Risk Factors Associated with Colonization by Pneumococci with Reduced Susceptibility to Fluoroquinolones in Adult Outpatients

Abstract

We developed a case-control study in order to identify risk factors associated with pharyngeal colonization by Streptococcus pneumoniae with reduced susceptibility to fluoroquinolones (ciprofloxacin MIC, >4 g/ml). A total of 400 patients were studied for colonization by quinolone-nonsusceptible S. pneumoniae (QNSP) isolates and risk factors for this colonization. Isolate susceptibility was determined by the agar dilution method. Forty patients were colonized by QNSP (case patients), and 360 patients were not colonized by QNSP (control patients). The MIC range of ciprofloxacin for QNSP isolates was 4 to 8 g/ml. No isolates were resistant to levofloxacin and moxifloxacin. Risk factors significantly associated with QNSP colonization, according to univariate analysis, were recent hospitalizations (odds ratio [OR], 3.43; 95% confidence interval [CI], 1.6 to 7.2; P < 0.01) and prior exposure to fluoroquinolones (OR, 6.04; 95% CI, 3.0 to 12.0; P < 0.01). Other factors such as chronic obstructive pulmonary disease (OR, 1.94; 95% CI; 0.7 to 5.0), prior exposure to penicillins (OR, 1,68; 95% CI, 0.8 to 3.3) and prior exposure to macrolides (OR 2; 95% CI, 0.6 to 6.2) were more frequent among patients colonized with QNSP, but there was no statistical significance. Multivariate analysis showed that exposure to fluoroquinolones was the only independent factor associated with colonization by QNSP (OR, 4.2; 95% CI, 1.8 to 9.4; P < 0.01). Throat colonization by QNSP is becoming frequent, though most of these isolates (all the isolates in this case) remain susceptible to newer fluoroquinolones. Previous treatment with fluoroquinolones seems to be the main risk factor associated with colonization by QNSP.The emergence and spread of drug-resistant Streptococcus pneumoniae are a major cause of concern in pneumococcal infection in recent years. More than 50% of isolates now found in several countries are resistant to penicillin (1,7,13,14,25), with Spain as one of the countries with the highest penicillin resistance rates (18). Among penicillin-resistant S. pneumoniae isolates, 60 to 80% are also resistant to cefuroxime, erythromycin, and clindamycin (13). Since the release in the late 1990s of newer fluoroquinolones (FQs) with enhanced activity against pneumococci, these drugs have been prescribed with increasing frequency for initial treatment of respiratory tract infections (10,22). FQ resistance rates remain low in S. pneumoniae in most countries (3,6,17), though higher resistance rates have been reported occasionally in some countries (9,12).Recent studies have shown that 30% of S. pneumoniae isolates for which the ciprofloxacin (CIP) MIC is 4 g/ml, and virtually all pneumococcal isolates for which the CIP MIC is Ͼ4 g/ml harbor one or more topoisomerases mutations (2), though not all these strains are levofloxacin (LEV) or moxifloxacin (MOX) resistant. Another recent study (16) showed that 59% of S. pneumoniae isolates intermediate for LEV (MIC of 2 g/ml) have a first-step mutation in parC. Thus, this group of strains with reduc...

Clinical Importance and Epidemiology of Quinolone Resistance

“…The known risk factors for infection or colonization by levofloxacin-resistant S. pneumoniae are previous exposure to quinolones, healthcare-associated infection, residence in a nursing home, presence of chronic obstructive pulmonary disease, and presence of cerebrovascular disease [ 75 , 76 , 77 ]. Fluoroquinolone resistance was not observed in a German study in spite of high usage of fluoroquinolones for the treatment of patients having community-acquired pneumonia [ 73 ].…”

In Vitro and In Vivo Antibacterial Activities of DC-159a, a New Fluoroquinolone

“…Quinolone antibacterials are beneficial for the empirical treatment of respiratory infections in the community because of their extended antibacterial spectra, including atypical pathogens, with preferable pharmacokinetic (PK) and safety profiles (30); however, several cases of treatment failure because of quinolone resistance-conferring mutations have been reported (5). Several risk factors existed in patients who were infected with quinolone-resistant mutants (11,13,29). It is well known that quinolone resistance was acquired in a stepwise fashion, and therefore, not only treatment for highly resistant variants but also prevention of the selection of first-step mutations should be considered in controlling resistance (21).…”

Bacteremic Pneumonia Caused by Extensively Drug-Resistant Streptococcus pneumoniae

“…The emergence and spread of drug-resistant S. pneumoniae have been major causes of concern related to pneumococcal infection in recent years (9). The emergence of antimicrobial resistance threatens the successful treatment of pneumococcal infections (14).…”

“…Vaccine escape of XDR pneumococci such as the one reported here poses significant therapeutic challenges. In addition, use of fluoroquinolones should be restricted in patients who are at increased risk of MDR pneumococcal infection, as prior use of fluoroquinolones was reported to be a significant risk factor for fluoroquinolone resistance among pneumococci (7,9).…”