Evaluation of ceftolozane-tazobactam susceptibility on a French nationwide collection of Enterobacterales.

OBJECTIVES: Ceftolozane-tazobactam (C/T) proved its efficacy for the treatment of infections caused by non-carbapenemase producing Pseudomonas aeruginosa and Enterobacterales. Here, we aimed to provide susceptibility data on a large series of Enterobacterales since the revision of EUCAST categorization breakpoints in 2020. METHODS: First, C/T susceptibility was determined on characterized Enterobacterales resistant to third generation cephalosporins (3GCs) (extended spectrum ß-lactamase [ESBL] production or different levels of AmpC overexpression) (n = 213) and carbapenem-resistant Enterobacterales (CRE) (n = 259), including 170 carbapenemase producers (CPE). Then, 1632 consecutive clinical Enterobacterales responsible for infection were prospectively collected in 23 French hospitals. C/T susceptibility was determined by E-test® (biomérieux) and broth microdilution (BMD) (Sensititre™, Thermo Scientific) to perform method comparison. RESULTS: Within the collection isolates, 88% of 3GC resistant strains were susceptible to C/T, with important variation depending on the resistance mechanism: 93% vs. 13% susceptibility for CTX-M and SHV-ESBL producers, respectively. Only 20% of the CRE were susceptible to C/T. Among CPE, 80% of OXA-48-like producers were susceptible to C/T, whereas all metallo-ß-lactamase producers were resistant. The prospective study revealed that 95.6% of clinical isolates were susceptible to C/T. Method comparison performed on these 1632 clinical isolates demonstrated 99% of categorization agreement between MIC to C/T determined by E-test® in comparison with the BMD (reference) and only 74% of essential agreement. CONCLUSION: Overall, C/T showed good activity against wild-type Enterobacterales, AmpC producers, and ESBL-producing Escherichia coli but is less active against ESBL-producing Klebsiella pneumoniae, and CRE. E-test® led to an underestimation of the MICs in comparison to the BMD reference.

Investigation of a COVID-19 outbreak on the Charles de Gaulle aircraft carrier, March to April 2020: a retrospective cohort study.

BackgroundSARS-CoV-2 emergence was a threat for armed forces. A COVID-19 outbreak occurred on the French aircraft carrier Charles de Gaulle from mid-March to mid-April 2020.AimTo understand how the virus was introduced, circulated then stopped circulation, risk factors for infection and severity, and effectiveness of preventive measures.MethodsWe considered the entire crew as a cohort and collected personal, clinical, biological, and epidemiological data. We performed viral genome sequencing and searched for SARS-CoV-2 in the environment.ResultsThe attack rate was 65% (1,148/1,767); 1,568 (89%) were included. The male:female ratio was 6.9, and median age was 29 years (IQR: 24-36). We examined four clinical profiles: asymptomatic (13.0%), non-specific symptomatic (8.1%), specific symptomatic (76.3%), and severe (i.e. requiring oxygen therapy, 2.6%). Active smoking was not associated with severe COVID-19; age and obesity were risk factors. The instantaneous reproduction rate (Rt) and viral sequencing suggested several introductions of the virus with 4 of 5 introduced strains from within France, with an acceleration of Rt when lifting preventive measures. Physical distancing prevented infection (adjusted OR: 0.55; 95% CI: 0.40-0.76). Transmission may have stopped when the proportion of infected personnel was large enough to prevent circulation (65%; 95% CI: 62-68).ConclusionNon-specific clinical pictures of COVID-19 delayed detection of the outbreak. The lack of an isolation ward made it difficult to manage transmission; the outbreak spread until a protective threshold was reached. Physical distancing was effective when applied. Early surveillance with adapted prevention measures should prevent such an outbreak.

Antimicrobial Resistance in Enterobacterales Recovered from Urinary Tract Infections in France.

