Relapse of Pneumococcal Pneumonia and Emergence of Quinolone Resistance
Abstract & Commentary
Synopsis: Four patients treated with levofloxacin for pneumococcal pneumonia had one or more relapses with levofloxacin-resistant isolates. In 5 of 6 relapses, the infecting strain was identical to the initial levofloxacin-susceptible strain by DNA typing.
Source: Anderson KD, et al. Emergence of levofloxacin-resistant pneumococci in immunocompromised adults after therapy for community-acquired pneumonia. Clin Infect Dis. 2003; 37:376-381.
Anderson and colleagues report the case histories of 4 patients with recurrent community-acquired pneumonia (CAP). All 4 patients had severe immunoglobulin deficiency, 3 due to X-linked agammaglobulinemia and 1 due to chronic lymphocytic anemia. All 4 patients presented initially with pneumococcal pneumonia caused by strains susceptible to levofloxacin. One of the 4 initial strains was resistant to penicillin (MIC = 2 mg/mL) and erythromycin, and the others were fully susceptible. All patients were treated with levofloxacin, and all responded to therapy. However, they had a total of 11 subsequent episodes of CAP; in 10 of these, the pneumococcus was isolated from blood or sputum. The subsequent episodes occurred 1-6 months after the first. Six of these episodes were caused by levofloxacin-resistant strains, and in 5, the resistant strain was identical by PFGE typing and serotyping to a susceptible strain previously isolated from the same patient. Each of the resistant isolates had amino acid substations in the quinolone-resistance determining region (QRDR) of the parC and gyrA genes.
Comment by Robert Muder, MD
With the rise in penicillin and erythromycin resistance among pneumococcal isolates, fluoroquinolones are frequently used as therapy for CAP. Fluoroquinolone monotherapy is a recommended option for the treatment of patients hospitalized with CAP.1 At present, the rate of quinolone resistance among US pneumococcal isolates is approximately 1%.2 Most clinical laboratories do not routinely perform quinolone susceptibility on pneumococcal isolates, and the NCCLS does not require it.
However, there are anecdotal reports of infection with quinolone-resistant pneumococci occurring in immunocompetent patients without any history of prior quinolone therapy.3 The patients reported by Anderson et al, in contrast, were likely to have been at considerable risk of infection due to quinolone-resistant pneumococci by virtue of significant immunoglobulin deficiency, recurrent episodes of pneumonia, and prior quinolone therapy. It is of note that infection with quinolone-resistant strains occurred as long as 6 months after the receipt of quinolones and that quinolone resistance in these patients was clearly associated with therapeutic failure.
Since quinolones are being increasingly prescribed for CAP, as well as for many other common infections, it is likely that the proportion of pneumococci resistant to this class of antimicrobial will gradually increase. I think it’s premature to abandon quinolones as first-line agents for CAP or to require mandatory quinolone susceptibility testing of all pneumococcal isolates. Rather, physicians treating patients with CAP should attempt to identify patients at risk of infection with quinolone-resistant pneumococci. Patients with recurrent or relapsing CAP and those who have received a quinolone within the preceding 6 months might more appropriately be treated with a beta-lactam/macrolide regimen. Sputum and blood cultures should be obtained from such patients prior to therapy, and any pneumococci isolated should be subjected to susceptibility testing to beta-lactams, macrolides, and quinolones.
One potential objection to this approach is the fairly high incidence of intermediate susceptibility and resistance to beta-lactams present in many areas. Of note, a recent international study of pneumococcal bacteremia found that non-meningeal infections responded to beta-lactam therapy regardless of in vitro beta-lactam susceptibility.4 Thus, the initial selection of a beta-lactam/macrolide regimen in patients at risk of infection with quinolone-resistant pneumococci appears to be the most appropriate option.
Dr. Muder is Hospital Epidemiologist Pittsburgh VA Medical Center Pittsburgh Section Editor, Hospital Epidemiology
References
1. Barlett JG, et al. Practice guidelines for the management of community acquired pneumonia in adults. Clin Infect Dis. 2000;31:347-382.
2. Doern GV, et al. Antimicrobial resistance among clinical isolates of Streptococcus pneumoniae in the United States 1999-2000, including a comparison of resistance rates since 1994-1995. Antimicrob Agents Chemother. 2001;45:1721-1729.
3. Davidson RD, et al. Resistance to levofloxacin and failure of treatment of pneumococcal pneumonia. N Engl J Med. 2002;346:747-750.
4. Yu VL, et al. An international prospective study of pneumococcal bacteremia: Correlation with in vitro resistance, antibiotics administered, and clinical outcome. Clin Infect Dis. 2003;37:230-237.
Four patients treated with levofloxacin for pneumococcal pneumonia had one or more relapses with levofloxacin-resistant isolates. In 5 of 6 relapses, the infecting strain was identical to the initial levofloxacin-susceptible strain by DNA typing.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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