Emergence and rapid dissemination of highly resistant NDM-14-producing Klebsiella pneumoniae ST147, France, 2022.

BackgroundSince 2021, an emergence of New Delhi metallo-ß-lactamase (NDM)-14-producing Klebsiella pneumoniae has been identified in France. This variant with increased carbapenemase activity was not previously detected in Enterobacterales.AimWe investigated the rapid dissemination of NDM-14 producers among patients in hospitals in France.MethodsAll NDM-14-producing non-duplicate clinical isolates identified in France until June 2022 (n = 37) were analysed by whole genome sequencing. The phylogeny of NDM-14-producers among all K. pneumoniae sequence type (ST) 147 reported in France since 2014 (n = 431) was performed. Antimicrobial susceptibility testing, conjugation experiments, clonal relationship and molecular clock analysis were performed.ResultsThe 37 NDM-14 producers recovered in France until 2022 belonged to K. pneumoniae ST147. The dissemination of NDM-14-producing K. pneumoniae was linked to a single clone, likely imported from Morocco and responsible for several outbreaks in France. The gene bla NDM-14 was harboured on a 54 kilobase non-conjugative IncFIB plasmid that shared high homology with a known bla NDM-1-carrying plasmid. Using Bayesian analysis, we estimated that the NDM-14-producing K. pneumoniae ST147 clone appeared in 2020. The evolutionary rate of this clone was estimated to 5.61 single nucleotide polymorphisms per genome per year. The NDM-14 producers were highly resistant to all antimicrobials tested except to colistin, cefiderocol (minimum inhibitory concentration 2 mg/L) and the combination of aztreonam/avibactam.ConclusionHighly resistant NDM-14 producing K. pneumoniae can rapidly spread in healthcare settings. Surveillance and thorough investigations of hospital outbreaks are critical to evaluate and limit the dissemination of this clone.

Q Fever as a Cause of Community-Acquired Pneumonia in French Guiana.

In French Guiana, community-acquired pneumonia (CAP) represents over 90% of Coxiella burnetii acute infections. Between 2004 and 2007, we reported that C. burnetii was responsible for 24.4% of the 131 CAP hospitalized in Cayenne. The main objective of the present study was to determine whether the prevalence of Q fever pneumonia remained at such high levels. The secondary objectives were to identify new clinical characteristics and risk factors for C. burnetii pneumonia. A retrospective case-control study was conducted on patients admitted in Cayenne Hospital, between 2009 and 2012. All patients with CAP were included. The diagnosis of acute Q fever relied on titers of phase II IgG ≥ 200 and/or IgM ≥ 50 or seroconversion between two serum samples. Patients with Q fever were compared with patients with non-C. burnetii CAP in bivariate and multivariate analyses. During the 5-year study, 275 patients with CAP were included. The etiology of CAP was identified in 54% of the patients. C. burnetii represented 38.5% (106/275; 95% CI: 31.2-45.9%). In multivariate analysis, living in Cayenne area, being aged 30-60 years, C-reactive protein (CRP) > 185 mg/L, and leukocyte count < 10 G/L were independently associated with Q fever. The prevalence of Q fever among CAP increased to 38.5%. This is the highest prevalence ever reported in the world. This high prevalence justifies the systematic use of doxycycline in addition to antipneumococcal antibiotic regimens.

Impact of vaccination on the symptoms of hospitalised patients with SARS-CoV-2 Delta variant (B.1.617.1) infection.

