examples of this class include cefmetazole, cefuroxime, cefoxitin, cefotetan, and cefamandole.
In certain hospitals, one second- or third-generation cephalosporin may be less expensive than others due to special agreements with the supplier. Use the least expensive one if there is significant cost savings. However, relative to the cost of IV setup (>$100), cost differences between cephalosporins may be small. Published average market prices to pharmacies for typical unit doses of these drugs are as follows: cefuroxime ($13/1.5 g), cefepime ($45/2 g), cefoxitin ($23/2 g), cefotaxime ($23/2 g), ceftazidime ($36/2 g), and ceftriaxone ($11/2 g).
When in doubt, second- or third-generation cephalosporins are a good choice for many bacterial infections. Antimicrobial coverage is largely similar within this class and includes gram-positive, gram-negative, and strict anaerobic species. Coverage differences are minor and are primarily relevant if P aeruginosa is suspected (see Pseudomonal infection section). Examples of this class include cefmetazole, cefuroxime, cefoxitin, cefotetan, and cefamandole.
In certain hospitals, one second- or third-generation cephalosporin may be less expensive than others due to special agreements with the supplier. Use the least expensive one if there is significant cost savings. However, relative to the cost of IV setup (>$100), cost differences between cephalosporins may be small. Published average market prices to pharmacies for typical unit doses of these drugs are as follows: cefuroxime ($13/1.5 g), cefepime ($45/2 g), cefoxitin ($23/2 g), cefotaxime ($23/2 g), ceftazidime ($36/2 g), and ceftriaxone ($11/2 g).
Anaerobic coverage
Antibiotics with good anaerobic coverage include metronidazole (<$1/500 mg PO, $3/500 mg IV), clindamycin ($4/600 mg IV), and any BL/BLI (amoxicillin/clavulanate [$5/850 mg PO]; ampicillin/sulbactam [$13/3 g], piperacillin/tazobactam [$2/3.375 g]). For surgical and gynecologic cases in which soiled peritoneum is possible, metronidazole must be used because it is the only agent that covers Bacteroides fragilis, the most common colonic microbe. Although practically all antibiotics have been associated with Clostridium difficile colitis, clindamycin bears the dubious distinction of causing the most cases of this potentially fatal adverse effect. For this reason, metronidazole is the preferred agent for anaerobic coverage.
Pseudomonal coverage
If serious pseudomonal infection is suspected, double coverage is recommended. Antibiotics with activity against P aeruginosa include ceftazidime, ticarcillin, aminoglycosides, imipenem, meropenem, levofloxacin, and ciprofloxacin. As for other antimicrobial regimens, the two agents chosen should be from different classes. For example, the combination of ticarcillin/ tobramycin is good, whereas a combination of ceftazidime and imipenem is not. Piperacillin/tazobactam is a poor choice for treating pseudomonal infections unless used in higher-than-normal doses and combined with an aminoglycoside. Deaths have been reported from pseudomonal infections when using manufacturer-recommended doses of this drug, even when combined with a second agent.
Antibiotics with good anaerobic coverage include metronidazole (<$1/500 mg PO, $3/500 mg IV), clindamycin ($4/600 mg IV), and any BL/BLI (amoxicillin/clavulanate [$5/850 mg PO]; ampicillin/sulbactam [$13/3 g], piperacillin/tazobactam [$2/3.375 g]). For surgical and gynecologic cases in which soiled peritoneum is possible, metronidazole must be used because it is the only agent that covers Bacteroides fragilis, the most common colonic microbe. Although practically all antibiotics have been associated with Clostridium difficile colitis, clindamycin bears the dubious distinction of causing the most cases of this potentially fatal adverse effect. For this reason, metronidazole is the preferred agent for anaerobic coverage.
Pseudomonal coverage
If serious pseudomonal infection is suspected, double coverage is recommended. Antibiotics with activity against P aeruginosa include ceftazidime, ticarcillin, aminoglycosides, imipenem, meropenem, levofloxacin, and ciprofloxacin. As for other antimicrobial regimens, the two agents chosen should be from different classes. For example, the combination of ticarcillin/ tobramycin is good, whereas a combination of ceftazidime and imipenem is not. Piperacillin/tazobactam is a poor choice for treating pseudomonal infections unless used in higher-than-normal doses and combined with an aminoglycoside. Deaths have been reported from pseudomonal infections when using manufacturer-recommended doses of this drug, even when combined with a second agent.
Antibiotic-resistant gram-positive cocci
Several species of resistant gram-positive cocci warrant special consideration. Many are sufficiently virulent that an incorrect choice of initial antibiotic may rapidly be fatal to the patient. Recent reports hallmark the increasing incidence of community-acquired MRSA. Such cases actually represent infection by one of two subspecies of S aureus that are genotypically and phenotypically distinct.
The more traditional nosocomially-acquired MRSA has also been identified in the community in increasing numbers. This strain of MRSA is multidrug resistant, making treatment a challenge. True community-acquired MRSA is a different strain of S aureus and (while resistant to methicillin) is susceptible to many common treatment regimens.
Vancomycin ($8/2 g) should be used initially for any suspected severe infection, including line sepsis, endocarditis, and meningitis. In special cases of severe infection, other newer agents may be used instead of vancomycin. These cases include patients who have been hospitalized within the past 24 months, have had outpatient visits within the past 12 months, have been admitted to a nursing home within the past 12 months, have been on antibiotics within the past 12 months, have undergone hemodialysis, have chronic illnesses, are intravenous drug users, or are in close contact with other persons with MRSA. Such patients may receive linezolid ($119/600 mg), or daptomycin ($248/500 mg) instead of vancomycin.If the patient has no risk factors for the nosocomial-type MRSA, antibiotics with historical effectiveness against S aureus may be used. These include nafcillin, trimethoprim/sulfamethoxazole (TMP-SMZ), and clindamycin. However, if any form of nosocomial-type MRSA is possible, treatment with vancomycin or newer agents should be continued until cultures exclude MRSA or, in the presence of MRSA, prove its sensitivity to other agents.
Minor infections with non-nosocomial-type community-acquired MRSA may be treated with a penicillinase-resistant penicillins (oxacillin, dicloxacillin), first-generation cephalosporins, TMP-SMZ, or tetracyclines.10 Coverage should be tailored by reviewing the local antibiogram for MRSA and should include streptococcal coverage when appropriate.
Several species of resistant gram-positive cocci warrant special consideration. Many are sufficiently virulent that an incorrect choice of initial antibiotic may rapidly be fatal to the patient. Recent reports hallmark the increasing incidence of community-acquired MRSA. Such cases actually represent infection by one of two subspecies of S aureus that are genotypically and phenotypically distinct.
The more traditional nosocomially-acquired MRSA has also been identified in the community in increasing numbers. This strain of MRSA is multidrug resistant, making treatment a challenge. True community-acquired MRSA is a different strain of S aureus and (while resistant to methicillin) is susceptible to many common treatment regimens.
