Special Feature

Quinolone Wars in the ED: Which Bomb for Which Battle?

By Michael Felz, MD

Introduction

Fluoroquinolones (FQs) are precise and powerful agents against infectious diseases. By inhibition of DNA gyrase leading to rapid bactericidal activity, these drugs are "smart bombs" of great value in fighting an array of gram-positive and gram-negative bacterial pathogens. Keeping current on these agents is an ongoing process, due to the release of new drugs and withdrawals of five agents (trova-, tema-, grepa-, spar-, and lome- floxacin) due to unanticipated side effects dating from 1992. Such balance between efficacy and safety may confound ED physicians who depend upon current scientific data for daily decisions, particularly in times of therapeutic uncertainty in penicillin- and macrolide-resistant pneumococcal strains and ever-changing gram-negative resistance. Pharmaceutical representatives contribute to the "decision war" by presenting physicians with evidence-based, but potentially biased, information about each drug. Sadly, it is not realistic to expect any single FQ to prove suitable for all infectious syndromes. This review is an update on the three major battle zones where FQs are central in ED management — community-acquired pneumonia (CAP), urinary tract infection (UTI), and skin and soft tissue infection (SSTI). It is imperative that physicians be judicious in selecting the right bombs for each battle.

Community-Acquired Pneumonia

The main culture-proven pathogens demonstrated in ambulatory CAP patients are Streptococcus pneumoniae (most frequent), Haemophilus influenzae, and Moraxella catarrhalis, as well as atypicals, such as Legionella pneumophila, Chlamydia pneumoniae, and Mycoplasma pneumoniae. Initial antibiotic considerations could include an oral macrolide, amoxicillin-clavulanate, or doxycycline, depending upon preexisting conditions and local bacterial resistance patterns. Yet, current guidelines emphasize the sustained reliability of three respiratory FQs — levofloxacin (levo), gatifloxacin (gati), and moxifloxacin (moxi) — for initial therapy in ambulatory patients assessed carefully for unusual risk factors.1 As of this writing, levo, gati, and moxi have maintained activity against more than 98% of S. pneumoniae strains in the United States, including penicillin-resistant isolates, and clinical trials have demonstrated equivalence or superiority to other regimens in widespread use. While levo has greater prescribing volume since licensure in 1996, gati and moxi have recent data suggesting superior in vitro anti-pneumococcal activity. Nonetheless, all three FQs have achieved comparable and commendable clinical success in CAP management.2 For example, in 108 CAP patients identified with pneumococcal bacteremia, 98 (90.7%) of these cases were treated successfully with levo, including 11 (91.7%) of 12 infected with penicillin- or macrolide-resistant strains; one would predict from in-vitro data that gati and moxi would be efficacious as well.3 These three respiratory FQs, then, are probably equivalent in efficacy against the common pathogens (and atypicals) in CAP and can be recommended with equal enthusiasm.4 Usual doses are: levo, 500 mg/d; gati, 400 mg/d; and moxi, 400 mg/d. No robust data exist as to optimal duration of CAP therapy, but typical regimens are for 7-10 days.5 In the near future, stay tuned for gemifloxacin to enter the fray as well, with enhanced activity against multi-drug-resistant pneumococcus.

Urinary Tract Infections

Treatment for UTI targets gram-negative organisms. The most common uropathogen in most series (and at our institution) is by far Escherichia coli, followed by organisms of the Klebsiella, Proteus, Enterobacter, Serratia, Enterococcus, and Pseudomonas species.

Clinical efficacy against most of these pathogens ranges from 80-100% for two of the FQs—levo and gati—in published trials and reviews.6 Moxi has performed less reliably in UTI treatment due to suboptimal concentration in urine. In addition, an older-generation quinolone — ciprofloxacin (cipro) — has retained highly effective performance in UTI treatment based upon 20 years of clinical and microbiologic evidence. Whether the illness is cystitis or pyelonephritis, levo and gati, along with cipro, are the ED physician’s tested weapons for empiric UTI management requiring quinolones. Oral alternatives remain beta-lactams, trimethoprim/sulfamethoxasole, and (for cystitis only) nitrofurantoin.