OBJECTIVES: The diffusion of the SARS-CoV-2 Delta (B.1.617.2) variant and the waning of immune response after primary Covid-19 vaccination favoured the breakthrough SARS-CoV-2 infections in vaccinated subjects. To assess the impact of vaccination, we determined the severity of infection in hospitalised patients according to vaccine status. METHODS: We performed a retrospective observational study on patients hospitalised in 10 centres with a SARS-CoV-2 infection (Delta variant) from July to November 2021 by including all patients who had completed their primary vaccination at least 14 days before hospital admission and the same number of completely unvaccinated patients. We assessed the impact of vaccination and other risk factors through logistic regression. RESULTS: We included 955 patients (474 vaccinated and 481 unvaccinated). Vaccinated patients were significantly older (75.0 [63.25-84.0] vs. 55.0 [38.0-73.0]; p < 0.001), more frequently males (55.1% (261/474) vs. 46.4% (223/481); p = 0.009), and had more comorbidities (2.0 [1.0-3.0] vs. 1.0 [0.0-2.0]; p < 0.001). Vaccinated patients were less often admitted for Covid-19 (59.3% (281/474) vs. 75.1% (361/481); p < 0.001), had less extended lung lesions (≤25%: 64.3% (117/182) vs. 38.4% (88/229); p < 0.001), required oxygen less frequently (57.5% (229/398) vs. 73.0% (270/370); p < 0.001), at a lower flow (3.0 [0.0-8.7] vs. 6.0 [2.0-50.0] L/min, p < 0.001), and for a shorter duration (3 [0.0-8.0] vs. 6 [2.0-12.0] days, p < 0.001)., and required less frequently intensive care unit admission (16.2% (60/370) vs. 36.0% (133/369); p < 0.001) but had comparable mortality in bivariate analysis (16.7% (74/443) vs. 12.2% (53/433); p = 0.075). Multivariate logistic regression showed that vaccination significantly decreased the risk of death (0.38 [0.20-0.70](p = 0.002), ICU admission (0.31 [0.21-0.47](p < 0.001) and oxygen requirement (0.16 [0.10-0.26](p < 0.001), even among older patients or with comorbidities. CONCLUSIONS: Among patients hospitalised with a delta variant SARS-CoV-2 infection, vaccination was associated with less severe forms, even in the presence of comorbidities.

Influence of geographic origin on AIDS and serious non-AIDS morbidity/mortality during cART among heterosexual HIV-infected men and women in France.

BACKGROUND: The influence of geographic origin on the risk of severe illness and death on cART has not been explored in European countries. METHOD: We studied antiretroviral-naïve heterosexual HIV-1-infected individuals enrolled in the FHDH-ANRS CO4 cohort in France who started cART between 2006 and 2011. Individuals originating from France (French natives), sub-Saharan Africa (SSA) and non-French West-Indies (NFW) were studied until 2012. Crude and adjusted rate ratios (aRR) of severe morbid events/deaths (AIDS-related and non-AIDS-related) were calculated using Poisson regression models stratified by sex, comparing each group of migrants to French natives. RESULTS: Among 2334 eligible men, 1379 (59.1%) originated from France, 838 (35.9%) from SSA and 117 (5.0%) from NFW. SSA male migrants had a higher aRR for non-AIDS infections, particularly bacterial infections (aRR 1.56 (95% CI 1.07-2.29), p = 0.0477), than French natives. Among 2596 eligible women, 1347 (51.9%) originated from France, 1131 (43.6%) from SSA, and 118 (4.5%) from NFW. SSA and NFW female migrants had a higher aRR for non-AIDS infections, particularly non-bacterial infections (respectively, 2.04 (1.18-3.53) and 7.87 (2.54-24.4), p = 0.0010), than French natives. We observed no other significant differences related to geographic origin as concerns the aRRs for AIDS-related infections or malignancies, or for other non-AIDS events/deaths such as cardiovascular disease, neurological/psychiatric disorders, non-AIDS malignancies and iatrogenic disorders, in either gender. CONCLUSION: Heterosexual migrants from SSA or NFW living in France have a higher risk of non-AIDS-defining infections than their French native counterparts. Special efforts are needed to prevent infectious diseases among HIV-infected migrants.

Q fever epidemic in Cayenne, French Guiana, epidemiologically linked to three-toed sloth.