Vancomycin ($8/2 g) should be used initially for any suspected severe infection, including line sepsis, endocarditis, and meningitis. In special cases of severe infection, other newer agents may be used instead of vancomycin. These cases include patients who have been hospitalized within the past 24 months, have had outpatient visits within the past 12 months, have been admitted to a nursing home within the past 12 months, have been on antibiotics within the past 12 months, have undergone hemodialysis, have chronic illnesses, are intravenous drug users, or are in close contact with other persons with MRSA. Such patients may receive linezolid ($119/600 mg), or daptomycin ($248/500 mg) instead of vancomycin.If the patient has no risk factors for the nosocomial-type MRSA, antibiotics with historical effectiveness against S aureus may be used. These include nafcillin, trimethoprim/sulfamethoxazole (TMP-SMZ), and clindamycin. However, if any form of nosocomial-type MRSA is possible, treatment with vancomycin or newer agents should be continued until cultures exclude MRSA or, in the presence of MRSA, prove its sensitivity to other agents.
Minor infections with non-nosocomial-type community-acquired MRSA may be treated with a penicillinase-resistant penicillins (oxacillin, dicloxacillin), first-generation cephalosporins, TMP-SMZ, or tetracyclines.10 Coverage should be tailored by reviewing the local antibiogram for MRSA and should include streptococcal coverage when appropriate.
HIV-infected patients
Community-acquired bacterial pneumonia is the most common cause of pneumonia among all HIV-infected individuals. However, other pathogens must be considered because of the relative immunocompromise in these patients, particularly in those with diminished CD4+ cell counts. Pulmonary tuberculosis (TB), coccidioidomycosis, and other diseases present atypically in HIV-infected patients. In HIV-infected patients with cough, the presence of prior TB exposure, hemoptysis, nocturnal sweats, weight loss, or a previously positive purified protein derivative (PPD) skin test result should prompt rapid patient isolation in a negative-pressure room and initiation of a TB workup (ie, TB-specific blood cultures, sputum staining, and culture). For further information, see Tuberculosis.If suspicion is high, isolating such patients even without overt symptoms is sometimes appropriate. Chest radiographic findings can be normal in 20% of cases of HIV-associated pulmonary TB.
In patients with CD4+ counts less than 200/mm3 who are not receiving prophylaxis, IV TMP-SMZ should be used to cover Pneumocystis carinii pneumonia (PCP). Additionally, a 1990 report by the National Institutes of Health/University of California concluded that prednisone 40 mg by mouth twice daily has been shown to reduce mortality in patients with PCP when the PO2 is <70>35. Note that the mortality rate is high even with therapy: 10-20% in patients without hypoxia and 20-40% in patients with hypoxia.19
Gram-negative sepsis
Gram-negative sepsis is associated with high rates of morbidity and mortality due to production of bacterial endotoxin. For presumptive treatment of life-threatening sepsis in adults, coverage for possible gram-negative bacteremia is recommended using two antibiotics with good gram-negative activity.20 Good choices include a third-generation cephalosporin or BL/BLI, plus a fluoroquinolone or an aminoglycoside. Examples of such coverage include ceftriaxone and gentamicin, or cefmetazole and ciprofloxacin. Many possible drug combinations are acceptable as long as the antibiotics are not of the same class.
Community-acquired bacterial pneumonia is the most common cause of pneumonia among all HIV-infected individuals. However, other pathogens must be considered because of the relative immunocompromise in these patients, particularly in those with diminished CD4+ cell counts. Pulmonary tuberculosis (TB), coccidioidomycosis, and other diseases present atypically in HIV-infected patients. In HIV-infected patients with cough, the presence of prior TB exposure, hemoptysis, nocturnal sweats, weight loss, or a previously positive purified protein derivative (PPD) skin test result should prompt rapid patient isolation in a negative-pressure room and initiation of a TB workup (ie, TB-specific blood cultures, sputum staining, and culture). For further information, see Tuberculosis.If suspicion is high, isolating such patients even without overt symptoms is sometimes appropriate. Chest radiographic findings can be normal in 20% of cases of HIV-associated pulmonary TB.
In patients with CD4+ counts less than 200/mm3 who are not receiving prophylaxis, IV TMP-SMZ should be used to cover Pneumocystis carinii pneumonia (PCP). Additionally, a 1990 report by the National Institutes of Health/University of California concluded that prednisone 40 mg by mouth twice daily has been shown to reduce mortality in patients with PCP when the PO2 is <70>35. Note that the mortality rate is high even with therapy: 10-20% in patients without hypoxia and 20-40% in patients with hypoxia.19
Gram-negative sepsis
Gram-negative sepsis is associated with high rates of morbidity and mortality due to production of bacterial endotoxin. For presumptive treatment of life-threatening sepsis in adults, coverage for possible gram-negative bacteremia is recommended using two antibiotics with good gram-negative activity.20 Good choices include a third-generation cephalosporin or BL/BLI, plus a fluoroquinolone or an aminoglycoside. Examples of such coverage include ceftriaxone and gentamicin, or cefmetazole and ciprofloxacin. Many possible drug combinations are acceptable as long as the antibiotics are not of the same class.
Bacterial meningitis
In the setting of suspected meningitis, antibiotics should be initiated immediately, preferably before or at the same time cerebrospinal fluid (CSF) is drawn for analysis.21 Antibiotics will not affect CSF cell counts for several hours, and more importantly, the patient will receive early treatment for a possibly rapidly progressive disease. For immune-competent adults, use a third-generation cephalosporin alone (ceftriaxone, $11/2g). For infants, elderly, or immunocompromised patients (eg, alcoholics, patients with renal failure), add ampicillin to cover Listeria monocytogenes. In regions with documented highly resistant pneumococcus, the CDC recommends adding vancomycin until culture results are available. In suspected herpes simplex encephalitis, especially in neonates, addition of acyclovir should be included empirically.22
In the setting of suspected meningitis, antibiotics should be initiated immediately, preferably before or at the same time cerebrospinal fluid (CSF) is drawn for analysis.21 Antibiotics will not affect CSF cell counts for several hours, and more importantly, the patient will receive early treatment for a possibly rapidly progressive disease. For immune-competent adults, use a third-generation cephalosporin alone (ceftriaxone, $11/2g). For infants, elderly, or immunocompromised patients (eg, alcoholics, patients with renal failure), add ampicillin to cover Listeria monocytogenes. In regions with documented highly resistant pneumococcus, the CDC recommends adding vancomycin until culture results are available. In suspected herpes simplex encephalitis, especially in neonates, addition of acyclovir should be included empirically.22
Pneumonia
The American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) have both published guidelines for the treatment of community-acquired pneumonia (CAP).23,24 For outpatient treatment of pneumonia, both recommend either a macrolide (clarithromycin or azithromycin) or doxycycline. For outpatient treatment, the IDSA guidelines also suggest single-agent treatment with a respiratory fluoroquinolone. However, the ATS guidelines reserve single- and double-agent fluoroquinolone treatment (the latter with an added beta-lactam drug) for outpatient treatment of patients with pulmonary or cardiac comorbidities. The beta-lactam agent is suggested due to the greater prevalence and morbidity of gram-negative infection in this population. Ciprofloxacin is generally a poor choice for CAP due to its poor coverage of Streptococcus pneumoniae.25,26
Inpatient treatment regimens for pneumonia include monotherapy with a respiratory fluoroquinolone or combination therapy with both IV beta-lactam and macrolide agents together. For patients with no comorbidity and no risk factors for gram-negative organisms or drug-resistant Pneumococcus, ATS endorses monotherapy with IV azithromycin alone. The IDSA recommends that all treatment regimens for ICU-admitted patients include a beta-lactam. Patients with acute necrotizing pneumonia should receive vancomycin to cover MRSA. Both organizations' recommendations cover the 7 most likely pathogens causing pneumonia: S pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, S aureus, Mycoplasma pneumoniae, Legionella pneumoniae, and Chlamydia pneumoniae.
