First report of Acinetobacter pittii acute community-acquired pneumonia in an immunocompetent patient in France following a heat wave.

BACKGROUND: In recent years, Acinetobacter baumannii-calcoaceticus complex (ABC) infections have attracted attention, mainly because of the impact of carbapenem-resistant isolates in hospital-acquired infections. However, acute community-acquired ABC infections are not uncommon in warm and humid countries, where they are responsible for community-acquired infections with specific clinical features. To date, such infection has not been reported in France. CASE PRESENTATION: We report the case of a 55-year-old non-immunocompromised patient living in France with no known risk factors for community-acquired ABC infections who presented pneumonia with bloodstream infection due to wild-type A. pittii. The outcome was favorable after 7 days of antibiotic treatment with cefepime. We confirmed bacterial identification with whole-genome sequencing, and we examined the A. pitii core-genome phylogeny for genomic clusters. CONCLUSIONS: This situation is uncommon in Europe and occurred after a heat wave in France with temperatures above 38 °C. Herein, we discuss the possibility that this pneumonia may be emerging in the current context of global warming.

Multivariate joint model under competing risks to predict death of hospitalized patients for SARS-CoV-2 infection.

During the coronavirus disease 2019 (COVID-19) pandemic, several clinical prognostic scores have been proposed and evaluated in hospitalized patients, relying on variables available at admission. However, capturing data collected from the longitudinal follow-up of patients during hospitalization may improve prediction accuracy of a clinical outcome. To answer this question, 327 patients diagnosed with COVID-19 and hospitalized in an academic French hospital between January and July 2020 are included in the analysis. Up to 59 biomarkers were measured from the patient admission to the time to death or discharge from hospital. We consider a joint model with multiple linear or nonlinear mixed-effects models for biomarkers evolution, and a competing risks model involving subdistribution hazard functions for the risks of death and discharge. The links are modeled by shared random effects, and the selection of the biomarkers is mainly based on the significance of the link between the longitudinal and survival parts. Three biomarkers are retained: the blood neutrophil counts, the arterial pH, and the C-reactive protein. The predictive performances of the model are evaluated with the time-dependent area under the curve (AUC) for different landmark and horizon times, and compared with those obtained from a baseline model that considers only information available at admission. The joint modeling approach helps to improve predictions when sufficient information is available. For landmark 6 days and horizon of 30 days, we obtain AUC [95% CI] 0.73 [0.65, 0.81] and 0.81 [0.73, 0.89] for the baseline and joint model, respectively (p = 0.04). Statistical inference is validated through a simulation study.

Ampicillin-susceptible Enterococcus faecium infections: clinical features, causal clades, and contribution of MALDI-TOF to early detection.

Enterococcus faecium, a common resident of the human gastrointestinal tract, is also a major pathogen. Prompt initiation of appropriate treatment is essential to improve patient outcome in disseminated E. faecium infections. However, ampicillin resistance is frequent in this species, rendering treatment difficult. We used a comprehensive approach, including clinical data review, whole-genome sequencing, and mass spectrometry, to characterize ampicillin-susceptible (EFM-S) and ampicillin-resistant (EFM-R) isolates. We included all patients with culture-confirmed E. faecium infection attending our hospital over a 16-month period. A comparison of 32 patients infected with EFM-S strains and 251 patients infected with EFM-R strains revealed that EFM-R isolates were strongly associated with a longer hospital stay, history of prior hospitalization, and the carriage of multidrug-resistant organisms. An analysis of the genomes of 26 EFM-S and 26 EFM-R isolates from paired patients revealed a population structure almost perfectly matching ampicillin susceptibility, with resistant isolates in clade A1, and susceptible isolates in clades A2 and B. The clade B and A2 isolates mostly came from digestive or biliary tract samples, whereas clade A1 isolates were mostly obtained from urine and blood. Finally, we built a custom database for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), which differentiated between clade B and clade A1/A2 strains with high-positive and high-negative predictive values (95.6% and 100%, respectively). This study provides important new insight into the clinical features and clades associated with EFM-S and EFM-R isolates. In combination with MALDI-TOF MS, these data could facilitate the rapid initiation of the most appropriate treatment.IMPORTANCEEnterococcus faecium is an important human pathogen in which the prevalence of ampicillin resistance is high. However, little is known about the clinical characteristics of patients infected with ampicillin-resistant and ampicillin-susceptible strains. Indeed, current knowledge is based on genus-wide studies of Enterococcus or studies of very small numbers of susceptible isolates, precluding robust conclusions. Our data highlight specific clinical features related to the epidemiology of EFM-S and EFM-R strains, such as length of hospital stay, history of prior hospitalization, carriage of multidrug-resistant organisms, and type of sample from which the isolate was obtained. The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry with a custom-built database may make it possible to distinguish clade B isolates, which are typically susceptible to ampicillin, from clade A1/A2 isolates (A1 being typically resistant), thereby facilitating the management of these infections.