A Q fever epidemic occurred in 2013 in a small military residential area in Cayenne, French Guiana. A retrospective cohort study was conducted to identify Q fever risk factors. Confirmed acute Q fever case was defined as positive serology (IgM ≥ 50 and phase II IgG ≥ 200) and/or positive qPCR on serum or blood. In addition, wild mammals were captured at the study site and tested by serology and real-time PCR performed on blood, vaginal swabs and ticks. The attack rate was 20 percent (11/54). All the cases were symptomatic with fever >38.5 °C and community-acquired pneumonia for four cases. Log binomial multivariate models identified two independent risk factors associated with Q fever: to clean the house (RRa = 7.5 CI95% [1.03-55.3]) and to carry a three-toed sloth in arms (RRa = 2.6 CI95% [1.1-5.8]). Eighteen marsupial individuals were captured, all PCRs were negative but 17% (3/18) had a positive serology. Another study conducted after the epidemic found only one (1/4) three-tooth sloth (Bradypus tridactylus) with feces highly infectious for C. burnetii MST17. The same strain C. burnetii genotype 17 has been laboratory- confirmed in this mammal and in human cases. These results support the implication of three-toed-sloth in this epidemic. Human contamination mainly occurs through inhalation of infectious aerosols as suggested by high relative risk associated with house cleaning activities and pulmonary forms of the disease, and through direct contact with three- toed-sloth. Positive serological results among marsupials confirm wildlife exposure and suggest a more complex sylvatic transmission cycle among wild mammals.

Salmonella enterica serovar Panama meningitis in exclusive breastfeeding infants: Report of 4 cases, clinical features and therapeutic challenges.

RATIONALE: The pathway of Nontyphoid Salmonella meningitis, especially in exclusive breastfeeding infants, has not been well characterized. PATIENT CONCERNS: We analyzed data related to nontyphoid Salmonella meningitis in 4 infants. DIAGNOSES: No diarrhea was observed and the coproculture was negative for all patients. INTERVENTIONS: Early diagnosis and treatment with combination of third-generation cephalosporins plus quinolones for a minimum of 3 weeks is necessary to avoid severe sequelae and death. OUTCOMES: The first 3 patients had a good evolution, whereas the last patient had multiple brain abscesses and hydrocephalus requiring treatment with a ventriculoperitoneal shunt. LESSONS: The highlights of our study are that all infants were exclusively breastfed, no diarrhea observed and the negative coproculture for all the 4 patients, which is relatively rare for Salmonella infection.

Influence of geographic origin, sex, and HIV transmission group on the outcome of first-line combined antiretroviral therapy in France.

BACKGROUND: More data are needed on the influence of geographic origin, sex, and the HIV transmission group on biological and clinical outcomes after first-line combined antiretroviral therapy (cART) initiation. METHODS: We studied antiretroviral-naive HIV-1-infected adults enrolled in the French Hospital Database on HIV cohort in France and who started cART between 2006 and 2011. The censoring date of the study was 31 December 2012. According to geographic origin [French natives (FRA) or sub-Saharan Africa/non-French West Indies (SSA/NFW)], sex, and HIV transmission group, we assessed 2-year Kaplan-Meier probabilities and adjusted hazard ratios (aHRs) for plasma viral load undetectability and CD4 cell recovery, and 5-year cumulative incidences and aHRs for negative clinical outcomes (AIDS-defining event, serious non-AIDS events, or death). RESULTS: Of 9746 eligible individuals, 7297 (74.9%) were FRA and 2449 (25.1%) were sub-Saharan Africa/non-French West Indies migrants. More migrants (38.1%) than nonmigrants (27.5%) started cART with a CD4 cell count less than 200/µl (P < 0.0001). By comparison with FRA MSM, nonhomosexual men, whatever their geographic origin, had lower aHRs for viral undetectability; all patient groups, particularly migrants, had lower aHRs for CD4 cell recovery than FRA MSM; aHRs for negative clinical outcome (360 new AIDS-defining events, 1376 serious non-AIDS events, 38 deaths) were also higher in nonhomosexual men, regardless of geographic origin. Preexisting AIDS status, a lower CD4 cell count and older age at cART initiation had the biggest impact on changes between the crude and aHRs of clinical outcomes. CONCLUSION: Compared with FRA MSM, all migrants had a lower likelihood of CD4 cell recovery, and nonhomosexual men had a higher likelihood of negative virological and clinical outcomes.

