Population pharmacokinetics and pharmacodynamics of imipenem in neutropenic adult patients.

OBJECTIVE: Imipenem is recommended in patients with chemotherapy-induced febrile neutropenia. Although alterations of antibiotic pharmacokinetic parameters have been reported in such patients, little data is available on imipenem. METHODS: Prospective, single-center, non-interventional pharmacokinetic cohort study in adults with chemotherapy-induced febrile neutropenia. Critically ill patients were excluded. Imipenem was administered as a 30-min infusion of 1000 mg/8h. Total imipenem plasma concentrations were assayed by high-performance liquid chromatography during neutropenia and just after neutrophil recovery. We estimated population pharmacokinetic parameters of imipenem by non-linear mixed-effect modelling using the SAEM algorithm. RESULTS: Sixteen patients were included in the study, including nine women (56.3%), median age 37 years (range, 18.3; 78.3). Eight patients had an hematological malignancy (50.0%) and seven had a solid tumor (43.8%). Imipenem pharmacokinetics were best described by a one-compartment model with first-order elimination. Mean values for imipenem were: clearance 14.3L/h and 10.9L/h and volume of distribution 20.7L and 14.5 L during neutropenia and after recovery, respectively. Imipenem plasma area under the curve at steady state was reduced by 23% during neutropenia. However, all patients achieved a pharmacodynamic target of %fT>MIC ≥ 40% with a regimen of 1000 mg/8 h or 500 mg/6 h, for MICs up to 2 mg/L. The pharmacodynamics profile for a target of %fT > MIC = 100% was however less favorable with 500 mg/6 h or 1000 mg/8 h either during or after neutropenia. CONCLUSION: Pharmacokinetic/pharmacodynamic goals for imipenem were similar in patients during and after neutropenia, despite reduced plasma exposure.

Mycoplasma genitalium screening in a specialized French unit: A retrospective study.

OBJECTIVE: Mycoplasma genitalium (MG) infection accounts for 10-35% of non-gonococcal non-chlamydial (NGNC) urethritis. However, given that most people infected with MG do not develop symptoms and that antimicrobial resistance is increasing worldwide, there is no evidence of any benefits of screening asymptomatic individuals. We conducted this study to describe MG screening practices and outcomes at a French Sexually Transmitted Infections (STI) center in which MG testing was performed selectively and multiplex assays were not carried out [i.e., simultaneous screening for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and MG]. METHODS: A retrospective, observational, single-center study was conducted at the STI unit of Saint-Louis Hospital in Paris. The records of all patients undergoing MG testing from January 1st, 2017, to December 31st, 2018, were reviewed. The primary aim of the study was to describe and evaluate the proportion of MG-positive (MG+) patients among those tested. Secondary objectives were determination of the prevalence of MG+ status among symptomatic patients, risk factors associated with MG infection, and therapeutic modalities and efficacy. RESULTS: Two hundred and forty-nine patients underwent MG testing, 28 (11%) of whom were positive (MG+). The prevalence of MG+ status among symptomatic NGNC patients was 12%. HIV-positive (HIV+) status was significantly associated with MG+ status in univariate and multivariate analyses (Odds Ratio=7.3, 95% Confidence Interval 1.3-41.7; P=0.02). Twenty-three patients (85%) received antibiotics. Eighteen (67%) received azithromycin for 5 days, but 7 had clinical resistance. No quinolone resistance was reported. CONCLUSION: Despite unavailability of multiplex testing at our facility, which led to targeted-only screening for MG, its relatively high local prevalence is in keeping with what is generally observed at similar facilities across the world, where use of multiplex tests enables systematic screening for MG alongside NG and CT. This reinforces the current recommendations in Europe, France and the US against systematic MG testing or treatment in asymptomatic patients.

Inoculum effect of Enterobacterales co-expressing OXA-48 and CTX-M on the susceptibility to ceftazidime/avibactam and meropenem.

BACKGROUND: The treatment of infections caused by OXA-48/CTX-M-coproducing Enterobacterales may be based on new beta-lactam/beta-lactamase inhibitors, such as ceftazidime/avibactam (CZA), or on high dose of meropenem (MER). However, bacterial density at the infection site may vary widely, and the inoculum effect of such antimicrobial strategies has never been specifically investigated. To determine if CZA or MER susceptibilities are impacted by high inocula of Enterobacterales co-expressing both enzymes: OXA-48 like and CTX-M. METHODS: Determination of an inoculum effect was performed with a standard inoculum of 108 CFU/mL (0.5 McFarland) as recommended by EUCAST guidelines and compared to a twofold increase as well as a tenfold increase (1 McFarland and 5 McFarland respectively). RESULTS: Thirty-nine isolates of ceftazidime-resistant Enterobacterales were included of which 27 (70%) co-expressed OXA-48 + CTX-M-15, 6 (15%) OXA-48 + CTX-M-14, and 6 (15%) OXA-181 + CTX-M-15. The susceptibility to the CZA combination was preserved whatever the inoculum used. Regarding MER, 24 (61.5%) of the isolates were susceptible to MER with the standard inoculum, 19 (48.7%) with a twofold increase, and only 15 (38.5%) with a tenfold increase. CONCLUSION: We showed that in vitro inoculum effect was observed with meropenem but not with CZA for OXA-48- combined with CTX-M-producing Enterobacterales.