Institutionalized patients and patients with structural lung disease are at risk for pseudomonal pneumonia. For these and other patients at risk for such infection, at least two antipseudomonal antibiotics with activity against drug-resistant Pneumococcus and Legionella are warranted (eg, BL/BLI plus ciprofloxacin).
The American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) have both published guidelines for the treatment of community-acquired pneumonia (CAP).23,24 For outpatient treatment of pneumonia, both recommend either a macrolide (clarithromycin or azithromycin) or doxycycline. For outpatient treatment, the IDSA guidelines also suggest single-agent treatment with a respiratory fluoroquinolone. However, the ATS guidelines reserve single- and double-agent fluoroquinolone treatment (the latter with an added beta-lactam drug) for outpatient treatment of patients with pulmonary or cardiac comorbidities. The beta-lactam agent is suggested due to the greater prevalence and morbidity of gram-negative infection in this population. Ciprofloxacin is generally a poor choice for CAP due to its poor coverage of Streptococcus pneumoniae.25,26
Inpatient treatment regimens for pneumonia include monotherapy with a respiratory fluoroquinolone or combination therapy with both IV beta-lactam and macrolide agents together. For patients with no comorbidity and no risk factors for gram-negative organisms or drug-resistant Pneumococcus, ATS endorses monotherapy with IV azithromycin alone. The IDSA recommends that all treatment regimens for ICU-admitted patients include a beta-lactam. Patients with acute necrotizing pneumonia should receive vancomycin to cover MRSA. Both organizations' recommendations cover the 7 most likely pathogens causing pneumonia: S pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, S aureus, Mycoplasma pneumoniae, Legionella pneumoniae, and Chlamydia pneumoniae.
Institutionalized patients and patients with structural lung disease are at risk for pseudomonal pneumonia. For these and other patients at risk for such infection, at least two antipseudomonal antibiotics with activity against drug-resistant Pneumococcus and Legionella are warranted (eg, BL/BLI plus ciprofloxacin).
Other Respiratory Infections
Bronchitis
Unless the patient has COPD or another compelling reason, do not prescribe antibiotics for acute bronchitis.27,28 Acute bronchitis appears clinically similar to pneumonia (eg, fever, productive cough). However, examination and radiographic findings of pneumonia are lacking. Most of these cases are viral.29 Over-prescription of antibiotics in this population is a major source of resistance. It also doubles an individual patient's chance of later contracting a resistant infection.30 Consider making exceptions for patients with severe underlying disease (eg, congestive heart failure) who would be unable to tolerate the small risk of bacterial infection or for patients who are symptomatic for more than 10 days, in whom Mycoplasma infection becomes a greater possibility.
In contrast to the general guideline of withholding antibiotics for acute bronchitis, antibiotics are indicated for patients with COPD with an acute exacerbation of chronic bronchitis.31 Chronic bronchitis is defined as a productive cough for 3 or more months per year for 2 or more years. Acute exacerbation of chronic bronchitis is defined as an increase in cough, sputum production, dyspnea, or wheezing. Fever is not usually present, and examination or radiographic findings of pneumonia are lacking. Recommendations include TMP-SMZ ($4/10-d course), azithromycin ($26/course), or doxycycline ($4/10-d course).
Except in streptococcal pharyngitis, doxycycline ($4/10-d course) or TMP-SMZ ($4/10-d course) are as effective for respiratory tract infections as any extended-spectrum oral cephalosporin (eg, cefuroxime, cefadroxil, cefpodoxime, and cefaclor), which are all prohibitively expensive ($97, $140, $114, and $114/10-d course, respectively). However, a generic version of cefaclor is available in some areas ($42/10-d course). Consequently, for pricing reasons, doxycycline or TMP-SMZ are recommended in any situation in which such cephalosporins are considered.32
Unless the patient has COPD or another compelling reason, do not prescribe antibiotics for acute bronchitis.27,28 Acute bronchitis appears clinically similar to pneumonia (eg, fever, productive cough). However, examination and radiographic findings of pneumonia are lacking. Most of these cases are viral.29 Over-prescription of antibiotics in this population is a major source of resistance. It also doubles an individual patient's chance of later contracting a resistant infection.30 Consider making exceptions for patients with severe underlying disease (eg, congestive heart failure) who would be unable to tolerate the small risk of bacterial infection or for patients who are symptomatic for more than 10 days, in whom Mycoplasma infection becomes a greater possibility.
In contrast to the general guideline of withholding antibiotics for acute bronchitis, antibiotics are indicated for patients with COPD with an acute exacerbation of chronic bronchitis.31 Chronic bronchitis is defined as a productive cough for 3 or more months per year for 2 or more years. Acute exacerbation of chronic bronchitis is defined as an increase in cough, sputum production, dyspnea, or wheezing. Fever is not usually present, and examination or radiographic findings of pneumonia are lacking. Recommendations include TMP-SMZ ($4/10-d course), azithromycin ($26/course), or doxycycline ($4/10-d course).
Except in streptococcal pharyngitis, doxycycline ($4/10-d course) or TMP-SMZ ($4/10-d course) are as effective for respiratory tract infections as any extended-spectrum oral cephalosporin (eg, cefuroxime, cefadroxil, cefpodoxime, and cefaclor), which are all prohibitively expensive ($97, $140, $114, and $114/10-d course, respectively). However, a generic version of cefaclor is available in some areas ($42/10-d course). Consequently, for pricing reasons, doxycycline or TMP-SMZ are recommended in any situation in which such cephalosporins are considered.32
Influenza
The majority of influenza cases are due to influenza A. Amantadine and rimantadine have been approved for many years for use against influenza A. However, since 2005, neither are recommended by the CDC because significant resistance has evolved for both drugs. Neuraminidase inhibitors, such as oseltamivir and zanamivir, have variable resistance patterns to seasonal influenza, and each are associated with significant gastrointestinal (oseltamivir) and respiratory (zanamivir) side effects.For the 2009-10 influenza season, the CDC recommends treating all patients hospitalized for influenza, all patients with lower tract infection or clinical deterioration, all patients younger than 2 years or older than 65 years, pregnant and postpartum women, and patients with chronic medical or immunosuppressive conditions.3 An IV neuraminidase inhibitor, peramivir, is now available for inpatient influenza treatment.Antivirals for influenza are only effective if begun within 24-48 hours of onset of symptoms, and even then confer at most 3-5 days of fewer symptoms. Most healthy persons with illness consistent with influenza do not need antiviral medication.Prophylaxis for influenza with antiviral medication may decrease disease and may be considered when the patient is at high risk for influenza-related complications and has had close contact with someone likely to have had influenza. However, the CDC recommends education on the signs and symptoms of influenza with instructions to initiate early treatment as a preferred strategy for control.