A nagging dilemma is unpredictable resistance among Pseudomonas isolates. National monitoring by 26 institutions in the Tracking Resistance in the United States Today (TRUST) Microbiology Network documented susceptibilities for 404 Pseudomonas isolates in 2002 to be 73.5, 73, and 71% for cipro, levo, and gati, respectively.7 (In 2003, our institution documented 64, 63, and 71%, respectively). Indwelling catheters, diabetes mellitus, and recent Pseudomonas infections, or intensive care unit admissions heighten the risk for Pseudomonas. Ill patients with such complicated UTIs often require hospitalization for therapy with parenteral cephalosporins (such as cefepime), aminoglycosides, imipenem, or piperacillin/tazobactam.

The prudent weapons, then, against uncomplicated cystitis and pyelonephritis, would include levo, gati, or cipro, but probably not moxi. Usual doses are: levo, 250-750 mg/d; gati, 400 mg/d; or cipro, 500-1000 mg/d depending upon illness severity and location of infection (lower vs upper tract). Recent evidence supports three-day regimens for cystitis and five-to-seven-day regimens for ambulatory pyelonephritis.

Skin and Soft Tissue Infections

SSTIs frequently encountered in the ED include cellulitis, impetigo, folliculitis, furuncles, dermal abscesses, and wound infections. Most of them are due to Staphylococcus aureus, Streptococcus pyogenes, or both. Traditional therapy has utilized oral amoxcillin/clavulanate, dicloxacillin, macrolides, or cephalosporins. Clinical studies have supported the efficacy of levo in SSTI.8 Based upon additional trials, the Food and Drug Administration recently expanded indications for two additional FQs: moxi (in 2001) and gati (in 2002) to include uncomplicated SSTIs, with demonstrated clinical cure rates of 90 and 91%, respectively.9 Recommended dosages are: levo, 500-750 mg/d; moxi, 400 mg/d; and gati, 400 mg/d, for 7 days. Those three FQs, then, are effective — and perhaps little known — weapons for the ED physician in management of SSTIs.

Summary

ED clinicians managing CAP, UTI, and SSTI in practice must consider a panorama of clinical, microbiologic, and epidemiologic variables. FQs are precise and predictable performers in those three war zones and deserve consideration as first-line agents or when non-FQ regimens are less desirable or proven to have failed. The appeal of their efficacy must be weighed against concerns of overuse where cheaper and otherwise acceptable treatments may suffice, especially in this era of emerging antibiotic resistance. The table is a summary of current indications for each drug in those three war zones.

Table.
Usefulness of Selected Fluoroquinolones
in Common Infections

Dr. Felz, Associate Professor, Department of Family Medicine, Medical College of Georgia, Augusta, is on the Editorial Board of Emergency Medicine Alert.

References

1. Mandell LA, et al. Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis 2003;37: 1405-1433.

2. File TM. Current challenges in the treatment of community-acquired pneumonia. Clin Infect Dis 2004;38: S1-S4.

3. Kahn JB. Cumulative clinical trial experience with levofloxacin for patients with community-acquired pneumonia-associated pneumococcal bacteremia. Clin Infect Dis 2004;38:S34-42.

4. Abramovicz M. Drugs for pneumonia. Medical Letter 2003;1:83-88.

5. Oliphant CM, et al. Quinolones: A comprehensive review. Am Fam Physician 2002;65:455-464.

6. Hooton TM. The current management strategies for community-acquired urinary tract infection. Infect Dis Clin of North Am 2003;17:303-332.

7. Karlowsky JA. Susceptibility to fluoroquinolones among commonly isolated gram-negative bacilli in 2000; TRUST and TSN data for the US. Internat J Antimicrob Agents 2002;19:21-31.

8. Tarshis GA, et al. Once-daily gatifloxacin vs levofloxacin in treatment of uncomplicated skin and soft tissue infections: A double-blind, multicenter, randomized study. Antimicrob Agents Chemother 2001;8: 2358-2362.

9. Schweiger ES, et al. Novel antibacterial agents for skin and skin structure infections. J Am Acad Dermatol 2004;50:331-340.