Management of patients with pulmonary mycobacteriosis in France: a multicenter retrospective cohort study.

BACKGROUND: Recent studies report very low adherence of practitioners to ATS/IDSA recommendations for the treatment of nontuberculous mycobacteria pulmonary disease (NTM-PD), as well as a great variability of practices. Type of management could impact prognosis. METHODS: To evaluate management and prognosis of patients with NTM-PD cases with respect to ATS recommendations, we conducted a multicenter retrospective cohort study (18 sentinel sites distributed throughout France), over a period of six years. We collected clinical, radiological, microbiological characteristics, management and outcome of the patients (especially death or not). RESULTS: 477 patients with NTM-PD were included. Respiratory comorbidities were found in 68% of cases, tuberculosis sequelae in 31.4% of patients, and immunosuppression in 16.8% of cases. The three most common NTM species were Mycobacterium avium complex (60%), M. xenopi (20%) and M. kansasii (5.7%). Smear-positive was found in one third of NTM-PD. Nodulobronchiectatic forms were observed in 54.3% of cases, and cavitary forms in 19.1% of patients. Sixty-three percent of patients were treated, 72.4% of patients with smear-positive samples, and 57.5% of patients with smear-negative samples. Treatment was in adequacy with ATS guidelines in 73.5%. The 2-year mortality was 14.4%. In the Cox regression, treatment (HR = 0.51), age (HR = 1.02), and M. abscessus (3.19) appeared as the 3 significant independent prognostic factors. CONCLUSION: These findings highlight the adequacy between French practices and the ATS/IDSA guidelines. Treatment was associated with a better survival.

Amino Acid Substitutions Account for Most MexS Alterations in Clinical nfxC Mutants of Pseudomonas aeruginosa.

Multidrug-resistant mutants ofPseudomonas aeruginosathat overproduce the active efflux system MexEF-OprN (callednfxCmutants) have rarely been characterized in the hospital setting. Screening of 221 clinical strains exhibiting a reduced susceptibility to ciprofloxacin (a substrate of MexEF-OprN) and imipenem (a substrate of the negatively coregulated porin OprD) led to the identification of 43 (19.5%)nfxCmutants. Subsequent analysis of 22 nonredundant mutants showed that, in contrast to theirin vitro-selected counterparts, only 3 of them (13.6%) harbored a disruptedmexSgene, which codes for the oxidoreductase MexS, whose inactivation is known to activate themexEF-oprNoperon through a LysR-type regulator, MexT. Nine (40.9%) of the clinicalnfxCmutants contained single amino acid mutations in MexS, and these were associated with moderate effects on resistance and virulence factor production in 8/9 strains. Finally, the remaining 10 (45.5%)nfxCmutants did not display mutations in any of the regulators known to controlmexEF-oprNexpression (themexS,mexT,mvaT, andampRgenes), confirming that other loci are responsible for pump upregulation in patients. Collectively, these data demonstrate thatnfxCmutants are probably more frequent in the hospital than previously thought and have genetic and phenotypic features somewhat different from those ofin vitro-selected mutants.

Evolving epidemiology and antimicrobial resistance in spontaneous bacterial peritonitis: a two-year observational study.

BACKGROUND: Current recommendations for empirical antimicrobial therapy in spontaneous bacterial peritonitis (SBP) are based on quite old trials. Since microbial epidemiology and the management of patients have changed, whether these recommendations are still appropriate must be confirmed. METHODS: An observational study that exhaustively collected the clinical and biological data associated with positive ascitic fluid cultures was conducted in four French university hospitals in 2010-2011. RESULTS: Two hundred and sixty-eight documented positive cultures were observed in 190 cirrhotic patients (median age 61.5 years, 58.5% Child score C). Of these, 57 were classified as confirmed SBP and 140 as confirmed bacterascites. The predominant flora was Gram-positive cocci, whatever the situation (SBP, bacterascites, nosocomial/health-care related or not). Enteroccocci (27.7% E. faecium) were isolated in 24% of the episodes, and in 48% from patients receiving quinolone prophylaxis. E. coli were susceptible to amoxicillin-clavulanate and to third-generation cephalosporins in 62.5% and 89.5% of cases, respectively. No single antibiotic allowed antimicrobial coverage of more than 60%. Only combinations such as amoxicillin + third-generation cephalosporin or cotrimoxazole allowed coverage close to 75-80% in non-nosocomial episodes. Combinations based on broader spectrum antibiotics should be considered for empirical therapy of nosocomial infections. CONCLUSIONS: Our study confirmed the changing spectrum of pathogens in SBP and bacterascites, and the need for more complex antibiotic strategies than those previously recommended. Our findings also underline the need for new clinical trials conducted in the current epidemiological context.

