Invasive pneumococcal infections in France: Changes from 2009 to 2021 in antibiotic resistance and serotype distribution of Streptococcus pneumoniae based on data from the French Regional Pneumococcal Observatories network.

OBJECTIVE: The 23 French Regional Pneumococcal Observatories (ORPs) analyzed antibiotic resistance and serotypes of Streptococcus pneumoniae strains isolated from invasive infections in France over a 12-year period. METHODS: Between 2009 and 2021, the ORPs analyzed 19,319 strains, including 1,965 in children and 17,354 in adults. Strains were assessed for their resistance to penicillin G, amoxicillin and cefotaxime. Serotypes were identified in collaboration with the National Reference Centre. RESULTS: During this period, the number of strains collected yearly decreased significantly. The decrease was particularly pronounced up until 2013, especially in children (-61.0%). However, penicillin non-susceptible strains (PNSPs) increased in children (24.7% in 2009 vs 45.0% in 2021, p < 0.0001) and in adults (27.1% in 2009 vs 31.3% in 2021, p < 0.05), as well as resistance (I + R) to amoxicillin (children: 12.5% in 2009 vs 19.4% in 2021, p < 0.05; adults: 13.4% in 2009 vs 14.5% in 2021, NS) and resistance (I + R) to cefotaxime (children: 8.0% in 2009 vs 13.1% in 2021, p < 0.05; adults: 7.1% in 2009 vs 11.9% in 2021, p < 0.0001). All in all, the proportion of strains belonging to serotypes present in the PCV13 vaccine has fallen sharply, from 64.8% in 2009 to 23.6 % in 2021. At the same time, serotypes such as 8, 10A, 11A, 15B/C and 9N, not included in PCV13, were increasing. CONCLUSION: During the study period, data collected by the network highlighted an increase of invasive PNSPs in children and non-vaccine serotypes. Surveillance of resistance and serotypes remains instrumental, particularly to monitor the evolution of vaccine efficacy.

Intrapartum group B Streptococcus screening in the labor ward by Xpert® GBS real-time PCR.

Group B Streptococcus (GBS) is the leading cause of neonatal infections in industrialized countries. Intrapartum antibiotic prophylaxis (IAP) given to colonized parturients is a key step for the prevention of neonatal early-onset infection. We compared the performances of Xpert® GBS polymerase chain reaction (PCR) (Cepheid, Sunnyvale, CA, USA) as a point-of-care system in labor wards to standard culture for intrapartum GBS detection. Pregnant women with a GBS-positive antenatal screening were prospectively included. A vaginal double swab was collected at the time of delivery for point-of-care Xpert® GBS PCR and GBS culture. A total of 565 pregnant women were included. Valid Xpert® GBS results were obtained for 488 (86.4%) women on the first attempt. Repeat testing improved the PCR success to 516 (91.3%) women. Among the 305 women positive for GBS by culture at delivery, only 238 (78.0%) were positive by Xpert® GBS PCR, cycle thresholds being correlated to culture quantification. Among 260 women negative for GBS culture, 56 (21.5%) were positive by Xpert® GBS PCR, including 50 where IAP was initiated before vaginal sampling. Overall, among the 565 women with GBS antenatal positive culture, only 335 (59.3%) were still positive at delivery whatever the technique used, resulting in unnecessary IAP for 40% of them. This large cohort study comparing intrapartum to antepartum GBS detection provides evidence that (i) Xpert® GBS PCR might be a valuable solution for intrapartum GBS detection compared to culture-based strategies and (ii) laboratory training of non-specialized staff is mandatory to reach the performances required for point-of-care tests.

Clinical and microbiological features associated with group B Streptococcus bone and joint infections, France 2004-2014.

This study describes the clinical and microbiological features associated with group B Streptococcus (GBS) bone and joint infections (BJIs). It was a retrospective analysis of adult cases of GBS BJIs reported to the French National Reference Center for Streptococci from January 2004 to December 2014. Clinical data and GBS molecular characteristics are reported. Strains were collected from 163 patients. The most frequent comorbidities were: solid organ cancer (n = 21, 21%) and diabetes mellitus (n = 20, 20%). The main infection sites were knee (47/155 = 30%) and hip (43/155 = 27%), and occurred on orthopedic devices in 71/148 cases (48%). CPS III (n = 47, 29%), Ia (n = 26, 16%) and V (n = 40, 25%) were predominant. Resistance to erythromycin, clindamycin and tetracycline was detected in 55/163 (34%), 35/163 (21%) and 132/163 (81%) strains, respectively. The most frequent sequence types were ST-1 (n = 21, 25%), ST-17 (n = 17, 20%) and ST-23 (n = 11, 13%). The rate of resistance to erythromycin was 0% for ST-17 strains, 52% (n = 11) for ST-1 and 44% (n = 7) for ST-23 (p < 0.001). GBS bone and joint infections predominantly occur in patients aged >50 years and/or with comorbidities such as cancer and diabetes mellitus. CPS type distribution and MLST are very similar to that of other adult GBS invasive infections.