Evaluation of the contribution of shotgun metagenomics in the microbiological diagnosis of liver abscesses.

BACKGROUND: Shotgun metagenomics (SMg) sequencing has gained a considerable interest, as it enables the detection of any microorganisms through a single analysis. Due to the limitations of standard microbiological approaches, the microbial documentation of liver abscesses (LA), which is crucial for their medical management, can be difficult. Here we aimed to compare the performance of SMg with standard approaches for the microbiological documentation of LA. METHODS: In this retrospective study conducted at two centers, we compared the results of standard microbiology with metagenomics analysis of consecutive LA samples. For samples tested positive for Klebsiella pneumoniae, we compared the analysis of virulence and resistance genes using metagenomics data to whole-genome sequencing of corresponding isolates obtained in culture. RESULTS: Out of the 62 samples included, standard approaches and SMg yielded documentation in 80.6% and 96.8%, respectively. In 37.1% (23/62) of cases, both methods showed identical results, whereas in 43.5% (27/62) of cases, the samples were positive by both methods, but SMg found additional species in 88.9% (24/27), mostly anaerobes. When the standard approaches were negative, the SMg was able to detect microorganisms in 80.0% of cases (8/10). Overall, SMg identified significantly more microorganisms than culture (414 vs.105; p<0.05). K. pneumoniae genome analysis was able to detect resistance and virulence genes with a level of sensitivity depending on the depth of sequencing. DISCUSSION: Overall, we showed that SMg had better performance in detecting and identifying microorganisms from LA samples and could help characterizing strain's resistome and virulome. Although still costly and requiring specific skills and expensive equipment, MGs methods are set to expand in the future.

Severe long-delayed malaria caused by Plasmodium malariae in an elderly French patient.

BACKGROUND: Plasmodium malariae is the cause of the rare but severe form of malaria that sometimes affects individuals travelling to malaria-endemic regions. This report presents the unique case of a patient exhibiting severe malaria symptoms caused by P. malariae with no record of recent travel to any malaria-endemic areas. CASE PRESENTATION: An 81-year-old French woman was admitted to the emergency department with sustained fever and severe weakness for the past 5 days. She suffered from anaemia, thrombocytopenia, confusion, somnolence, pulmonary complications, and hypoxaemia. In the absence of any concrete aetiology that could explain the fever together with thrombocytopenia, physicians suspected malaria as a probable diagnosis. The LAMP-PCR and lateral flow test confirmed the presence of malaria parasite, Plasmodium sp. Microscopic examination (May-Grünwald Giemsa-stained thin blood smear) revealed the presence of trophozoites, schizonts, and gametocytes with 0.93 % parasitaemia. Conventional PCR amplification targeting 510 bp DNA fragment of small subunit ribosomal RNA (ssrRNA) and bidirectional sequencing identified the parasite as Plasmodium malariae. The travel history of this patient revealed her visits to several countries in Europe (Greece), North Africa (Tunisia and Morocco), and the West Indies (Dominican Republic). Of these, the latter was the only country known to be endemic for malaria at the time (three malaria parasite species were prevalent: Plasmodium falciparum, Plasmodium vivax, and P. malariae). The patient had most likely got infected when she visited the Dominican Republic in the summer of 2002. This time interval between the initial parasite infection (2002) till the onset of symptoms and its subsequent diagnosis (2020) is a reminder of the ability of P. malariae to persist in the human host for many years. CONCLUSIONS: This report highlights the persistent nature and ability of P. malariae to cause severe infection in the host even after a prolonged time interval.