The majority of influenza cases are due to influenza A. Amantadine and rimantadine have been approved for many years for use against influenza A. However, since 2005, neither are recommended by the CDC because significant resistance has evolved for both drugs. Neuraminidase inhibitors, such as oseltamivir and zanamivir, have variable resistance patterns to seasonal influenza, and each are associated with significant gastrointestinal (oseltamivir) and respiratory (zanamivir) side effects.For the 2009-10 influenza season, the CDC recommends treating all patients hospitalized for influenza, all patients with lower tract infection or clinical deterioration, all patients younger than 2 years or older than 65 years, pregnant and postpartum women, and patients with chronic medical or immunosuppressive conditions.3 An IV neuraminidase inhibitor, peramivir, is now available for inpatient influenza treatment.Antivirals for influenza are only effective if begun within 24-48 hours of onset of symptoms, and even then confer at most 3-5 days of fewer symptoms. Most healthy persons with illness consistent with influenza do not need antiviral medication.Prophylaxis for influenza with antiviral medication may decrease disease and may be considered when the patient is at high risk for influenza-related complications and has had close contact with someone likely to have had influenza. However, the CDC recommends education on the signs and symptoms of influenza with instructions to initiate early treatment as a preferred strategy for control.
Common Outpatient Infections: Above the Belt
In late 1997, the CDC launched a major campaign to educate physicians and patients about the dangers of inappropriately using antibiotics for coughs, colds, and sore throats. New guidelines and patient brochures are being developed so physicians will be able to advise their patients while being supported by federal recommendations (see Images 1-3). Educational materials are available free of charge from the CDC at (404) 639-2215.
Sinusitis
Both physicians and patients over-diagnose acute sinusitis. Distinguishing it from chronic sinusitis, which has a different treatment and prognosis, is important. Acute sinusitis typically presents with nasal congestion, purulent nasal discharge, and facial pain. In the immunocompetent host, antibiotics are initially unnecessary.33 Initial treatment should consist of topical decongestants used every 4 hours, steam inhalations, saline flushes and advice to sleep in a semi-upright position to facilitate drainage if the maxillary sinus is involved. Antibiotics should be used in toxic-appearing patients, those in whom initial therapy fails, and patients with comorbid conditions.34 TMP-SMZ for 3 days is as effective as a traditional 10-day course ($4/course).35
Sinusitis
Both physicians and patients over-diagnose acute sinusitis. Distinguishing it from chronic sinusitis, which has a different treatment and prognosis, is important. Acute sinusitis typically presents with nasal congestion, purulent nasal discharge, and facial pain. In the immunocompetent host, antibiotics are initially unnecessary.33 Initial treatment should consist of topical decongestants used every 4 hours, steam inhalations, saline flushes and advice to sleep in a semi-upright position to facilitate drainage if the maxillary sinus is involved. Antibiotics should be used in toxic-appearing patients, those in whom initial therapy fails, and patients with comorbid conditions.34 TMP-SMZ for 3 days is as effective as a traditional 10-day course ($4/course).35
Otitis media
Ironically, no type I scientific evidence exists for empiric treatment of otitis media, despite the fact that antibiotics are almost universally used in the United States for such infection. Standard of care in Europe is initial observation. However, antibiotic therapy in the United States has huge financial implications, accounting for $4 billion in annual costs and some 25% of all medical prescriptions.36
In a large review (n=5,400), 81% of patients with otitis media had spontaneous clinical resolution.37 Four studies found no difference in cure rate between traditionally prescribed oral antibiotic regimens and single-dose IM ceftriaxone, dosed 50 mg/kg.38,39,40 In the fourth study (RCT, n=648), investigators found that parents uniformly preferred IM dosing to the traditional course of oral antibiotics.41 Consider a single dose of ceftriaxone IM if antibiotics are to be used.
Ironically, no type I scientific evidence exists for empiric treatment of otitis media, despite the fact that antibiotics are almost universally used in the United States for such infection. Standard of care in Europe is initial observation. However, antibiotic therapy in the United States has huge financial implications, accounting for $4 billion in annual costs and some 25% of all medical prescriptions.36
In a large review (n=5,400), 81% of patients with otitis media had spontaneous clinical resolution.37 Four studies found no difference in cure rate between traditionally prescribed oral antibiotic regimens and single-dose IM ceftriaxone, dosed 50 mg/kg.38,39,40 In the fourth study (RCT, n=648), investigators found that parents uniformly preferred IM dosing to the traditional course of oral antibiotics.41 Consider a single dose of ceftriaxone IM if antibiotics are to be used.
Pharyngitis
Acute pharyngitis is most commonly caused by viruses. However, in order to prevent rheumatic fever and its complications, group A beta-hemolytic streptococcal (GABHS) pharyngitis should be recognized and treated. For compliance reasons, single-dose benzathine penicillin ($56/1.2 mU) is recommended for GABHS pharyngitis or tonsillitis. The recommended dosage is 600,000 units intramuscularly for patients weighing 27 kg or less, and 1,200,000 units for patients weighing more than 27 kg. If oral penicillin must be used, twice-daily dosing has been found as effective as 4-time daily dosing ($8/500 mg bid for 10 d). A full 10-day course is necessary for eradication.42,43,44 Suitable alternatives for cases of penicillin allergy are oral erythromycin for 10 days ($10/course) or azithromycin 500 mg PO for one dose then 250 mg PO daily for 4 days ($26/course).
In some hospitals, rapid streptococcal antigen detection kits are available. They are highly specific but lack sensitivity. Therefore, a throat culture should always be sent when 48-hour follow-up is possible. Because throat cultures are often impractical for ED use, various criteria correlating clinical findings with positive cultures have been developed.45 According to one authority, patients should be treated in the emergency department for presumed GABHS when the incidence of GABHS pharyngitis and its complications are high, when patients are contacts of others with documented GABHS, in patients with scarlet fever, and in areas without adequate laboratory facilities to perform a rapid strep test.46 Another authority adds lack of cough to the list of accompanied findings but recommends empiric treatment if 2 or more of these 4 findings are present.47
Several trials have demonstrated shortened clinical courses of pharyngitis when steroids (dexamethasone, betamethasone, and prednisone) were coadministered with antibiotics.48,49,50 Antibiotics should always be administered with steroids in this setting to prevent overwhelming bacteremia. Death in a previously healthy adolescent has been reported from disseminated infection associated with adjunctive steroid treatment for pharyngitis.51 Steroids are not recommended in patients who are pregnant or have HIV, thrush, or ulcerative pharyngitis.
