Therapeutic failure and selection of resistance to quinolones in a case of pneumococcal pneumonia treated with ciprofloxacin

We have analyzed genetically three clinical isolates (3180, 3870, and 1244) of Streptococcus pneumoniae with high-level ciprofloxacin resistance. Isolates 3180 and 3870 were atypical because of their insolubility in deoxycholate. However, they hybridized specifically with pneumococcal autolysin and pneumolysin gene probes and have typical pneumococcal atpC and atpA gene sequences. Analysis of the complete sequences of the parC and gyrA genes revealed total variations of 8 and 8.7% (isolate 3180) and 7.4 and 3.6% (isolate 3870), respectively, compared to the wild-type strain R6 sequence. The variations observed between the sequences of R6 and isolate 1244 were less than 0.9%. The structure of the gyrA and parC genes from isolates 3180 and 3870 was organized in sequence blocks that show different levels of divergence, suggesting a pattern of recombination. These results are evidence for recombination at the fluoroquinolone target genes in clinical isolates of S. pneumoniae. The genetically related viridans group streptococci could act as a reservoir for fluoroquinolone resistance genes.

mentioning

confidence: 68%

Horizontal Transfer of parC and gyrA in Fluoroquinolone-Resistant Clinical Isolates of Streptococcus pneumoniae

Ferrándiz

Fenoll

Liñares

et al. 2000

“…A direct relation between the consumption of fluoroquinolones and an increase in the prevalence of resistance among S. pneumoniae isolates has been observed (8,27). In addition, the emergence of resistance during the treatment of pneumococcal pneumonia with fluoroquinolones has been described (9,37,38,44). Moreover, long-term CIP therapy of Pseudomonas aeruginosa infections caused the emergence of Cp r pneumococci that were colonizing a patient with bronchiectasis (12).…”

mentioning

confidence: 99%

Fitness of Streptococcus pneumoniae Fluoroquinolone-Resistant Strains with Topoisomerase IV Recombinant Genes

Balsalobre

Campa

2008

The low prevalence of ciprofloxacin-resistant (Cp r ) Streptococcus pneumoniae isolates carrying recombinant topoisomerase IV genes could be attributed to a fitness cost imposed by the horizontal transfer, which often implies the acquisition of larger-than-normal parE-parC intergenic regions. A study of the transcription of these genes and of the fitness cost for 24 isogenic Cp r strains was performed. Six first-level transformants were obtained either with PCR products containing the parC quinolone resistance-determining regions (QRDRs) of S. pneumoniae Cp r mutants with point mutations or with a PCR product that includes parE-QRDR-ant-parC-QRDR from a Cp r Streptococcus mitis isolate. The latter yielded two strains, T6 and T11, carrying parC-QRDR and parE-QRDR-ant-parC-QRDR, respectively. These first-level transformants were used as recipients in further transformations with the gyrA-QRDR PCR products to obtain 18 second-level transformants. In addition, strain Tr7 (which contains the GyrA E85K change) was used. Reverse transcription-PCR experiments showed that parE and parC were cotranscribed in R6, T6, and T11; and a single promoter located upstream of parE was identified in R6 by primer extension. The fitness of the transformants was estimated by pairwise competition with R6 in both one-cycle and two-cycle experiments. In the one-cycle experiments, most strains carrying the GyrA E85K change showed a fitness cost; the exception was recombinant T14. In the two-cycle experiments, a fitness cost was observed in most first-level transformants carrying the ParC changes S79F, S79Y, and D83Y and the GyrA E85K change; the exceptions were recombinants T6 and T11. The results suggest that there is no impediment due to a fitness cost for the spread of recombinant Cp r S. pneumoniae isolates, since some recombinants (T6, T11, and T14) exhibited an ability to compensate for the cost.

“…An increase in the rates of resistance to fluoroquinolones in both S. pneumoniae and VS would be expected as a consequence of the widespread use of these compounds. Prior fluoroquinolone administration is an important risk factor for the selection of resistant strains, as observed for respiratory tract infections caused by ciprofloxacin-resistant (Cip r ) (44) and levofloxacin-resistant (10, 54) S. pneumoniae isolates. Likewise, the emergence of Cip r isolates of VS in the blood of neutropenic cancer patients that received fluoroquinolone prophylaxis has been reported (23,55).…”

mentioning

confidence: 99%

Viridans Group Streptococci Are Donors in Horizontal Transfer of Topoisomerase IV Genes to Streptococcus pneumoniae

Balsalobre

Ferrándiz

Liñares

et al. 2003

100

A total of 46 ciprofloxacin-resistant (Cip r ) Streptococcus pneumoniae strains were isolated from 1991 to 2001 at the Hospital of Bellvitge. Five of these strains showed unexpectedly high rates of nucleotide variations in the quinolone resistance-determining regions (QRDRs) of their parC, parE, and gyrA genes. The nucleotide sequence of the full-length parC, parE, and gyrA genes of one of these isolates revealed a mosaic structure compatible with an interspecific recombination origin. Southern blot analysis and nucleotide sequence determinations showed the presence of an ant-like gene in the intergenic parE-parC regions of the S. pneumoniae Cip r isolates with high rates of variations in their parE and parC QRDRs. The ant-like gene was absent from typical S. pneumoniae strains, whereas it was present in the intergenic parE-parC regions of the viridans group streptococci (Streptococcus mitis and Streptococcus oralis). These results suggest that the viridans group streptococci are acting as donors in the horizontal transfer of fluoroquinolone resistance genes to S. pneumoniae.