In the context of increasing antimicrobial resistance in Enterobacterales, the management of these UTIs has become challenging. We retrospectively assess the prevalence of antimicrobial resistance in Enterobacterales isolates recovered from urinary tract samples in France, between 1 September 2017, to 31 August 2018. Twenty-six French clinical laboratories provided the susceptibility of 134,162 Enterobacterales isolates to 17 antimicrobials. The most frequent species were E. coli (72.0%), Klebsiella pneumoniae (9.7%), Proteus mirabilis (5.8%), and Enterobacter cloacae complex (2.9%). The overall rate of ESBL-producing Enterobacterales was 6.7%, and ranged from 1.0% in P. mirabilis to 19.5% in K. pneumoniae, and from 3.1% in outpatients to 13.6% in long-term care facilities. Overall, 4.1%, 9.3% and 10.5% of the isolates were resistant to cefoxitin, temocillin and pivmecillinam. Cotrimoxazole was the less active compound with 23.4% resistance. Conversely, 4.4%, 12.9%, and 14.3% of the strains were resistant to fosfomycin, nitrofurantoin, and ciprofloxacin. However, less than 1% of E. coli was resistant to fosfomycin and nitrofurantoin. We identified several trends in antibiotics resistances among Enterobacterales isolates recovered from the urinary tract samples in France. Carbapenem-sparing drugs, such as temocillin, mecillinam, fosfomycin, cefoxitin, and nitrofurantoin, remained highly active, including towards ESBL-E.

High Prevalence of OXA-23 Carbapenemase-Producing Proteus mirabilis among Amoxicillin-Clavulanate-Resistant Isolates in France.

In this multicentric study performed in 12 French hospitals, we reported that 26.9% (14/52) of the amoxicillin-clavulanate-resistant Proteus mirabilis isolates produced the OXA-23 carbapenemase. We found that an inhibition zone diameter of <11 mm around the amoxicillin-clavulanate disc was an accurate screening cutoff to detect these OXA-23 producers. We confirmed by whole-genome sequencing that these OXA-23-producers all belonged to the same lineage that has been demonstrated to disseminate OXA-23 or OXA-58 in P. mirabilis.

Prevalence of leukocyturia in a cohort of French asymptomatic aircrews.

OBJECTIVES: Sexually transmitted infections (STIs) can cause leukocyturia. We aimed to estimate the prevalence of leukocyturia in asymptomatic aircrews and the proportion of STIs in those presenting leukocyturia. METHODS: The LEUCO survey was a prospective cohort study conducted among aircrews between 14th October 2019 and 13th March 2020 at the Toulon aeromedical centre in France. All participants performed a dipstick urinalysis. Those positive for leukocyturia were offered STI screening by nucleic acid amplification test (NAAT) for Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium and Trichomonas vaginalis. RESULTS: Among the 2236 included asymptomatic participants (1912 men and 324 women), 127 (36 men and 91 women) were positive for leukocyturia. The prevalence of leukocyturia was 1.9% (1.3-2.6) in men and 28.1% (23.3-33.3) in women (p < 0.001). In men positive for leukocyturia, the NAAT positivity rate for C. trachomatis, N. gonorrhoeae, M. genitalium and T. vaginalis was 28.6% (3.7-71.0) in the age group 18-24, 20.0% (0.5-71.6) in the age group 25-34, and zero in the older age group (p 0.65). In women positive for leukocyturia it was 16.7% (4.7-37.4) in the age group 18-24, 18.2% (2.3-51.8) in the age group 25-34, and zero in the older age group (p 0.16). CONCLUSIONS: In asymptomatic individuals, leukocyturia is rare in men and more common in women. In asymptomatic adults under 35 years of age with leukocyturia, multiplex NAAT shows a high proportion of STIs and might be useful in improving STI detection.

Neutralizing antibody response to SARS-CoV-2 persists 9 months post symptom onset in mild and asymptomatic patients.

OBJECTIVE: A better understanding of the immune response against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is critical to predict its dynamics within the general population and its impact on the vaccination strategy. This study assessed the persistence of neutralizing antibody (Nab) activity and SARS-CoV-2 serology in serum samples of mild and asymptomatic patients 9 months post symptom onset (PSO) in a primary care context among immunocompetent adults. METHODS: A longitudinal cohort of crew members (CMs) exposed to coronavirus disease 2019 (COVID-19) during an outbreak of SARS-CoV-2 on the French aircraft carrier 'Charles de Gaulle' in April 2020 was created. CMs infected with COVID-19 and with positive serology at the end of quarantine were tested 9 months PSO. Samples were collected 18 and 280 days PSO. For each patient, both serology and serum viral neutralizing activity were performed. RESULTS: In total, 86 CMs were analysed. Samples were collected 18 and 280 days PSO. The seroconversion rates were 100% and 93% (82/86) at 18 and 280 days PSO, respectively, and 72.7% of patients exhibited persistent Nab activity at 9 months, regardless of disease severity. CONCLUSION: Nab activity persists for up to 9 months following asymptomatic/mild COVID-19 among young adults, regardless of serological results.