Acute pharyngitis is most commonly caused by viruses. However, in order to prevent rheumatic fever and its complications, group A beta-hemolytic streptococcal (GABHS) pharyngitis should be recognized and treated. For compliance reasons, single-dose benzathine penicillin ($56/1.2 mU) is recommended for GABHS pharyngitis or tonsillitis. The recommended dosage is 600,000 units intramuscularly for patients weighing 27 kg or less, and 1,200,000 units for patients weighing more than 27 kg. If oral penicillin must be used, twice-daily dosing has been found as effective as 4-time daily dosing ($8/500 mg bid for 10 d). A full 10-day course is necessary for eradication.42,43,44 Suitable alternatives for cases of penicillin allergy are oral erythromycin for 10 days ($10/course) or azithromycin 500 mg PO for one dose then 250 mg PO daily for 4 days ($26/course).
In some hospitals, rapid streptococcal antigen detection kits are available. They are highly specific but lack sensitivity. Therefore, a throat culture should always be sent when 48-hour follow-up is possible. Because throat cultures are often impractical for ED use, various criteria correlating clinical findings with positive cultures have been developed.45 According to one authority, patients should be treated in the emergency department for presumed GABHS when the incidence of GABHS pharyngitis and its complications are high, when patients are contacts of others with documented GABHS, in patients with scarlet fever, and in areas without adequate laboratory facilities to perform a rapid strep test.46 Another authority adds lack of cough to the list of accompanied findings but recommends empiric treatment if 2 or more of these 4 findings are present.47
Several trials have demonstrated shortened clinical courses of pharyngitis when steroids (dexamethasone, betamethasone, and prednisone) were coadministered with antibiotics.48,49,50 Antibiotics should always be administered with steroids in this setting to prevent overwhelming bacteremia. Death in a previously healthy adolescent has been reported from disseminated infection associated with adjunctive steroid treatment for pharyngitis.51 Steroids are not recommended in patients who are pregnant or have HIV, thrush, or ulcerative pharyngitis.
Common Outpatient Infections: Below the Belt
Urinary tract infections
A single dose or 3-day course TMP-SMZ is recommended for simple cases of cystitis ($1/single dose, $4/3-d course). In areas where resistance of Escherichia coli to TMP/SMX is greater than 10-20%, ciprofloxacin should be used instead.52 Use a 10-14-day course in patients who are male, preteen, older than 65 years, use a diaphragm, have diabetes, have recent recurrences of UTI, or have symptoms lasting more than a week. Pyelonephritis should be treated for 14 days.
Pelvic/vaginal infections
Treating vaginal candidiasis with a single dose of oral fluconazole (150 mg, $12/dose) is cheaper and more effective than topical preparations. Trichomoniasis and bacterial vaginosis can both be treated with a single oral dose of metronidazole ($3/2 g).
Distinguish pelvic inflammatory disease (PID) from simple cervicitis. Although the causative bacterial species are similar, outpatient PID should not be treated with single-dose oral agents but with IM ceftriaxone ($15/250 mg) plus doxycycline for 14 days ($4/course). If parenteral cephalosporin therapy is not feasible, use of fluoroquinolones (eg, levofloxacin 500 mg PO qd for 14 d [$195/course] or ofloxacin 400 mg PO bid for 14 d [$175/course]) with or without metronidazole (500 mg PO bid for 14 d [$4/course]) may be considered if the community prevalence and individual risk of gonorrhea is low. Increasing fluoroquinolone resistance in gonococcal isolates necessitates treatment regimens that do not rely on fluoroquinolones for gonococcal coverage. Tests for gonorrhea must be performed prior to instituting therapy and if positive, the patient managed without fluoroquinolone therapy.For more information see, Recent Updates From the Medical Literature.
Patients with suspected cervicitis must be treated for both gonococcal and chlamydial infection because co-infection exists in up to 40% of cases. Use cefixime 400 mg orally once plus azithromycin 1 g orally once ($39/1 g). Although the manufacturer of cefixime discontinued the drug in 2002, Lupin Limited began to re-manufacture cefixime in 2004. Supplies are still limited. As an alternative to the above regimen, 2 g of azithromycin in a single dose covers both gonococcal and chlamydial cervicitis; however, an increased incidence of gastrointestinal side effects exists. The single-dose regimens for chlamydia are recommended over the traditional 10-day doxycycline treatment because overall compliance with a 10-day regimen is dismal. In one survey, of 386 women given 10-day prescriptions of doxycycline for PID, only a third reported compliance. Of the rest, 41% stopped their medication after 4 days, and the remainder never filled their prescriptions.
Note that none of these therapies except for an extended course of doxycycline (14-d bid) adequately covers syphilis. Although the incidence of syphilis has diminished greatly in the United States, it has reemerged in recent years. A quarter of these cases occur in HIV-positive patients. In patients diagnosed with a sexually transmitted disease, consider obtaining syphilis serologic tests (eg, rapid plasma reagin [RPR], venereal disease research laboratory [VDRL]). Patients should have adequate follow-up in the event serologic testing demonstrates the disease. In 1998, the CDC changed its recommended treatment of primary syphilis from a single dose to 3 weekly doses of benzathine penicillin ($112/2.4 mU IM). In cases of neurosyphilis, recommended treatment is 2 weeks of inpatient IV penicillin (4 mU IV q4h).
A single dose or 3-day course TMP-SMZ is recommended for simple cases of cystitis ($1/single dose, $4/3-d course). In areas where resistance of Escherichia coli to TMP/SMX is greater than 10-20%, ciprofloxacin should be used instead.52 Use a 10-14-day course in patients who are male, preteen, older than 65 years, use a diaphragm, have diabetes, have recent recurrences of UTI, or have symptoms lasting more than a week. Pyelonephritis should be treated for 14 days.
Pelvic/vaginal infections
Treating vaginal candidiasis with a single dose of oral fluconazole (150 mg, $12/dose) is cheaper and more effective than topical preparations. Trichomoniasis and bacterial vaginosis can both be treated with a single oral dose of metronidazole ($3/2 g).
Distinguish pelvic inflammatory disease (PID) from simple cervicitis. Although the causative bacterial species are similar, outpatient PID should not be treated with single-dose oral agents but with IM ceftriaxone ($15/250 mg) plus doxycycline for 14 days ($4/course). If parenteral cephalosporin therapy is not feasible, use of fluoroquinolones (eg, levofloxacin 500 mg PO qd for 14 d [$195/course] or ofloxacin 400 mg PO bid for 14 d [$175/course]) with or without metronidazole (500 mg PO bid for 14 d [$4/course]) may be considered if the community prevalence and individual risk of gonorrhea is low. Increasing fluoroquinolone resistance in gonococcal isolates necessitates treatment regimens that do not rely on fluoroquinolones for gonococcal coverage. Tests for gonorrhea must be performed prior to instituting therapy and if positive, the patient managed without fluoroquinolone therapy.For more information see, Recent Updates From the Medical Literature.