Highly virulent M1 Streptococcus pyogenes isolates resistant to clindamycin.

CONTEXT: Emm1-type group A Streptococcus (GAS), or Streptococcus pyogenes, is mostly responsible for invasive infections such as necrotizing fasciitis (NF) and streptococcal toxic shock syndrome (STSS). The recommended treatment of severe invasive GAS infections is a combination of clindamycin and penicillin. Until 2012, almost all emm1 isolates were susceptible to clindamycin. OBJECTIVES: We aimed to identify the phenotypic and genotypic characteristics of emm1 GAS clone resistant to clindamycin. METHODS: GAS strains were characterized by emm sequence typing, detection of genes encoding pyrogenic exotoxins or superantigens. Cluster analysis was performed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Antibiotic susceptibility was assessed using disk diffusion and resistance genes were detected by PCR. RESULTS: A total of 1321 GAS invasive isolates were analyzed between January 2011 and December 2012. The overall number of invasive isolates resistant to clindamycin was 52 (3.9%); seven of them were emm1 isolates. All isolates had the same genomic markers: macrolide resistance due to the presence of the erm(B) gene, emm subtype 1.0, the same toxin or superantigen profile, PFGE pattern and sequence type. CONCLUSION: This is the first description of highly virulent GAS emm1 isolates resistant to clindamycin in France. This article strengthens the need for monitoring the epidemiology of invasive GAS strains as they could lead to changes in treatment guidelines.

[Epidemiology of Streptococcus pyogenes invasive diseases in France (2007-2011)]. / Épidémiologie des infections invasives à Streptococcus pyogenes (France 2007-2011).

Group A Streptococcus (GAS) is a human pathogen responsible for a wide range of clinical manifestations. An increase of GAS invasive infections has been described since the mid 1980s. To study the French epidemiology of invasive infections (i) we characterized all GAS invasive strains received at the French National Reference Center for streptococci (CNR-Strep) between 2007 and 2011; (ii) we analyzed the epidemiological data on the corresponding strains. For each strain, emm genotype, superantigen genes and antibiotics susceptibility were determined. Among the 2 603 non redundant invasive GAS strains, 65.1 % (n=1 695) were isolated from blood culture. A streptococcal toxic shock syndrome (STSS) was described in 16.4 % (n=428) of cases, mostly associated with necrotizing fasciitis (NF), pleuropulmonary or osteoarticular infections (p ≤0.001). The case fatality rate was 10.6 %. A total of 102 different emm genotypes were identified. Three emm genotypes predominated, reaching nearly 60 % of the strains: emm 1 (26.7 %), emm 28 (16.4 %), and emm 89 (12.8 %). The proportion of each emm genotype varied according to the year and the age of patients. Among those < 15 years old, the three main genotypes were emm 1 (36.8 %), emm 12 (12.9 %) and emm 4 (9.5 %). The distribution of superantigen genes (SpeA, SpeC and Ssa) was restricted to several emm genotypes. Between 2007 and 2011, the rate of macrolides resistant GAS strains decreased from 7.8 to 5.5 %. emm 1 strains are still the most common especially in most severe clinical manifestations including STSS and NF.

Identification of group A streptococcal emm types commonly associated with invasive infections and antimicrobial resistance by the use of multiplex PCR and high-resolution melting analysis.

M/emm typing, based either on serotyping of the M protein or on sequencing of the emm gene, is a major tool for epidemiological studies of group A streptococci (GAS). In order to simplify M/emm typing, we designed two multiplex polymerase chain reaction (PCR) formats capable of identifying the most frequent GAS M/emm types involved in invasive infections and antimicrobial resistance. A heptaplex PCR procedure was first developed in a conventional format coupled with gel electrophoresis to identify emm types 1, 3, 4, 6, 12, 28, and 89, based on the size of the amplification products. The other method, designed to identify the same seven emm types, together with emm11, was based on a real-time PCR format coupled with high-resolution melting (HRM) analysis, allowing the rapid typing of large strain collections.

Invasive group A streptococcal infections in adults, France (2006-2010).

Severe invasive group A streptococcal diseases have re-emerged during the past 10-20 years. In order to provide a better insight into the current epidemiological situation in France, we analysed the questionnaires regarding all invasive strains received at the National Reference Center for Streptococci (CNR-Strep) between 2006 and 2010 from patients aged ≥ 18 and characterized them by emm typing, spe gene detection and antibiotic resistance. Among the 1542 invasive GAS strains studied, 78% (n=1206) were from blood cultures, and a streptococcal toxic shock syndrome (STSS) was described in 22% (n=340) of cases, mainly associated with necrotizing fasciitis (NF) and pleuro-pulmonary infections (p<0.001). The in-hospital fatality rate was 15%. A total of 83 different emm types were recovered but the three predominant emm types, representing almost 60% of the isolates, were emm1 (24%), emm28 (17%) and emm89 (15%). The preponderance of each emm type varied according to the year, with a significant constant increase of emm28 strains, whereas emm1 strains, representing approximately 32% of GAS invasive isolates in 2007 and 2008, dropped to <15% in 2010 (p<0.001). The distribution of phage-associated superantigen genes (speA, speC and ssa) was linked to certain emm types. Between 2006 and 2010, the percentage that was macrolide-resistant decreased from 11% to 5%, confirming the trend observed in 2007. Fortunately, emm1 strains associated with the most life-threatening clinical manifestations remain susceptible to all anti-streptococcal antibiotics.