In Vitro Antimicrobial Susceptibility Profiles of Gram-Positive Anaerobic Cocci Responsible for Human Invasive Infections.

The aim of this multicentre study was to determine the in vitro susceptibility to anti-anaerobic antibiotics of Gram-positive anaerobic cocci (GPAC) isolates responsible for invasive infections in humans. A total of 133 GPAC isolates were collected in nine French hospitals from 2016 to 2020. All strains were identified to the species level (MALDI-TOF mass spectrometry, 16S rRNA sequencing). Minimum inhibitory concentrations (MICs) of amoxicillin, piperacillin, cefotaxime, imipenem, clindamycin, vancomycin, linezolid, moxifloxacin, rifampicin, and metronidazole were determined by the reference agar dilution method. Main erm-like genes were detected by PCR. The 133 GPAC isolates were identified as follows: 10 Anaerococcus spp., 49 Finegoldia magna, 33 Parvimonas micra, 30 Peptoniphilus spp., and 11 Peptostreptococcus anaerobius. All isolates were susceptible to imipenem, vancomycin (except 3 P. micra), linezolid and metronidazole. All isolates were susceptible to amoxicillin and piperacillin, except for P. anaerobius (54% and 45% susceptibility only, respectively). MICs of cefotaxime widely varied while activity of rifampicin, and moxifloxacin was also variable. Concerning clindamycin, 31 were categorized as resistant (22 erm(A) subclass erm(TR), 7 erm(B), 1 both genes and 1 negative for tested erm genes) with MICs from 8 to >32 mg/L. Although GPACs are usually susceptible to drugs commonly used for the treatment of anaerobic infections, antimicrobial susceptibility should be evaluated in vitro.

Performances, feasibility and acceptability of nasopharyngeal swab, saliva and oral-self sampling swab for the detection of severe acute respiratory syndrome coronavirus 2.

Molecular diagnosis on nasopharyngeal swabs (NPS) is the current standard for COVID-19 diagnosis, but saliva may be an alternative specimen to facilitate access to diagnosis. We compared analytic performances, feasibility and acceptability of NPS, saliva, and oral-self sampling swab for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A prospective, multicenter study was conducted in military hospitals in France among adult outpatients attending COVID-19 diagnosis centers or hospitalized patients. For each patient, all samples were obtained and analyzed simultaneously with RT-PCR or transcription-mediated amplification method. Clinical signs, feasibility, and acceptability for each type of sample were collected. A total of 1220 patients were included, corresponding to 1205 NPS and saliva and 771 OS. Compared to NPS, the sensitivity, specificity, and kappa coefficient for tests performed on saliva were 87.8% (95% CI 83.3-92.3), 97.1% (95% CI 96.1-98.1), and 0.84 (95% CI 0.80-0.88). Analytical performances were better in symptomatic patients. Ct values were significantly lower in NPS than saliva. For OS, sensitivity was estimated to be 61.1% (95% CI 52.7-69.4) and Kappa coefficient to be 0.69 (95% CI 0.62-0.76). OS was the technique preferred by the patients (44.3%) before saliva (42.4%) and NPS (13.4%). Instructions were perceived as simple by patients (> 90%) for saliva and OS. Finally, the painful nature was estimated to be 0.9 for OS, on a scale from 0 to 10, and to be 5.3 for NPS. Performances of OS are not sufficient. Saliva is an acceptable alternative to NPS for symptomatic patient but the process required additional steps to fluidize the sample.

Impact of Tobacco Smoking on the Risk of COVID-19: A Large Scale Retrospective Cohort Study.

