Breakthrough pneumococcal meningitis in a patient treated with pristinamycin
Authors: F. Goldstein, J. Jonte, F. Mandel, A. Ben Ali
Journal: Clinical Microbiology and Infection (2006)

We read with interest the paper in CMI by Hsueh et al. [1Hsueh PR Shyr JM Wu JJ Changes in macrolide resistance among respiratory pathogens after decreased erythromycin consumption in Taiwan.Clin Microbiol Infect. 2006; 12: 296-298Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar] concerning increasing resistance to macrolides in Streptococcus pneumoniae despite a > 50% decrease in macrolide consumption. We would like to stress the importance of possible clinical therapeutic failures caused by macrolide-resistant S. pneumoniae in patients treated with distantly related compounds such as pristinamycin. Pristinamycin has been used widely in France for nearly 50 years in the treatment of staphylococcal and streptococcal infections, including those caused by S. pneumoniae and strains resistant to macrolides or related compounds [2Tremolieres F Mayaud C Mouton Y et al.Efficacy and safety of pristinamycin vs. amoxicillin in community‐acquired pneumonia in adults.Pathol Biol. 2005; 53: 503-510Crossref PubMed Scopus (15) Google Scholar, 3Poirier R Pristinamycin in the treatment of acute communicable pneumopathies in adults.Presse Med. 1999; 28 (11): 13PubMed Google Scholar]. Since our report of the first macrolide-resistant S. pneumoniae in France [4Goldstein FW Dang Van A Bouanchaud DH Acar JF Increased resistance of Streptococcus pneumoniae to antibiotics and prevalence of their capsular serotypes.Pathol Biol. 1978; 26: 173-180PubMed Google Scholar], > 50% of all French S. pneumoniae isolates have become resistant to macrolides, which is the highest reported prevalence in the western world, although lower than that in south-east Asia. About 97% of these isolates are of the macrolides, lincosamides, streptogramins (MLSB) phenotype (E. Varron, personal communication). Despite this high prevalence, > 99% of the macrolide-resistant isolates remain fully susceptible to pristinamycin, with a mode MIC of 0.25–0.5 mg/L (25th Reunion Interdisciplinaire de Chimothérapie Anti-Infectieuse, Paris 2005, abstract 346/63p). Pristinamycin is a mixture of two compounds, A (Pri II) and B (Pri I), which are produced naturally by Streptomyces pristinaespiralis. Each compound is bacteriostatic, but their association is synergic and bactericidal. Despite resistance to compound B in MLSB-resistant streptococci, the synergic activity is not abolished, and this prevents the emergence of resistance to the combination. Quinupristin / dalfopristin, a semisynthetic derivative, has very similar activity [6Leclercq R Nantas L Soussy CJ Duval J Activity of RP 59500, a new parenteral semisynthetic streptogramin, against staphylococci with various mechanisms of resistance to macrolides‐lincosamides‐streptogramin antibiotics.J Antimicrob Chemother. 1992; 30: 67-75Crossref PubMed Scopus (70) Google Scholar]. However, diminished killing of these strains by pristinamycin has been observed in some studies [7Pankuch GA Jacobs MR Appelbaum PC MIC and time‐kill study of antipneumococcal activities of RPR 106972 (a new oral streptogramin), RP 59500 (quinupristin‐dalfopristin), pyostacine (RP 7293), penicillin G, cefotaxime, erythromycin, and clarithromycin against 10 penicillin‐susceptible and‐resistant pneumococci.Antimicrob Agents Chemother. 1996; 40: 2071-2074PubMed Google Scholar, 8Schlegel L Sissia G Fremaux A Geslin P Diminished killing of pneumococci by pristinamycin demonstrated by time‐kill studies.Antimicrob Agents Chemother. 2000; 44: 3246Crossref Scopus (1) Google Scholar], and we have observed the occurrence of a breakthrough case of meningitis caused by a macrolide-resistant S. pneumoniae in a patient treated with pristinamycin. A woman aged 55 years was hospitalised on 31 October 2005 with a clinical diagnosis of pneumonia. Upon examination, she had clear signs of meningitis, with cephalea, vomiting, neck stiffness, a vast array of neurological disorders, and a temperature of 39.5°C. During the previous 10 days, she had been treated with pristinamycin 2 × 1 g daily for an acute bronchitis. She had 10 600 white blood cells/mm3 with 92%neutrophils, and a C-reactive protein level of 113 mg/L. The cerebrospinal fluid contained 674 cells/mm3 with 95% neutrophils, and numerous S. pneumoniae cells were observed following Gram's stain. Two blood cultures were found to be positive in < 24 h. The isolates from the spinal fluid and blood were identical, with low-level resistance to β-lactams (MICs: penicillin G 0.75 mg/L; amoxycillin and cefotaxime 0.5 mg/L), resistance to tetracyclines, co-trimoxazole, macrolides and related compounds. The MIC of pristinamycin was 0.25 mg/L, with aminimum bactericidal concentration (MBC) of 2 mg/L. The strain belonged to serotype 19 A, which has emerged during recent years as being responsible for serious pneumococcal infections, including cases of meningitis (E. Varon, personal communication). The patient was treated with ceftriaxone 6 g/day and vancomycin 6 g/day for only 5 days because of acute renal failure. She also received 40 mg dexamethasone over the course of 4 days. By day 20 the patient had recovered. Conflicting results concerning the clinical efficacy of pristinamycin against macrolide-resistant S. pneumoniae with the MLSB phenotype have been reported [1Hsueh PR Shyr JM Wu JJ Changes in macrolide resistance among respiratory pathogens after decreased erythromycin consumption in Taiwan.Clin Microbiol Infect. 2006; 12: 296-298Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar, 9Burucoa C Pasdeloup T Chapon C Fauchere JL Robert R Failure of pristinamycin treatment in a case of pneumococcal pneumonia.Eur J Clin Microbiol Infect Dis. 1995; 14: 341-342Crossref PubMed Scopus (15) Google Scholar, 10Brevet‐Coupe F Guerin B Watine J Failure of pristinamycin treatment in a case of pneumonia caused by a streptogramin B‐type resistant pneumococcus.Scand J Infect Dis. 1998; 30: 419-420Crossref PubMed Scopus (5) Google Scholar]. In a double-blind study comparing the efficacy of pristinamycin with amoxycillin for the treatment of community-acquired pneumonia, pristinamycin was significantly less effective than amoxycillin (63.6% vs. 86.6%) in bacteraemic patients, with a 50%failure rate for macrolide-resistant S. pneumoniae [2Tremolieres F Mayaud C Mouton Y et al.Efficacy and safety of pristinamycin vs. amoxicillin in community‐acquired pneumonia in adults.Pathol Biol. 2005; 53: 503-510Crossref PubMed Scopus (15) Google Scholar]. Taken together, these data emphasise the need to reconsider the choice of pristinamycin or quinupristin/dalfopristin for the treatment of macrolide-resistant pneumococcal infections. We thank E. Varon, French Pneumococcal Reference Centre, for serotype determination and epidemiological data, and A. Ly for technical support.