Prevalence and risk factors for gonococcal infection in Reunion Island.

OBJECTIVE: To determine the prevalence and risk factors for gonococcal infection, and the resistance profile of Neisseria gonorrhoeae (NG) in Reunion Island. PATIENTS AND METHODS: All patients who visited the four sexually transmitted infection (STI) clinics of Reunion Island between January 2017 and December 2018 were screened by multiplex polymerase chain reaction. Data on patient characteristics were collected using a self-administered questionnaire (reason for screening, marital status, risk-taking behaviors, place of birth, employment status, type of health care coverage, sexual orientation, number of sexual partners, occurrence of extra-marital relationships, history of STIs, and symptomatology. Precarity was defined as being unemployed and/or receiving universal health insurance). RESULTS: The prevalence of NG (n=4289) in the screened population was 2.8% (95% CI [2.3-3.3]). Minors were especially at-risk (4.4% (95% CI [2.6-7])) and especially girls (5.6% (95% CI [3.2-8.9])). The prevalence observed in the homosexual population was 4.0% [2.6-5.9]. Gonococcal infection was asymptomatic in 56 (69%) patients. For all infection sites, the main risk factors were male minors (P=0.019), individuals living in conditions of precarity (P=0.023), individuals co-infected with chlamydia (P<0.001) or syphilis (P<0.001), and individuals of foreign origin (P=0.006). No NG strain was resistant to ceftriaxone. Strains were resistant to penicillin G, ciprofloxacin, and azithromycin in 22% (20/91), 38% (35/91), and 1% (1/91) of cases, respectively. CONCLUSION: The prevalence of NG in patients visiting STI clinics in Reunion Island is particularly high among minors. Prevention programs targeting this population should be reinforced and screening should be facilitated in school settings.

Utility of anaerobic bottles for the diagnosis of bloodstream infections.

BACKGROUND: Obligate anaerobes usually account for less than 10% of bacteria recovered from blood cultures (BC). The relevance of routine use of the anaerobic bottle is under debate. The aim of this study was to evaluate the utility of anaerobic bottles for the diagnosis of bloodstream infections (BSI). METHODS: We conducted a 6-month, retrospective, monocentric study in a tertiary hospital. All positive BC were grouped into a single episode of bacteremia when drawn within 7 consecutive days. Bacteremia were classified into contaminants and BSI. Charts of patients with BSI due to obligate anaerobes were studied. RESULTS: A total of 19,739 blood cultures were collected, 2341 of which (11.9%) were positive. Anaerobic bottles were positive in 1528 (65.3%) of all positive BC but were positive alone (aerobic bottles negative) in 369 (15.8%). Overall 1081 episodes of bacteremia were identified, of which 209 (19.3%) had positive anaerobic bottles alone. The majority 126/209 (60.3%) were contaminants and 83 (39.7%) were BSI. BSI due to facultative anaerobes, obligate aerobes and obligate anaerobes were identified in 67 (80.7%), 3 (3.6%) and 13 (15.7%) of these 83 episodes, respectively. BSI due to obligate anaerobic bacteria were reported in 9 patients with gastro-intestinal disease, in 3 with febrile neutropenia and in 1 burned patient. CONCLUSIONS: Anaerobic bottles contributed to the diagnosis of a significant number of episodes of bacteremia. Isolated bacteria were mostly contaminants and non-obligate anaerobic pathogens. Rare BSI due to obligate anaerobes were reported mainly in patients with gastro-intestinal disorders and during febrile neutropenia.

Association of Mycoplasma Hominis and head and neck cancer with unknown primary.

INTRODUCTION: Beside HPV infection, there is currently no evidence of association between head and neck squamous cell carcinomas and microbial infections. We report the case of a cervical squamous cell carcinoma by Mycoplasma hominis. CASE SUMMARY: A 20-year-old woman, consulted for a swelling on the left cervical side. Clinical examination found a large fixed mass. Biological tests found no evidence of infection. Biopsies of the cervical lesion diagnosed an HPV negative squamous cell carcinoma. Microbiological tests of 16sRNA identification showed the presence of Mycoplasma hominis in the 3 specimens. The patient was treated by induction chemotherapy associated to antibiotherapy, followed by chemo-radiotherapy. DISCUSSION: The present case suggests that oropharyngeal infection by Mycoplasma hominis might be more frequent than expected, that 16sRNA is an efficient technique to isolate this pathogen and finally that further studies are required to document its potential oncogenic role in head and neck squamous cell carcinomas.