Characteristics and outcomes of cerebrospinal fluid shunt and drain-associated infections.

INTRODUCTION: Data on infections associated with cerebrospinal fluid shunt (CSF-S) or device-associated infection (CSF-SDI) are limited in adults. We performed a retrospective study to describe characteristics, management, and outcome of CSF-SDI. METHODS: All patients with CSF-SDI and admitted to our institution from January 2013 to December 2019 were included. RESULTS: Among 50 patients, fifty-six episodes of CSF-SDI (41 external ventricular device-associated infections (CSF-D) and 15 other shunt infections (CSF-S) were included. The incidence of CSF-SDI was 11.9 %. Fever was the most common symptom (81 %). Enterobacterales were more prevalent in CSF-S than in CSF-D (20 % vs 53 %, p = 0.02). As regards CSF-D, deceased patients (11/41, 27 %) more frequently had a Glasgow coma scale score decreasing from baseline (p < 0.01), lower glycorrhachia (p < 0.01), a higher protein level in CSF (p = 0.001) and a positive control CSF culture (p = 0.031). CONCLUSIONS: CSF-SDIs are rare but with a high mortality rate. Mortality was more closely related to the infection than to comorbidities or underlying neurosurgical disease. A second CSF analysis significantly helped to detect patients with CSF-D with a poor prognosis.

One-stage revision hip arthroplasty for infection using primary cementless stems as first-line implants: About 35 cases.

INTRODUCTION: During infected total hip arthroplasty revisions (THAR), the need for systematic antibiotic cementation remains undefined. HYPOTHESIS: Implantation of a primary cementless stem as first-line implant in 1-stage septic THAR provides results as good as those from a stem cemented with antibiotics in terms of infection resolution. MATERIALS AND METHODS: We retrospectively examined 35 patients operated on for septic THAR with Avenir® cementless stem placement - between 2008 and 2018 at Besançon University Hospital - with a minimum follow-up of 2 years to define healing in the absence of infectious recurrence. Clinical outcomes were assessed using the Harris, Oxford, and Merle D'Aubigné scores. Osseointegration was analyzed by the Engh radiographic score. RESULTS: The median follow-up was 5±2.6 years (2-11). The infection was cured in 32 of 35 (91.4%) patients. The median scores of the following were: Harris 77/100, Oxford 47.5/60 and Merle d'Aubigné 15/18. Of 32 femoral stems, 31 (96.8%) had radiographically stable osseointegration. Age greater than 80 years was a risk factor for failure to cure the infection during septic THAR. DISCUSSION: A primary cementless stem as first-line implant plays a role in 1-stage septic THAR. It confers good results in terms of infection resolution and stem integration in the setting of loss of femoral bone substances rated Paprosky 1. LEVEL OF EVIDENCE: IV; retrospective case series.

Factors associated with late microbiological documentation of prosthetic joint infection.

Purpose: To describe the number of prosthetic joint infections (PJIs) with late documentation and to identify associated factors. Methods: Bacterial PJIs with surgical management between November 2015 and November 2019 in a French center were analyzed. Results of short (72 h) and late culture (at 14 days) were analyzed. Results: A total of 160 PJIs were reported with 215 bacteria. Twenty-nine patients had late documentation (18.1%). The bacteria most involved were coagulase-negative staphylococci and Cutibacterium spp. (60%). In multivariate analysis, late chronic PJI (odds ratio = 2.47) and antibiotic therapy before surgery (odds ratio = 3.13) were associated with late-documented infection. Conclusion: A better knowledge of the factors associated with late-documented infections is essential in order to simplify antibiotic treatment at the appropriate time.

Prosthetic joint infections (PJIs) are rare and occur in around 1% of cases. They are often complex and require multidisciplinary management. The identification of bacteria and the implementation of an effective intravenous antibiotic therapy as soon as the surgery is performed are important points in PJI management. Some bacteria take longer to be cultivated, which is why samples are cultured for at least 14 days after surgery. As soon as the bacteria have been identified, the antibiotic therapy can be taken orally to allow the patient to be discharged early from hospital. The aim of this study was to investigate the factors associated with a positive late culture (day 14 after surgery) compared with an early culture (day 3). We showed that patients who had received antibiotic therapy within 1 month before surgery and patients with chronic PJI (i.e., more than 1 year after surgery) were at greater risk of having long-culture-positive specimens. We also showed that late samples were more often positive for two types of bacteria (Cutibacterium acnes and coagulase-negative staphylococci). In practice, when early samples are positive, oral antibiotics are given rapidly, except for patients who have had prior antibiotic therapy or who have a chronic infection for whom other samples may be positive late (14 days). Moreover, in patients with negative early culture, oral antibiotic therapy active against Cutibacterium acnes and coagulase-negative staphylococci (the two main bacteria in late culture) could be prescribed, waiting for the result of late culture.