INTRODUCTION: Preliminary reports indicated that smokers could be less susceptible to coronavirus SARS-CoV-2, which causes Covid-19. However, once infected an increased risk of severe disease is reported. We investigated the association between smoking and COVID-19 during an outbreak of the disease on a naval vessel. METHODS: We conducted a cross-sectional, observational study on the 1769 sailors of the same navy aircraft carrier at sea exposed at the same time to SARS-CoV2 to investigate the link between tobacco consumption and Covid-19. RESULTS: Among the 1688 crewmembers (87% men; median age = 28 [interquartile range 23-35]) included, 1279 (76%) developed Covid-19 (1038 [62%] reverse-transcriptase- polymerase chain reaction testing-positive and 241 [14%] with only clinical signs). One hundred and seven patients were hospitalized. The univariable analysis odds ratio (OR) for Covid-19 infection was 0.59 (95% confidence interval [CI], 0.45-0.78; p < .001) for current smokers versus former and nonsmokers; sex, body mass index or blood group had no significant impact. Crewmembers >50 years old had an increased risk of contracting Covid-19 (OR, 2.84 [95% CI, 1.30-7.5]; p = .01). Multivariable analysis retained the lower risk of current smokers becoming infected (OR, 0.64 [0.49-0.84]; p < .001) and age >50 years was significatively associated with Covid-19 (OR, 2.6 [1.17-6.9]; p = .03). CONCLUSIONS: Current smoking status was associated with a lower risk of developing Covid-19 but cannot be considered as efficient protection against infection. The mechanism of the lower susceptibility of smokers to SARS-CoV-2 requires further research. TRIAL REGISTRATION: IRB no.: 0011873-2020-09. IMPLICATIONS: (1) Recent epidemiologic data suggest a paradoxical link between smoking and COVID-19. (2) Among the 1688 crewmembers (with an attack rate of 76% and exposed at the same time in the same place to SARS-CoV2), we found a significantly lower risk for developing COVID-19 in current smokers (71%) versus former and nonsmokers (80%). This finding strongly supports the need for further research on nicotine physiological pathway and its impact on COVID-19 infection whilst emphasizing that tobacco smoking should not be considered as efficient protection against COVID-19.

Disseminated Mycobacterium chimaera Following Open-Heart Surgery, the Heater-Cooler Unit Worldwide Outbreak: Case Report and Minireview.

Invasive cardiovascular infections by Mycobacterium chimaera associated with open-heart surgery have been reported worldwide since 2013. Here, we report a case of a 61 year old man, without any other particular medical background, who underwent cardiac surgery for replacing part of the ascending aorta by a bio-prosthetic graft. Eighteen months later, the patient was painful at the lower back with fever. A pyogenic vertebral osteomyelitis due to M. chimaera associated to graft infection was diagnosed after 6 months of sub-acute infection. The patient presented a disseminated disease with cerebral lesions, chorioretinitis, and chronic renal failure. Despite adequate antimicrobial treatment and graft explantation, the patient died after 6 years. We reviewed the literature on M. chimaera infections associated with open-heart surgery. The worldwide outbreak has been explained by airborne bioaerosol generated by the 3T heater-cooler unit (HCU) used during cardiac by-pass surgical procedures. These infections are difficult to diagnose because of a long latency period (up to several years), with no specific symptoms and a highly specialized microbiological diagnosis. The treatment is based on antibiotics and surgery. These infections are also difficult to treat, since the mortality rate is high around 50%. Prevention is necessary by modifying the use of HCUs in operating rooms.

Acquisition of class C ß-lactamase PAC-1 by ST664 strains of Pseudomonas aeruginosa.

Four ST664 (serotype O:5) strains of Pseudomonas aeruginosa highly resistant to antibiotics including ceftolozane/tazobactam and ceftazidime/avibactam but susceptible to colistin, were found to harbor the rare class C ß-lactamase PAC-1 encoding gene on a chromosomally-located Tn1721-like transposon. Gene bla PAC-1 was associated with the 16S rRNA methylase determinant rmtF2, that confers pan-aminoglycoside resistance. These genotypically-related strains were isolated in repatriated patients from Mauricius and Afghanistan and close to a lineage reported in Nepal, Pakistan and India.

Influenza B false-positive results by rapid molecular tests Alere™ i Influenza A&B 2 in France.

The Alere-i™ Influenza A&B (Abbott), a nicking endonuclease amplification reaction test, has recently been improved in order to deliver results in a few minutes. Our field observation highlights two problems with this new version: improper interpretation of a test as valid despite improper reagent hydration and falsely influenza B positive results. We advise users of the new system to check reagent hydration prior to reporting a result and to systematically confirm positive influenza B results.

Occupational Exposures to Ebola Virus in Ebola Treatment Center, Conakry, Guinea.

We report 77 cases of occupational exposures for 57 healthcare workers at the Ebola Treatment Center in Conakry, Guinea, during the Ebola virus disease outbreak in 2014-2015. Despite the high incidence of 3.5 occupational exposures/healthcare worker/year, only 18% of workers were at high risk for transmission, and no infections occurred.

Decontamination of a field laboratory dedicated to Ebola virus-infected patients.

In 2015, the French Armed Forces deployed a biosafety level 3 (BSL3) field laboratory as a part of an Ebola treatment center in Guinea. When closing the center, laboratory decontamination operations were necessary. We present the decontamination protocols applied for the BSL3 field laboratory, making the entire module ready for a future use.