Patients with suspected cervicitis must be treated for both gonococcal and chlamydial infection because co-infection exists in up to 40% of cases. Use cefixime 400 mg orally once plus azithromycin 1 g orally once ($39/1 g). Although the manufacturer of cefixime discontinued the drug in 2002, Lupin Limited began to re-manufacture cefixime in 2004. Supplies are still limited. As an alternative to the above regimen, 2 g of azithromycin in a single dose covers both gonococcal and chlamydial cervicitis; however, an increased incidence of gastrointestinal side effects exists. The single-dose regimens for chlamydia are recommended over the traditional 10-day doxycycline treatment because overall compliance with a 10-day regimen is dismal. In one survey, of 386 women given 10-day prescriptions of doxycycline for PID, only a third reported compliance. Of the rest, 41% stopped their medication after 4 days, and the remainder never filled their prescriptions.
Note that none of these therapies except for an extended course of doxycycline (14-d bid) adequately covers syphilis. Although the incidence of syphilis has diminished greatly in the United States, it has reemerged in recent years. A quarter of these cases occur in HIV-positive patients. In patients diagnosed with a sexually transmitted disease, consider obtaining syphilis serologic tests (eg, rapid plasma reagin [RPR], venereal disease research laboratory [VDRL]). Patients should have adequate follow-up in the event serologic testing demonstrates the disease. In 1998, the CDC changed its recommended treatment of primary syphilis from a single dose to 3 weekly doses of benzathine penicillin ($112/2.4 mU IM). In cases of neurosyphilis, recommended treatment is 2 weeks of inpatient IV penicillin (4 mU IV q4h).
Sexual assault
Give cefixime (400 mg single dose), plus azithromycin (1 g oral sachet once; $39), plus HBIG (0.06 mL/kg IM) if not vaccinated, plus Plan B or Ovral (2 tablets immediately and 2 tablets in 12 h). Consider promethazine for nausea.
Give cefixime (400 mg single dose), plus azithromycin (1 g oral sachet once; $39), plus HBIG (0.06 mL/kg IM) if not vaccinated, plus Plan B or Ovral (2 tablets immediately and 2 tablets in 12 h). Consider promethazine for nausea.
Wounds, Bites, and High-Risk Exposures
The most important aspect of wound management in overall reduction of infection rate is mechanical cleansing. When possible, perform this using high-pressure irrigation (eg, 35 mL syringe and <19-gauge href="javascript:showcontent(">53,54 Soap and water may be equally effective in out-of-hospital settings. Noncontaminated facial and scalp lacerations do not need irrigation.55 Use a minimum of 200 mL; higher volumes are more effective. Avoid peroxide, Betadine, and chlorhexidine, which damage viable tissue.56 Half-strength peroxide swabbed on sutured wounds every 6 hours will reduce scarring from blood clot.57 Antibiotic ointment (eg, bacitracin) has been shown to reduce incidence of wound infections.58
Classify wounds as tetanus prone or not. Tetanus-prone wounds are deep, dirty, devitalized, or older than 6 hours. About 60 cases of tetanus occur in the United States per year, mostly in elderly patients whose immunity has waned. For tetanus-prone wounds, if the patient is not immunized (ie, <3>3 doses but last dose given >5 y prior), give active immunization only. For non–tetanus-prone wounds, give active immunization only, using 10 years as a cutoff. Active immunization is a combination tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap, 0.5 mL IM). This represents an updated recommendation by the CDC in 2006, and should be given to patients aged 11-64.59 In children younger than 8 years, give diphtheria, pertussis, and tetanus (DPT) instead. Passive immunization is tetanus immune globulin (TIG) 500 units deep IM.
The literature provides 5 indications for prophylactic antibiotics in wounds. These include intraoral lacerations, complicated human or dog bites, cat bites, and foot puncture wounds. Although commonly used, little evidence exists that prophylactic antibiotics are useful for patients with significant comorbidities (eg, diabetes mellitus [DM]), cirrhosis, advanced age, immunosuppression).57 Prophylactic antibiotics are not indicated for missile wounds.60 When indicated, use an antibiotic with coverage for staphylococci as well as one that covers those species unique to the type of wound.
In high-risk wounds (eg, hand wound, those in immunocompromised patients, cat bite, wound in areas of reduced vascularity), give the initial dose of prophylactic antibiotic intravenously within 3 hours of injury for best efficacy. For bites, use a BL/BLI antibiotic for the initial IV dose (eg, ticarcillin/clavulanate 3.1 g or piperacillin/tazobactam 3.375 g).
A common wound encountered in the emergency department is the through-the-shoe puncture wound. This presents a 10% risk for infection, 90% from pseudomonads in wounds involving rubber-soled shoes. These infections can progress to osteomyelitis.46 Antibiotic prophylaxis is controversial.61 Ciprofloxacin has been suggested; however, it is too expensive for universal use and is contraindicated in children. An alternative is TMP-SMZ, which has mild activity against pseudomonads and other skin flora, and is inexpensive. All patients need instructions on self-wound checks and follow-up.
Prophylactic antibiotics are used to prevent, not treat, an infection, so therapy duration can be shortened. However, no consensus exists as to exact duration needed. The Sanford Guide to Antimicrobial Therapy suggests 3 days if no wound inflammation exists, or 3 days past the clearance of wound inflammation. Alternatively, give a 2-day course ending with a formal wound check. If the wound is infected at the time of reexamination, antibiotics can be continued.
The most important aspect of wound management in overall reduction of infection rate is mechanical cleansing. When possible, perform this using high-pressure irrigation (eg, 35 mL syringe and <19-gauge href="javascript:showcontent(">53,54 Soap and water may be equally effective in out-of-hospital settings. Noncontaminated facial and scalp lacerations do not need irrigation.55 Use a minimum of 200 mL; higher volumes are more effective. Avoid peroxide, Betadine, and chlorhexidine, which damage viable tissue.56 Half-strength peroxide swabbed on sutured wounds every 6 hours will reduce scarring from blood clot.57 Antibiotic ointment (eg, bacitracin) has been shown to reduce incidence of wound infections.58
Classify wounds as tetanus prone or not. Tetanus-prone wounds are deep, dirty, devitalized, or older than 6 hours. About 60 cases of tetanus occur in the United States per year, mostly in elderly patients whose immunity has waned. For tetanus-prone wounds, if the patient is not immunized (ie, <3>3 doses but last dose given >5 y prior), give active immunization only. For non–tetanus-prone wounds, give active immunization only, using 10 years as a cutoff. Active immunization is a combination tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap, 0.5 mL IM). This represents an updated recommendation by the CDC in 2006, and should be given to patients aged 11-64.59 In children younger than 8 years, give diphtheria, pertussis, and tetanus (DPT) instead. Passive immunization is tetanus immune globulin (TIG) 500 units deep IM.
