Antibiotics in the ER
copied from E-medicine: Antibiotics: A Review of ED Use, Last Updated: October 5, 2004
Primarily geared toward adult medicine.

Penicillin Allergy

Penicillin allergy cross-reactivity with cephalosporins is a myth. Cross-reactivity between penicillins and cephalosporins is negligible, not 10-15% as commonly cited. However, if a patient has known anaphylaxis to penicillin, caution with cephalosporin use still is warranted.

Broad-spectrum antibiotics

These generally are chosen for empiric treatment of potentially life-threatening infections of unknown bacterial origin. Unfortunately, indiscriminate use has contributed to major antibiotic resistance. 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 ($8.20/g IV) and availability as an inexpensive oral treatment ($0.37/250 mg tablet).

In the United States, chloramphenicol may be considered an alternative in cases of penicillin-resistant bacteria or in 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 ($80.36/2 g), cefotaxime ($20.99/2 g), imipenem ($48.26/1 g),ticarcillin/clavulanate ($13.35/3.1 g), piperacillin/tazobactam ($14.80/3.375 g), and ampicillin/sulbactam ($12.88/3 g).

Second-generation cephalosporins

When in doubt, these 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 for presence of P aeruginosa (see Pseudomonal infections section). Examples of this class include cefmetazole, cefuroxime, cefoxitin, cefotetan, and cefamandole.

In certain hospitals, one second-generation cephalosporin may be less expensive than others due to special agreements with the supplier. Use the least expensive one. Relative to the cost of IV setup (>$100), however, cost differences between cephalosporins may be small. Published market prices to pharmacies for typical unit doses of these drugs are as follows: cefuroxime ($16.15/1.5 g), cefmetazole ($14.38/2 g, $6/2 g for bulk use from manufacturer), cefoxitin ($18.48/2 g), cefotetan ($22.32/2 g), cefamandole ($18.12/2 g). Despite variations in approved dosing intervals, half-lives for each of these is similar (0.8-2 h). If in doubt, a typical dosing is usually 1-2 g IV every 8 hours.

Antibiotics with good anaerobic coverage include metronidazole ($16.76/500 mg), clindamycin ($5.80/600 mg), and any beta-lactam/beta-lactamase inhibitor. For surgical and gynecologic cases in which a 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.

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 2 antibiotics with good gram-negative activity. Good choices include a third-generation cephalosporin or BL/BLI, plus aztreonam or an aminoglycoside. Examples of such coverage include ceftriaxone and gentamicin, ticarcillin/sulbactam and aztreonam, or cefmetazole and ciprofloxacin. Many possible drug combinations are acceptable as long as the antibiotics are not of the same class.

Pseudomonal infections

If serious pseudomonal infection is suspected, double coverage is recommended. Antibiotics with activity against P aeruginosa include ceftazidime, ticarcillin, aminoglycosides, imipenem, meropenem, levofloxacin, ciprofloxacin, and trovafloxacin. As for other antimicrobial regimens, the 2 agents chosen should be from different classes. For example, the combination of ticarcillin and gentamicin is good, whereas a combination of ceftazidime and imipenem is not. Piperacillin/tazobactam (Zosyn) 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 pseudomonads when using manufacturer-recommended doses of this drug, even when combined with a second agent.

Gram-positive cocci resistance

Multiple species of resistant gram-positive cocci warrant special consideration, particularly life-threatening infections when initially missing a resistant organism with antibiotic coverage may lead to death. For this reason, vancomycin ($15.60/g) should be used initially for presumed line sepsis to cover methicillin-resistant S aureus (MRSA), endocarditis, and meningitis (in most areas due to highly resistant pneumococcus). In these situations, vancomycin should be continued until cultures exclude MRSA and demonstrate sensitivity to other agents.

Bacterial meningitis

If meningitis is suspected, administer antibiotics without delay, prior to lumbar puncture. Antibiotics will not affect CSF cell counts for several hours, and more importantly, the patient will receive early treatment for a possibly rapid and fulminant disease. For immune-competent adults, use a third-generation cephalosporin alone (eg, ceftriaxone). 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 return.

About 5% of all pneumococci in the United States are now resistant, although rates are as high as 25% have been reported in some areas. Resistance observed in blood and CSF cultures from hospital inpatients is usually lower than resistance from other reservoir cultures (eg, nasopharyngeal swabs, sputum), probably because of antibiotic overuse in the outpatient setting

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 TB presents 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 should prompt rapid patient isolation in a negative-pressure room and initiation of a TB workup (eg, TB-specific blood cultures, sputum staining, culture). For further information, see Tuberculosis. If suspicion is high, isolating such patients even without overt symptoms is sometimes appropriate. Chest radiography 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 trimethoprim-sulfamethoxazole (TMP-SMZ) should be used to cover Pneumocystis carinii pneumonia (PCP). Additionally, a report by the National Institutes of Health/University of California concludes that prednisone 40 mg by mouth (PO) bid has been shown to reduce mortality in 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.

In patients who have community-acquired pneumonia and require hospitalization, a second-generation cephalosporin alone or with a macrolide (cefmetazole +/- azithromycin) is recommended. This covers the 7 most likely pathogens: S pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, S aureus, Mycoplasma pneumoniae, Legionella pneumoniae, and Chlamydia pneumoniae. Patients requiring admission to an intensive care unit should receive both a macrolide and a cephalosporin to cover L pneumoniae, now known to be among the top 4 microbial causes of community-acquired pneumonia. Institutionalized patients and those with known bronchiectasis (including patients with cystic fibrosis) should be treated for pseudomonads.

Sexually-transmitted diseases

Distinguish pelvic inflammatory disease (PID) from simple cervicitis. Though the causative bacterial species are similar, outpatient PID should not be treated with single-dose oral agents but with IM ceftriaxone ($10.71/250 mg) plus doxycycline for 14 days ($4/course). A recently advocated alternative to this regimen is ofloxacin 400 mg bid, metronidazole 500 mg bid, and doxycycline 100 mg bid, all for 14 days. However, this regimen is expensive ($122.44 cost to pharmacist for ofloxacin alone) and unlikely to be completed by patients.

Patients with suspected venereal disease should be treated for both gonococcal and chlamydial infection, as co-infection exists in up to 40% of cases. Use ciprofloxacin 500 mg orally once ($3.13/500 mg) or cefixime 400 mg orally once ($6.07/400 mg), plus azithromycin 1 g orally once ($24.16/g). Azithromycin is recommended over doxycycline despite its higher cost, because overall compliance with a 10-day doxycycline regimen is dismal. In a recent survey by Brookoff 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, with the exception of doxycycline (bid for 14 d), adequately covers the possibility of syphilis. All patients who are treated for venereal disease should have syphilis serology drawn (eg, rapid plasma reagin [RPR], venereal disease research laboratory [VDRL]) and should have follow-up in the event this demonstrates disease. Treatment of primary syphilis changed in 1998 from 1 to 2 weekly injections of benzathine penicillin (2.4 mU IM). For latent syphilis (> 1 year or unknown duration), treatment is 3 weekly injections of the same penicillin. For neurosyphilis, treatment is 2 weeks of inpatient IV penicillin (4 mU IV q4h).

Skin infections

Cephalexin is recommended by many, but it is expensive (500 mg qid; $39/10-d course). Alternatives include twice or thrice daily dosing (approved in skin infections according to manufacturer's insert), or dicloxacillin (250 mg qid; $15/10-d course), or TMP-SMZ ($4/10 d).