Clinical epidemiology and resistance mechanisms of carbapenem-resistant Acinetobacter baumannii, French Guiana, 2008-2014.

This study investigated the clinical epidemiology and resistance mechanisms of Acinetobacter baumannii and characterised the clonal diversity of carbapenem-resistant A. baumannii (CRAB) during an ICU-associated outbreak at Cayenne Hospital, French Guiana. All non-duplicate A. baumannii isolates from 2008 to 2014 were tested for antibiotic susceptibility by disk diffusion. Multilocus sequence typing, pulsed-field gel electrophoresis (PFGE) and characterisation of carbapenemase-encoding genes were performed on CRAB. Of the 441 A. baumannii isolates, most were from males (54.0%) and were detected mainly from the ICU (30.8%) and medicine wards (21.8%). In the ICU, strains were mainly isolated from the respiratory tract (44.1%) and bloodstream (14.0%), whereas in medicine wards they mainly were from wound/drainage (36.5%) and bloodstream (25.0%). A. baumannii showed the greatest susceptibility to piperacillin/tazobactam (92.7%), imipenem (92.5%), colistin (95.6%) and amikacin (97.2%), being lower in the ICU and medicine wards compared with other wards. An outbreak of OXA-23-producing CRAB occurred in the 13-bed ICU in 2010. CRAB strains were more co-resistant to other antimicrobials compared with non-CRAB. Molecular genetics analysis revealed five sequence types [ST78, ST107 and ST642 and two new STs (ST830 and ST831)]. Analysis of PFGE profiles indicated cross-transmissions of CRAB within the ICU, between the ICU and one medicine ward during transfer of patients, and within that medicine ward. This study provides the first clinical and molecular data of A. baumannii from French Guiana and the Amazon basin. The ICU was the highest risk unit of this nosocomial outbreak of OXA-23-producing CRAB, which could subsequently disseminate within the hospital.

A predictive score for hypotension in patients with confirmed dengue fever in Cayenne Hospital, French Guiana.

Background: Identifying patients at risk of developing severe dengue is challenging. The objective of the present study was to determine the incidence of hypotension and its predictive factors during the Dengue 2 epidemic in 2013. Methods: In 2013, a longitudinal study was performed using data from all confirmed cases of dengue seen in Cayenne General Hospital. The analysis used Cox proportional modeling to obtain adjusted hazards ratios for hypotension. Results: A total of 806 confirmed patients were included 78 (9.6%) of whom developed hypotension. Extensive purpura, cutaneomucous hemorrhage, serous effusion and age 1-15 years were associated with subsequent hypotension whereas 'aches' and a rash were associated with a lower incidence of hypotension. The biological variables independently associated with hypotension were: increase of hematocrit, low protein concentrations, low sodium concentration and lymphocytes over 1400/ml. A risk score was computed from the scaled Cox model coefficient. Conclusions: From a clinician's perspective, extensive purpura, cutaneomucous hemorrhage, serous effusion, age 1-15 years, hematocrit increase, low protein, low sodium, lymphocytosis and the absence of aches or of a rash, may be important warning signs to predict subsequent hypotension and shock. Over half of the patients with the highest risk score subsequently developed hypotension. The prognostic score had a 48.2% sensitivity with less than 10% of false positives. This score requires external validation before its impact on clinical practice is evaluated.