The literature provides 5 indications for prophylactic antibiotics in wounds. These include intraoral lacerations, complicated human or dog bites, cat bites, and foot puncture wounds. Although commonly used, little evidence exists that prophylactic antibiotics are useful for patients with significant comorbidities (eg, diabetes mellitus [DM]), cirrhosis, advanced age, immunosuppression).57 Prophylactic antibiotics are not indicated for missile wounds.60 When indicated, use an antibiotic with coverage for staphylococci as well as one that covers those species unique to the type of wound.
In high-risk wounds (eg, hand wound, those in immunocompromised patients, cat bite, wound in areas of reduced vascularity), give the initial dose of prophylactic antibiotic intravenously within 3 hours of injury for best efficacy. For bites, use a BL/BLI antibiotic for the initial IV dose (eg, ticarcillin/clavulanate 3.1 g or piperacillin/tazobactam 3.375 g).
A common wound encountered in the emergency department is the through-the-shoe puncture wound. This presents a 10% risk for infection, 90% from pseudomonads in wounds involving rubber-soled shoes. These infections can progress to osteomyelitis.46 Antibiotic prophylaxis is controversial.61 Ciprofloxacin has been suggested; however, it is too expensive for universal use and is contraindicated in children. An alternative is TMP-SMZ, which has mild activity against pseudomonads and other skin flora, and is inexpensive. All patients need instructions on self-wound checks and follow-up.
Prophylactic antibiotics are used to prevent, not treat, an infection, so therapy duration can be shortened. However, no consensus exists as to exact duration needed. The Sanford Guide to Antimicrobial Therapy suggests 3 days if no wound inflammation exists, or 3 days past the clearance of wound inflammation. Alternatively, give a 2-day course ending with a formal wound check. If the wound is infected at the time of reexamination, antibiotics can be continued.
Skin infections
Cephalexin is recommended by many (500 mg qid, $4/10-d course). For convenience, it may also be dosed 2 or 3 times daily, instead of the traditional 4 times daily (manufacturer's insert). Alternatives to cephalexin include dicloxacillin (250 mg qid, $22/10-d course), TMP-SMZ ($4/10 d), and doxycycline ($4/10d). The latter two may provide additional coverage against CA-MRSA species in regions where this has become endemic.
Cephalexin is recommended by many (500 mg qid, $4/10-d course). For convenience, it may also be dosed 2 or 3 times daily, instead of the traditional 4 times daily (manufacturer's insert). Alternatives to cephalexin include dicloxacillin (250 mg qid, $22/10-d course), TMP-SMZ ($4/10 d), and doxycycline ($4/10d). The latter two may provide additional coverage against CA-MRSA species in regions where this has become endemic.
Bite wounds
Cats cause only 5% of bites presenting to emergency departments, but these bites are associated with a high risk of infection (80%). Most infections (80%) are caused by Pasteurella multocida, a pleomorphic gram-negative rod. For cat bites, amoxicillin/clavulanate 500 mg bid ($17/d) is recommended. Less costly alternatives include doxycycline 100 mg bid, penicillin V 500 mg bid/qid, and TMP-SMZ bid (all $4/course).
Dog bites cause the majority (90%) of bites presenting to emergency departments but are associated with a low risk of infection (5%). Dog maulings in the United States kill 18 persons annually; 60% occur in children younger than 11 years. In the United States, about 2% of the population is bitten annually; 800,000 people require medical attention.62 Infections are usually polymicrobial. Antibiotic prophylaxis has no proven benefit. However, the Sanford Guide to Antimicrobial Therapy suggests amoxicillin/clavulanate as above. Less costly alternatives include clindamycin 150 mg qid plus TMP-SMZ double strength (DS) bid. Treat patients who have been bitten by a dog and who have had a splenectomy with prophylactic penicillin due to increased risk of sepsis and death due to the rare bacterial species Capnocytophaga canimorsus.
Human bites comprise 3% of bites presenting to emergency departments and are associated with a 50% infection rate. Many human bites are clenched fist injuries, which are particularly high infection risks. Amoxicillin/clavulanate is recommended as above. The Sanford Guide to Antimicrobial Therapy suggests 5 days of prophylaxis. Patients discharged from the emergency department should have a follow-up check in 24 hours. Consider passive immunization for hepatitis B with immune globulin (HBIG) 0.06 mL/kg IM.
Cats cause only 5% of bites presenting to emergency departments, but these bites are associated with a high risk of infection (80%). Most infections (80%) are caused by Pasteurella multocida, a pleomorphic gram-negative rod. For cat bites, amoxicillin/clavulanate 500 mg bid ($17/d) is recommended. Less costly alternatives include doxycycline 100 mg bid, penicillin V 500 mg bid/qid, and TMP-SMZ bid (all $4/course).
Dog bites cause the majority (90%) of bites presenting to emergency departments but are associated with a low risk of infection (5%). Dog maulings in the United States kill 18 persons annually; 60% occur in children younger than 11 years. In the United States, about 2% of the population is bitten annually; 800,000 people require medical attention.62 Infections are usually polymicrobial. Antibiotic prophylaxis has no proven benefit. However, the Sanford Guide to Antimicrobial Therapy suggests amoxicillin/clavulanate as above. Less costly alternatives include clindamycin 150 mg qid plus TMP-SMZ double strength (DS) bid. Treat patients who have been bitten by a dog and who have had a splenectomy with prophylactic penicillin due to increased risk of sepsis and death due to the rare bacterial species Capnocytophaga canimorsus.
Human bites comprise 3% of bites presenting to emergency departments and are associated with a 50% infection rate. Many human bites are clenched fist injuries, which are particularly high infection risks. Amoxicillin/clavulanate is recommended as above. The Sanford Guide to Antimicrobial Therapy suggests 5 days of prophylaxis. Patients discharged from the emergency department should have a follow-up check in 24 hours. Consider passive immunization for hepatitis B with immune globulin (HBIG) 0.06 mL/kg IM.
Rabies
An average of one human rabies case is reported annually in the United States, mostly in immigrants. In nonimmigrants, human rabies is almost entirely due to exposure to infected bats. Other high-risk animals include skunks, raccoons, foxes, and wild carnivores. Treat patients with bites from all of these animals for rabies. Only a fraction of rabid animals are domesticated, and nearly half of all rabid animals are raccoons.63 Interestingly, only one human rabies case from raccoons has ever been reported.64 Low-risk animals include dogs and cats.
Because of pet vaccination, an observed 8,000 canine cases of rabies in 1946 dropped to 128 in 1988. Do not treat patients with these bites unless a rabid animal is suspected. Other recommendations include a 10-day observation of pets and killing of all wild animals for immediate examination of brain tissue using fluorescent antibodies. Currently, zero-risk animals include cows, pigs, rabbits, rats, squirrels, mice, hamsters, gerbils, and nutria.