Urinary tract infection and antibiotic use around ureteral stent insertion for urolithiasis.

Urolithiasis is the main indication for a ureteral JJ stent. Our aim was to determine the incidence of urinary tract infections (UTIs) after a JJ stent for urolithiasis, with an emphasis on antibiotic use. Prospective, multicenter, cohort study over a 4-month period including all of the patients with urolithiasis requiring JJ stent insertion. The clinical and microbiological data and therapeutic information were recorded until removal of the JJ stent. Two hundred twenty-three patients at five French private hospitals were included. A urine culture was performed for 187 patients (84%) prior to insertion of a JJ stent, 36 (19%) of which were positive. One hundred thirty patients (58%) received an antibiotic therapy during surgery: 74 (33%) prophylaxis and 56 (25%) empirical antibiotic therapy, comprising 17 different regimens. The rate of prophylaxis varied according to the center, from 0 to 70%. A total of 208 patients were followed-up until removal of the first stent. The rate of UTIs was 6.3% (13/208); 8.1% of the patients who did not receive a prophylaxis had a UTI versus 1.4% of those who did receive a prophylaxis (p = 0.057). Seven empirical antibiotic regimens were used to treat these 13 patients. Another large panel of antibiotic prescriptions was observed at the time of JJ stent removal. The incidence of a UTI after JJ stent insertion for urolithiasis was 6.3%, in part due to a lack of prophylaxis. An unwarranted diversity of antibiotic use was observed at each step of care.

Antibiotic therapy for Enterococcus bacteraemia: warning for the antimicrobial stewardship team.

Enterococci are a significant cause of bacteraemia in healthcare-associated infections (HCAI), being resistant to cephalosporins and aminoglycosides often used in this setting. Our aim was to measure the rate of inefficient antimicrobial therapy and its impact on the outcome. We conducted a retrospective multicentre cohort study in 6 French institutions. Patients were identified through the laboratory's database, which extracted all positive blood cultures for Enterococcus spp. in 2016. Patients' data were gathered by reviewing hospital records. Efficient antimicrobial therapy was defined as any therapy containing at least one antibiotic compound with in vitro efficacy against Enterococcus spp.: amoxicillin, amoxicillin/clavulanic acid, piperacillin, piperacillin/tazobactam, imipenem, meropenem, vancomycin, daptomycin, linezolide, tigecycline. A short-term unfavourable outcome was defined as intensive care requirement and/or in-hospital death at least 48 h after positive blood culture. One hundred thirty-one patients were included; the main diagnosis was a urinary tract infection (46%) and a HCAI was observed in 54% of the cases. Four patients did not receive any antibiotic. Forty-three per cent of empirical antibiotic therapies and 17% of documented ones were inefficient for enterococcal bacteraemia. Sixty patients (46%) received amoxicillin as a documented therapy. Twenty-three per cent of the patients presented a short-term unfavourable outcome. Univariate and multivariate analyses showed that not receiving amoxicillin as a documented antibiotic therapy was associated with an unfavourable short-term outcome (p = 0.001). In conclusion, Enterococcal bacteraemia was associated with a high proportion of inefficient antimicrobial therapy. In multivariate analysis, amoxicillin use was associated with a better outcome.