Determination of Escherichia coli phylogroups in elderly patients with urinary tract infection or asymptomatic bacteriuria.

OBJECTIVES: Distinguishing between urinary tract infection (UTI) and asymptomatic bacteriuria (ABU) is difficult in the geriatric population since specific symptoms are often lacking. Escherichia coli is the most frequent UTI pathogen in this population but also a common urine colonizer. We hypothesized that detecting E. coli phylogroups B2 or D, which were previously associated with virulent strains responsible for extra-intestinal infections outside elderly patients, could help in distinguishing UTI from ABU. METHODS: Consecutive cases of E. coli bacteriuria diagnosed in hospitalized patients >75 years old during 3 months were investigated for E. coli phylogroups. Multiplex PCR was used to search for several virulence genes as previously described. Characteristics of UTI and ABU cases, assessed retrospectively according to definitions and geriatric expertise, were compared. RESULTS: Out of 233 bacteriuria cases, 60 were assessed to be UTI and 163 to be ABU, with 10 cases unclassified. E. coli strains belonging to the phylogroups B2 and D were significantly more frequent in UTI (48/60, 80%) than in ABU (101/163, 62%) by univariate and multivariate analyses (OR 3.05, 1.44-6.86, p 0.005). Out of all the host and bacterial characteristics studied, falls (p 0.032), comorbidities (p 0.041), and altered autonomy evaluated by a low activity of daily living score (p 0.027) were also associated with UTI using univariate and multivariate analysis. CONCLUSIONS: Determination of the E. coli phylogroup, in addition to some host characteristics, can help to distinguish UTI from ABU in elderly patients with bacteriuria. If this hypothesis is confirmed by prospective studies, then inappropriate use of antibiotics may be reduced in ABU cases.

Molecular epidemiology of penicillinase-producing Neisseria gonorrhoeae isolates in France.

OBJECTIVES: Characterizing the molecular epidemiology of antibiotic resistance is crucial for a better understanding of the evolution and spread of resistance in Neisseria gonorrhoeae. Here, we examine the molecular epidemiology of penicillinase-producing N. gonorrhoeae (PPNG) isolates in France. METHODS: We investigated 176 PPNG isolates collected between 2010 and 2012 by the National Reference Centre in France. Genotyping was performed using the NG-MAST technique, blaTEM genes were Sanger-sequenced, and plasmids were characterized by PCR-typing. RESULTS: We revealed the existence of four major clusters representing about one-third of PPNG circulating in France. These clusters were related to ST1479 (18/176, 10.2%), to ST1582 (15/176, 8.5%), to ST8922 (10/176, 5.6%), and to ST1285 (9/176, 5.1%). Wild-type TEM-1 was identified in 151 (151/176, 85.8%) PPNG isolates, and TEM-1 variants were mostly represented by the M182T mutation (14/176, 8%), followed by P14S/L (8/176, 4.5%), G228S (2/176, 1.1%), and Q269K (1/176, 0.6%). The blaTEM genes were carried by African (157/176, 89.2%), Asian (13/176, 7.4%), and Toronto/Rio (6/176, 3.4%) plasmids. The M182T variants were found in various genetic backgrounds, whereas the P14S variants were disseminated clonally. The G228S and Q269K variants belong to one of the four major clusters of PPNG, which suggests a recent de novo emergence of these mutations. CONCLUSIONS: Our results show that approximately one-third of the penicillinase-producing N. gonorrhoeae isolates in France belong to one of four major clusters and that the spread of the different TEM variants is associated with distinct patterns of molecular epidemiology.

Actinobaculum schaalii, a new cause of knee prosthetic joint infection in elderly.

Actinobaculum schaalii is an emerging pathogen particularly involved in urinary tract infection of elderly people and/or patient with urological risk factors of urinary tract infection. This microorganism is a difficult-to-diagnose pathogen and is rarely involved in systemic or deep infections. Here, we report the first case of prosthetic joint infection due to A. schaalii in an 84-year-old man with a benign prostatic hyperplasia associated with chronic retention of urine. This case underlines the importance to optimize the diagnosis of emerging uropathogens as A. schaalii, to prevent systemic infections, particularly in patients with orthopaedic implants.

Incidence of gonococcal and chlamydial infections and coverage of two laboratory surveillance networks, France, 2012.