Rainfall and sloth births in may, Q fever in July, Cayenne, French Guiana.

Q fever in French Guiana is correlated with the rainy season. We found a 1- to 2-month lagged correlation between Q fever incidence and the number of births of three-toed sloth. This result strengthens the hypothesis that the three-toed sloth is the wild reservoir of Q fever in French Guiana.

Later cART initiation in migrant men from sub-Saharan Africa without advanced HIV disease in France.

OBJECTIVE: To compare the time from entry into care for HIV infection until combination antiretroviral therapy (cART) initiation between migrants and non migrants in France, excluding late access to care. METHODS: Antiretroviral-naïve HIV-1-infected individuals newly enrolled in the FHDH cohort between 2002-2010, with CD4 cell counts >200/µL and no previous or current AIDS events were included. In three baseline CD4 cell count strata (200-349, 350-499, ≥ 500/µL), we examined the crude time until cART initiation within three years after enrollment according to geographic origin, and multivariable hazard ratios according to geographic origin, gender and HIV-transmission group, with adjustment for baseline age, enrollment period, region of care, plasma viral load, and HBV/HBC coinfection. RESULTS: Among 13338 individuals, 9605 (72.1%) were French natives (FRA), 2873 (21.4%) were migrants from sub-Saharan Africa/non-French West Indies (SSA/NFW), and 860 (6.5%) were migrants from other countries. Kaplan-Meier probabilities of cART initiation were significantly lower in SSA/NFW than in FRA individuals throughout the study period, regardless of the baseline CD4 stratum. After adjustment, the likelihood of cART initiation was respectively 15% (95%CI, 1-28) and 20% (95%CI, 2-38) lower in SSA/NFW men than in FRA men who had sex with men (MSM) in the 350-499 and ≥ 500 CD4 strata, while no difference was observed between other migrant groups and FRA MSM. CONCLUSION: SSA/NFW migrant men living in France with CD4 >350/µL at entry into care are more likely to begin cART later than FRA MSM, despite free access to treatment. Administrative delays in obtaining healthcare coverage do not appear to be responsible.

Q fever in French Guiana.

Coxiella burnetii, the causative agent of Q fever, is present worldwide. Recent studies have shown that this bacterium is an emerging pathogen in French Guiana and has a high prevalence (24% of community-acquired pneumonia). In this review, we focus on the peculiar epidemiology of Q fever in French Guiana. We place it in the context of the epidemiology of the disease in the surrounding countries of South America. We also review the clinical features of Q fever in this region, which has severe initial presentation but low mortality rates. These characteristics seem to be linked to a unique genotype (genotype 17). Finally, we discuss the issue of the animal reservoir of C. burnetii in French Guiana, which is still unknown. Further studies are necessary to identify this reservoir. Identification of this reservoir will improve the understanding of the Q fever epidemic in French Guiana and will provide new tools to control this public health problem.

Critical importance of long-term adherence to care in HIV infected patients in the cART era: new insights from Pneumocystis jirovecii pneumonia cases over 2004-2011 in the FHDH-ANRS CO4 cohort.