[Streptococcus pyogenes or group A streptococcal infections in child: French national reference center data]. / Infections à Streptococcus pyogenes ou streptocoque du groupe A chez l'enfant : données du Centre national de référence (CNR).

Since the 1980s, infections due to Streptococcus pyogenes or group A streptococci (GAS) were marked by the increase in invasive infections and the emergence of clones which were resistant to macrolides. Those challenges led the French national reference center for streptococci to enhance the epidemiological survey and the characterization of GAS strains, in collaboration with the National Institute for Public Health Surveillance. Active surveillance is of major importance for implementation of therapeutic and prophylactic guidelines and for evaluation of future streptococcal vaccines.

Reduced susceptibility to amoxicillin of oral streptococci following amoxicillin exposure.

As antibiotic pressure often triggers bacterial resistance, the use of short-duration therapies is increasingly recommended. The objective of the present study was to evaluate both the clinical efficiency and the impact on oral streptococci of a 3 day versus a 7 day amoxicillin therapy for odontogenic infection requiring tooth extraction. On day 0, patients were randomly assigned to a 3 day or 7 day amoxicillin treatment. The tooth was extracted on day 2 and the post-operative follow-up was carried out on day 9. Oral flora was collected on days 0, 9 and 30, and the susceptibility of the streptococci to amoxicillin was determined. The results showed that treatment with amoxicillin for 3 or 7 days had a similar clinical efficiency, and also induced similar selection of oral streptococci with reduced susceptibility to amoxicillin, suggesting that the selection of strains with reduced susceptibility to amoxicillin is a rapid phenomenon, appearing even with short-duration therapies.

[Epidemiology of candidemia: results of a one month French hospitals-based surveillance study in 2004]. / Epidémiologie des fongémies dans les hôpitaux français non universitaires en 2004: enquête multicentrique ColBVH.

INTRODUCTION: The aim of our study was to determinate the frequency of candidemia, the species encountered and their susceptibility to antifungal agents in French hospitals in 2004. METHODS: A prospective survey of septicaemia, including candidaemia was conducted among 193 non teaching French hospitals during October 2004. All bloodstream infections were reported and the bloodstream isolates sent to two coordinating centers. Species identification and susceptibility were performed by biologists as usual, and further confirmed by use of alternative methods, including Minimal Inhibitory Concentration (MIC) determination. RESULTS: The survey was effective in 93 hospitals, where 2013 bloodstream infections were noticed, including 46 candidaemia (2.3%). Candida sp. Is the 7th pathogen responsible for bloodstream infection, without concern of the origin of the infection. Candidaemia was hospital acquired in 80.4% of cases (N=37/46). Candidaemia represents 0.7% (N=9/1211) of community-acquired bloodstream infections but 4.5% (N=37/802) of nosocomial cases, placing Candida sp. at the 5th row of frequency in this last group. No mistakes were noticed during identification, but two strains were not named. After confirmation of identification, species are distributed as follows: 23 C.albicans (50%), 13 C.glabrata (28.3%), 5 C.tropicalis (10.9%), 3 C.parapsilosis (6.5%), 1 C.krusei (2.2%), and 1 C.kefyr (2.2%). The overall susceptibility is 97.7% for amphotericin B, 93.2% for 5-fluorocytosin, 88.6% for fluconazole, 70.5% for itraconazole, 95.5% for voriconzole and 100% of strains had very low MIC for caspofungin. Concerning the two main species isolated, 95.5% of C.albicans strains remain susceptible to fluconazole, but only 69% of C.glabrata strains. Two strains, 1 C.albicans and 1 C.glabrata exhibit cross resistance to azoles. The majority of amphotericin, fluconazole, and itraconazole decreased susceptibility strains are found into C.glabrata strains, but susceptibility to 5-fluorocytosin and very low MCI to caspofungin remained in this species. CONCLUSION: Our survey allowed us to get data from French non-teaching hospitals in 2004 about frequency of candidaemia among septicaemia. Candida species distribution and in vitro susceptibility patterns of the strains isolated. Candidaemia is not a rare event, specially when septicaemia is nosocomially acquired. C.albicans is the main species isolated and remains highly in vitro susceptible to antifungals. One important feature is the frequency of C.glabrata in our survey. Considering its decreased susceptibility to azoles, this finding confirms the need for rapid identification of yeast isolated from bloodstream samples, and antifungal susceptibility testing each time it is available.