Surveillance of sexually transmitted diseases in France is based on voluntary networks of laboratories and clinicians. Despite the importance of incidence data in improving knowledge about the national context and in international comparisons, such data were not previously available. During nationwide quality control of laboratories, mandatory for all laboratories, we conducted a survey in June 2013 to estimate the incidence rates of gonococcal and chlamydial infections for 2012 and to estimate the proportion of diagnoses performed (coverage) by the country's two laboratory-based sentinel networks for these diseases. Estimated incidence rates for 2012 were 39 per 100,000 persons aged 15 to 59 years for gonorrhoea and 257 per 100,000 persons aged 15 to 49 years for chlamydia. These rates were consistent with the average levels for a group of other Western countries. However, different estimates between countries may reflect disparate sources of surveillance data and diverse screening strategies. Better comparability between countries requires harmonising data sources and the presentation of results. Estimated coverage rates of the gonococcal and chlamydial infection surveillance networks in France in 2012 were 23% and 18%, respectively, with substantial regional variations. These variations justify improving the representativeness of these networks by adding laboratories in insufficiently covered areas.

High medical impact of implementing the new polymeric bead-based BacT/ALERT® FAPlus and FNPlus blood culture bottles in standard care.

Blood culture (BC) efficiency is critical for the diagnosis of bloodstream infection (BSI). We evaluated the impact on standard care of implementing the new BacT/ALERT® FAPlus and FNPlus BC bottles containing antibiotic-binding polymeric beads. We measured positivity rates and time to detection (TTD) during the first 10 months of implementation (PF) and during the previous 10-month period (PS) during which we were using standard aerobic (SA) or standard anaerobic (SN) BC bottles. For each period, the same number of consecutive patients (n = 3,918) was included. Per patient, a median of 1 BC set (1 aerobic and 1 anaerobic bottles) has been sampled. A higher positivity rate was measured during PF than PS when counting per BC bottle (7.0 % vs 5.8 % with 1,456 and 1,237 positive bottles respectively, P < 0.0001) and per BC set (9.6 % vs 7.8 % with 995 and 832 positive BC sets respectively, P < 0.0001). In PF, an increased number of cases due to staphylococci (P < 0.0001) and to Gram-negative bacilli (P < 0.005) was observed, whereas the contamination rate was similar during the two periods (2.4 % of BC sets in PF and 2.3 % in PS). Although antibiotic consumption and medical activity were similar during the two periods, BSI case detection increased from 2.2 to 2.6 per 1,000 hospital-days, especially in intensive care units (ICU; 35.1 to 55.7). Mean TTD for pathogenic microorganisms was significantly shorter in PF than in PS (15.5 h vs 18.0 h, P < 0.01). In conclusion, the use of the new FAPlus/FNPlus BC bottles improved the diagnosis of bacteremia in our hospital, especially in ICU patients.

Assessment of coinfection of sexually transmitted pathogen microbes by use of the anyplex II STI-7 molecular kit.

Anyplex STI-7 is a new molecular kit that detects seven sexually transmitted pathogens. Among 202 subjects screened for genital infection, 143 (70.4%) were diagnosed with at least one pathogen, in concordance with reference methods. In addition, the Anyplex STI-7 demonstrated coinfections, such as that with Ureaplasma parvum and Chlamydia trachomatis, in young women.

High-level azithromycin-resistant Neisseria gonorrhoeae clinical isolate in France, March 2014.

We report the first case in France of a high-level azithromycin-resistant Neisseria gonorrhoeae (minimum inhibitory concentration (MIC) = 96 mg/L) assigned to MLST7363 (NG-MAST ST6360), also resistant to ciprofloxacin and tetracycline but susceptible to ceftriaxone. The patient was a 51 year-old heterosexual man who returned following 1g azithromycin monotherapy. Mechanisms of azithromycin resistance were a C2599T mutation in the four copies of the rrl gene and a novel mutation in the promoter of the mtrR gene.

Prosthetic knee arthritis due to Granulicatella adiacens after dental treatment.

We report prosthetic knee arthritis in a 55-year-old diabetic man due to Granulicatella adiacens, a micro-organism present in the oral flora, usually described in endocarditis but rarely in prosthesis joint infection. This patient had undergone a dental extraction without antibiotic prophylaxis one month before, and an aseptic loosening of the prosthesis had been diagnosed previously. If antimicrobial prophylaxis against infective endocarditis for dental procedures is well established, such an approach is still controversial for joint prosthesis and should be considered in some conditions.

Postoperative spondylodiscitis due to Kytococcus schroeteri in a diabetic woman.

Kytococcus schroeteri, a Gram-positive coccus, is usually regarded as part of the human skin flora. It has been described in prosthetic valve endocarditis but never as being involved in osteoarticular infections. We report here the first case of a spondylodiscitis due to K. schroeteri identified by 16S rRNA gene sequencing.