OBJECTIVE: To describe characteristics and outcomes of HIV-infected patients with Pneumocystis jirovecii pneumonia (PCP) over 2004-2011 in France, in particular in those previously enrolled (PE) in the French Hospital Database on HIV (FHDH). METHODS: PE patients with an incident PCP were compared with patients with an inaugural PCP revealing HIV infection (reference). Adequate adherence to care was defined as a CD4 measurement at least every 6 months. Immune reconstitution (CD4≥200/mm3) and risk of death were studied using Kaplan-Meier estimates and multivariable Cox proportional hazards models. RESULTS: In a context of a decreasing incidence of PCP, 1259 HIV-infected patients had a PCP diagnosis, and 593 (47%) were PE patients of whom 161 (27%) have had a prior history of AIDS-defining clinical illness (prior ADI). Median time since enrolment was 8 years for PE patients; 74% had received cART. Median proportion of time with adequate adherence to care was 85% (IQR, 66-96) for all FHDH enrollees, but only 45% (IQR, 1-81) for PE patients during the 2 years before PCP. Median CD4 cell count (38/mm3) and HIV viral load (5.2 log10 copies/ml) at PCP diagnosis did not differ between PE patients and the reference group. Three year mortality rate of 25% was observed for PE prior ADI group, higher than in PE non-prior ADI group (8%) and the reference group (9%) (p<0.0001). In the PE prior ADI group, poor prognosis remained even after adjustment for virological control and immune reconstitution (HR, 2.4 [95%CI, 1.5-3.7]). CONCLUSION: Almost 50% of PCP diagnoses in HIV-infected patients occurred presently in patients already in care, mainly with a previous cART prescription but with waning adherence to care. Having repeated ADI is contributing to the risk of death beyond its impact on immune reconstitution and viral suppression: special efforts must be undertaken to maintain those patients in care.

Comparison between emerging Q fever in French Guiana and endemic Q fever in Marseille, France.

Q fever is an emergent disease in French Guiana. We compared the incidence clinical and serologic profiles between patients from Cayenne, French Guiana and Marseille in metropolitan France during a four-year period. The annual incidence of diagnosed acute Q fever was significantly higher in Cayenne (17.5/100,000) than in Marseille (1.9/100,000) (P = 0.0004), but not the annual incidence of endocarditis (1.29 versus 0.34/100,000). Most patients had fever (97%) and pneumonia (83%) in Cayenne versus 81% and 8% in Marseille (P < 0.0001 and P < 0.0001, respectively) but transaminitis was more common in patients from Marseille (54% versus 32%; P < 0.0001). The proportion of patients with cardiovascular infections was significantly lower in Cayenne (7%) than in Marseille (17%) (P = 0.017), although they showed a stronger immune response with higher levels of phase I IgG (P = 0.024). The differing epidemiology, clinical, and serologic responses of patients from Cayenne and Marseille suggest a different source of infection and a different strain of Coxiella burnetii.

Cohort Profile: French hospital database on HIV (FHDH-ANRS CO4).

The French Hospital Database on HIV (FHDH) is a hospital-based multicentre open cohort with inclusions ongoing since 1989. The research objectives focus mainly on mid- and long-term clinical outcomes and therapeutic strategies, as well as severe AIDS and non-AIDS morbidities, and public health issues relative to HIV infection. FHDH also serves to describe HIV-infected patients receiving hospital care in France. FHDH includes data on more than 120,000 HIV-infected patients from 70 French general or university hospitals distributed throughout France. Patients are eligible for inclusion if they are infected by HIV-1 or HIV-2 and give their written informed consent. Standardized variables are collected at each outpatient visit or hospital admission during which a new clinical manifestation is diagnosed, a new treatment is prescribed or a change in biological markers is noted, and/or at least every 6 months. Since its inception, variables collected in FHDH include demographic characteristics, HIV-related biological markers, the date and type of AIDS and non AIDS-defining events, antiretroviral treatments and the date and causes of death, as reported in the medical records. Since 2005, data have also been collected on: co-infection with hepatitis B or C virus; alcohol and tobacco use; and non HIV-related biomarkers. Anyone can submit a research project by completing a standardized form available on the FHDH website (http://www.ccde.fr/_fold/fl-1385734776-429.pdf) or from the corresponding author, describing the context and objectives of the study. All projects are reviewed by the scientific committee.

Unique clone of Coxiella burnetii causing severe Q fever, French Guiana.

Acute Q fever is an emergent and severe disease in French Guiana. We obtained 5 Coxiella burnetii isolates from samples of patients from Cayenne and found an epidemic clone circulating in Cayenne. This clone has caused pneumonia and endocarditis and seems to be more virulent than previously described strains.