Treatment includes passive and active immunization. Cost exceeds $1,500 per case.65 This consists of human rabies immune globulin (HRIG, $750/100 kg dosing) 20 IU/kg, half of the dose infiltrated around the wound and half IM, and human diploid cell vaccine (HDCV, $202/dose) 1 mL IM at a site distant from the immunoglobulin on days 0, 3, 7, 14, and 28.66,67
An average of one human rabies case is reported annually in the United States, mostly in immigrants. In nonimmigrants, human rabies is almost entirely due to exposure to infected bats. Other high-risk animals include skunks, raccoons, foxes, and wild carnivores. Treat patients with bites from all of these animals for rabies. Only a fraction of rabid animals are domesticated, and nearly half of all rabid animals are raccoons.63 Interestingly, only one human rabies case from raccoons has ever been reported.64 Low-risk animals include dogs and cats.
Because of pet vaccination, an observed 8,000 canine cases of rabies in 1946 dropped to 128 in 1988. Do not treat patients with these bites unless a rabid animal is suspected. Other recommendations include a 10-day observation of pets and killing of all wild animals for immediate examination of brain tissue using fluorescent antibodies. Currently, zero-risk animals include cows, pigs, rabbits, rats, squirrels, mice, hamsters, gerbils, and nutria.
Treatment includes passive and active immunization. Cost exceeds $1,500 per case.65 This consists of human rabies immune globulin (HRIG, $750/100 kg dosing) 20 IU/kg, half of the dose infiltrated around the wound and half IM, and human diploid cell vaccine (HDCV, $202/dose) 1 mL IM at a site distant from the immunoglobulin on days 0, 3, 7, 14, and 28.66,67
HIV—Post-exposure prophylaxis
In high-risk source patients (eg, known symptomatic HIV infection, AIDS, acute seroconversion, known high viral load) or exposures (eg, large-bore hollow needle, deep puncture, visible blood on device, needle used in patient's artery or vein), the recommended 2-drug regimen (ie, zidovudine [ZDV] plus lamivudine [3TC]; or 3TC and stavudine [d4T]; or d4T and didanosine [ddI]) should begin within 60 minutes of exposure. If the source is high risk and there was a high-risk exposure, a 3-drug regimen is recommended.68 Other retroviral agents can be substituted for these agents. However, nevirapine is not recommended because of several reported cases of life-threatening hepatotoxicity occurring during prophylaxis. Also give HBIG (0.06 mL/kg IM) for those not vaccinated against hepatitis B.
Mucocutaneous exposures should receive 2 drugs prophylactically in cases involving high-risk source patients or large volumes of blood. Postexposure prophylaxis is not recommended (but may be considered) when the source is unknown or when the source patient's HIV status is unknown.
For questions not answered by this section, the US Department of Health and Human Services has a toll-free 24-hour number available to clinicians for advice on postexposure prophylaxis: (888) 448-4911.
In high-risk source patients (eg, known symptomatic HIV infection, AIDS, acute seroconversion, known high viral load) or exposures (eg, large-bore hollow needle, deep puncture, visible blood on device, needle used in patient's artery or vein), the recommended 2-drug regimen (ie, zidovudine [ZDV] plus lamivudine [3TC]; or 3TC and stavudine [d4T]; or d4T and didanosine [ddI]) should begin within 60 minutes of exposure. If the source is high risk and there was a high-risk exposure, a 3-drug regimen is recommended.68 Other retroviral agents can be substituted for these agents. However, nevirapine is not recommended because of several reported cases of life-threatening hepatotoxicity occurring during prophylaxis. Also give HBIG (0.06 mL/kg IM) for those not vaccinated against hepatitis B.
Mucocutaneous exposures should receive 2 drugs prophylactically in cases involving high-risk source patients or large volumes of blood. Postexposure prophylaxis is not recommended (but may be considered) when the source is unknown or when the source patient's HIV status is unknown.
For questions not answered by this section, the US Department of Health and Human Services has a toll-free 24-hour number available to clinicians for advice on postexposure prophylaxis: (888) 448-4911.
Meningococcus
Administer ciprofloxacin 750 mg once by mouth. Pregnant women and children can receive ceftriaxone 125 mg IM once. One study suggests that azithromycin may be effective for chemoprophylaxis as well.69 For repeated exposures in high-risk occupations, a conjugated tetravalent meningococcal vaccine is available.
Positive tuberculin skin test
See paragraph on tuberculosis in this text for more detail. Isoniazid 300 mg daily for 6 months (or 900 mg twice weekly for 12 mo) reduces lifetime risk of death from TB from over 6% to nearly zero. A recently validated alternative is daily rifampin and pyrazinamide taken for 2 months.70
Administer ciprofloxacin 750 mg once by mouth. Pregnant women and children can receive ceftriaxone 125 mg IM once. One study suggests that azithromycin may be effective for chemoprophylaxis as well.69 For repeated exposures in high-risk occupations, a conjugated tetravalent meningococcal vaccine is available.
Positive tuberculin skin test
See paragraph on tuberculosis in this text for more detail. Isoniazid 300 mg daily for 6 months (or 900 mg twice weekly for 12 mo) reduces lifetime risk of death from TB from over 6% to nearly zero. A recently validated alternative is daily rifampin and pyrazinamide taken for 2 months.70
Keywords
antibiotic therapy, antibiotics in the ED, antibiotics in the emergency department, microbial infections, bacterial infections, treatment of bacterial infections, empiric antibiotic therapy, golden rules of antibiotic use, broad-spectrum antibiotics, antimicrobial therapy, cephalosporins, anaerobic coverage, pseudomonal coverage, antibiotic-resistant gram-positive cocci, MRSA, methicillin-resistant Staphylococcus aureus, gram-negative sepsis, bacterial meningitis, pneumonia, respiratory infections, bronchitis, influenza, sinusitis, otitis media, pharyngitis, urinary tract infections, vaginal infections, sexual assault, bites, wounds, rabies
Acknowledgments
The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, Diana Brainard, MD, and Daniel Hayes, PharmD, to the development and writing of this article.
antibiotic therapy, antibiotics in the ED, antibiotics in the emergency department, microbial infections, bacterial infections, treatment of bacterial infections, empiric antibiotic therapy, golden rules of antibiotic use, broad-spectrum antibiotics, antimicrobial therapy, cephalosporins, anaerobic coverage, pseudomonal coverage, antibiotic-resistant gram-positive cocci, MRSA, methicillin-resistant Staphylococcus aureus, gram-negative sepsis, bacterial meningitis, pneumonia, respiratory infections, bronchitis, influenza, sinusitis, otitis media, pharyngitis, urinary tract infections, vaginal infections, sexual assault, bites, wounds, rabies
Acknowledgments
The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, Diana Brainard, MD, and Daniel Hayes, PharmD, to the development and writing of this article.