Role of the MexEF-OprN efflux system in low-level resistance of Pseudomonas aeruginosa to ciprofloxacin.

In this study, we investigated the resistance mechanisms to fluoroquinolones of 85 non-cystic fibrosis strains of Pseudomonas aeruginosa exhibiting a reduced susceptibility to ciprofloxacin (MICs from 0.25 to 2 µg/ml). In addition to MexAB-OprM (31 of 85 isolates) and MexXY/OprM (39 of 85), the MexEF-OprN efflux pump (10 of 85) was found to be commonly upregulated in this population that is considered susceptible or of intermediate susceptibility to ciprofloxacin, according to current breakpoints. Analysis of the 10 MexEF-OprN overproducers (nfxC mutants) revealed the presence of various mutations in the mexT (2 isolates), mexS (5 isolates), and/or mvaT (2 isolates) genes, the inactivation of which is known to increase the expression of the mexEF-oprN operon in reference strain PAO1-UW. However, these genes were intact in 3 of 10 of the clinical strains. Interestingly, ciprofloxacin at 2 µg/ml or 4 µg/ml preferentially selected nfxC mutants from wild-type clinical strains (n = 10 isolates) and from first-step mutants (n = 10) overexpressing Mex pumps, thus indicating that MexEF-OprN represents a major mechanism by which P. aeruginosa may acquire higher resistance levels to fluoroquinolones. These data support the notion that the nfxC mutants may be more prevalent in the clinical setting than anticipated and strongly suggest the involvement of still unknown genes in the regulation of this efflux system.

Bacterial epidemiology and antimicrobial resistance in ascitic fluid: a 2-year retrospective study.

The bacterial epidemiology of bacterascites and spontaneous bacterial peritonitis is evolving. Four hundred and eleven strains isolated from ascites in cirrhotic patients from 5 French hospitals were isolated in 2006 and 2007. Of these, 114 were definitely associated with spontaneous bacterial peritonitis. The proportion of Gram-positive and Gram-negative agents was quite similar, even after excluding coagulase-negative staphylococci, or when considering only definite spontaneous bacterial peritonitis or community-acquired strains. Staphylococci and Escherichia coli were the most frequent pathogens, but enterococci were also involved in nearly 15% of the cases. Among the E. coli, 28% were intermediate or resistant to amoxicillin+clavulanate, 5.3% expressed cephalosporinases or extended beta-lactamases and 17.3% were intermediate or resistant to fluoroquinolones. Resistance to methicillin was observed in 27% of Staphylococcus aureus. Cefotaxime and amoxicillin-clavulanate remained the most effective 'single' agents, however on less than 70% of isolates. Some combinations (such as cefotaxime+amoxicillin) extended coverage to a further 15% of strains. Since inadequate empiric antibiotic therapy is associated with increased mortality, these combinations may be of great interest as first-line treatment, even though they may also lead to the development of antimicrobial resistance. Repeated epidemiological surveys and new clinical trials are thus needed.

Surgical antibiotic prophylaxis compliance in a university hospital.

OBJECTIVE: To assess surgical antibiotic prophylaxis (SAP) practices in a university hospital in order to identify risk factors associated with non-compliance. STUDY DESIGN: Retrospective monocentric study conducted over a 4-month period. PATIENTS AND METHODS: Data were collected from the software used in the operating theatre. Practice non-compliance was evaluated in comparison with the 2010 version of the French national recommendations. We only took in account the interventions identified as priority surveillance interventions according to the surgical site infections national surveillance. The risk factors associated with SAP non-compliance were identified with a multivariate statistical analysis. RESULTS: We evaluated 1312 SAPs. Among the 1298 indicated SAPs, 44.4% were not compliant. The most frequent inappropriate criterion was the timing of injection (34.8% non-compliance), which was, in the majority of cases, too close to the time of incision. Other inappropriate criteria were identified: antibiotic choice for patients allergic to ß-lactams (inappropriate among 45% of allergic patients), and antibiotic dosing for obese patients (96% of non-compliance). Obesity (OR=84.32), allergy to ß-lactams (OR=17.11) and certain types of surgery (digestive, OR=4.56; gynaecological and obstetrical, OR=7.10; urological, OR=3.95) were independently associated with the non-compliance of SAP practices. CONCLUSION: Improvement measures that target the timing of injection, obese or allergic patients are necessary.