Antibiotics - A Review of ED Use
- Author: Katherine M Hiller, MD; Chief
Editor: Rick Kulkarni, MD more...
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.[1]
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.[2, 3]
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.
Key therapy
recommendations taken from this article can be found in the image below.
Antibiotics
Guidelines Summary.
Recent Updates From the Medical
Literature
In August 2012, the CDC announced
changes to 2010 sexually transmitted disease guidelines for gonorrhea
treatment. The Gonococcal Isolate Surveillance Project (GISP) described a
decline in cefixime susceptibility among urethral N gonorrhoeae isolates in the
United States during 2006-2011. Because of cefixime’s lower susceptibility, new
guidelines were issued that no longer recommend oral cephalosporins for
first-line gonococcal infection treatment.[94]
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.[4] 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.[5, 6, 7, 8]
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.[9] 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.[10] 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.[11] Additionally, older antibiotics, such as
sulfamethoxazole/trimethoprim and doxycycline, may play a role in treatment of
MRSA.[12]
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.[13]
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 pyelonephritis[14]
, cellulitis[15] , and pneumonia[16] . 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 (
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.[17] 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.[18, 19] 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).
Anaerobic Coverage
Antibiotics with good anaerobic
coverage include metronidazole (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.[11] 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 mm Hg or the alveolar
arterial (A-a) gradient is >35. Note that the mortality rate is high even
with therapy: 10-20% in patients without hypoxia and 20-40% in patients with
hypoxia.[20]
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.[21] 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.[22] 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.[23]
Early steroid treatment for
bacterial meningitis may improve outcomes. A recent meta-analysis determined
there was no treatment benefit with adjunctive steroids in bacterial
meningitis.[24] If considering adjunctive steroid use,
dexamethasone should be given concurrently with the first dose of antibiotics.
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