Assessment of current practice for ß-lactam therapeutic drug monitoring in French ICUs in 2021: a nationwide cross-sectional survey.

BACKGROUND: Current guidelines and literature support the use of therapeutic drug monitoring (TDM) to optimize ß-lactam treatment in adult ICU patients. OBJECTIVES: To describe the current practice of ß-lactam monitoring in French ICUs. METHODS: A nationwide cross-sectional survey was conducted from February 2021 to July 2021 utilizing an online questionnaire that was sent as an email link to ICU specialists (one questionnaire per ICU). RESULTS: Overall, 119 of 221 (53.8%) French ICUs participated. Eighty-seven (75%) respondents reported having access to ß-lactam TDM, including 52 (59.8%) with on-site access. ß-Lactam concentrations were available in 24-48 h and after 48 h for 36 (41.4%) and 26 (29.9%) respondents, respectively. Most respondents (n = 61; 70.1%) reported not knowing whether the ß-lactam concentrations in the TDM results were expressed as unbound fractions or total concentrations. The 100% unbound fraction of the ß-lactam above the MIC was the most frequent pharmacokinetic and pharmacodynamic target used (n = 62; 73.0%). CONCLUSIONS: Despite the publication of international guidelines, ß-lactam TDM is not optimally used in French ICUs. The two major barriers are ß-lactam TDM interpretation and the required time for results.

Capnocytophaga zoonotic infections: a 10-year retrospective study (the French CANCAN study).

Zoonotic species of Capnocytophaga genus belong to the oral microbiota of dogs and cats. They may be responsible for serious human infections, mainly after animal bites, with a high mortality rate. In France, only few cases have been reported and no multicenter study has been conducted. Our aim was to describe the French epidemiology of Capnocytophaga zoonosis. We conducted a multicenter (21 centers) retrospective non-interventional, observational study in France describing the epidemiology of Capnocytophaga zoonosis (C. canimorsus, C. cynodegmi, C. canis) over 10 years with regard to clinical and bacteriological data. From 2009 to 2018, 44 cases of Capnocytophaga zoonotic infections were described (C. canimorsus, n = 41; C. cynodegmi, n = 3). We observed an increase (2.5 times) in the number of cases over the study period (from the first to the last 5 years of the study). The most frequent clinical presentations were sepsis (n = 37), skin and soft tissue infections (n = 12), meningitis (n = 8), osteoarticular infections (n = 6), and endocarditis (n = 2). About one-third of patients with sepsis went into septic shock. Mortality rate was 11%. Mortality and meningitis rates were significantly higher for alcoholic patients (p = 0.044 and p = 0.006, respectively). Other comorbidities included smoking, splenectomy, diabetes mellitus, and immunosuppressive therapy are associated to zoonotic Capnocytophaga infection. Eighty-two percent of cases involved contact with dogs, mostly included bites (63%). Despite all isolates were susceptible to the amoxicillin-clavulanic acid combination, three of them were resistant to amoxicillin.

A case of infective endocarditis caused by Arthrobacter woluwensis.

Corynebacteria are rare causative agents of infective endocarditis. This is a reported case of a destructive aorto-mitral infective endocarditis caused by Arthrobacter woluwensis. Microbial identification was achieved by 16S rRNA polymerase chain reaction on valve tissue samples. Outcome was favorable after surgical valve replacement and 4-week antibiotic treatment.

Nocardia takedensis: a newly recognized pathogen responsible for skin and soft tissue infections.

Nocardia takedensis was first isolated in 2005, from soil in Japan. We report here two cases of lymphangitis in France (2012-2017) caused by N. takedensis both occurring after skin injury while gardening, which enabled its inoculation. The two patients were immunocompromised and successfully treated by an antimicrobial agent active on the isolated strain, trimethoprim-sulfamethoxazole and amoxicillin-clavulanic acid for patient one and patient two, respectively. Our study along with previous ones supports the idea of a newly recognized cutaneous opportunistic pathogen and reinforces the recommendation of using gloves during soil exposure for immunocompromised patients. Lastly, according to data found in the literature, we would recommend trimethoprim-sulfamethoxazole as an efficient empirical antibiotic therapy in case of cutaneous infection caused by N. takedensis.

Direct Identification of 80 Percent of Bacteria from Blood Culture Bottles by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry Using a 10-Minute Extraction Protocol.

Matrix-assisted laser desorption ionization-time of flight mass spectrometry is not widely used to identify bacteria directly from positive blood culture bottles (BCBs) because of overlong protocols. The objective of this work was to develop and evaluate a simple extraction protocol for reliable identification from BCBs. The 10-min protocol was applied over a 5-month period. Direct identifications on day 0 were compared with those obtained from colonies on day 1 [log(score) of ≥2]. We evaluated a range of seven log(score) thresholds on day 0 from 1.4 to 2.0 to find the lower confidence score that provides the higher percentage of direct identifications without loss of accuracy. With a log(score) threshold of ≥1.5 at day 0, our protocol allowed us to identify 80% of bacteria in 632 BCBs (96% of Enterobacteriaceae, 95% of Staphylococcus aureus, 92% of enterococci, and 62% of streptococci). At least one bacterial species of the mixture was identified in 77% of the polymicrobial samples. The rapidity and reliability of the protocol were factors in its adoption for routine use, allowing us to save up to 24 h in identifying 80% of the bacteria in the BCBs and, thus, to supply useful information to adapt antibiotic therapy when necessary. We currently provide reliable daily direct identifications of staphylococci, enterococci, Enterobacteriaceae, Pseudomonas aeruginosa, and beta-hemolytic streptococci.

Amoxicillin/clavulanic acid+aminoglycoside as empirical antibiotic treatment in severe community-acquired infections with diagnostic uncertainty.

Diagnostic uncertainty is common in the emergency room and multidrug-resistant bacteria emerge in the community setting, implying to establish the most efficient empirical antibiotic therapy (eEAT). Our aim was to identify such eEAT, considering that in case of DU with severe clinical presentation, most prescribers would propose an empiric combination (EC). The medical dashboard of our ward records prospectively 28 characteristics of each hospitalization including hospitalization motive, final diagnosis, and all antibiotics prescribed. All patients with community-acquired bacteremia (CAB) were included. DU was defined by a discrepancy between suspected diagnosis in the emergency room and final diagnosis. eEAT was defined by in vitro activity of at least one prescribed compound. Finally, independently from the dashboard, we retrospectively compared 2 CTs: amoxicillin/clavulanic acid (AMC)+gentamicin (G) and cefotaxime (3GC)+G. One thousand thirty-four patients with a final diagnosis of CAB were identified from July 2005 to June 2018, including 357 DU (35%) at baseline. eEAT (n = 553) was associated with a trend towards a lower death rate compared to inefficient therapies: 5.4 vs 10.0% (p = 0.053), and effective antibiotic reassessment was the most protective factor against an unfavorable outcome: 0.34 (0.16-0.71). Bacteria involved in case of UD were resistant to AMC+G and to 3GC+G in 8.1% and 12.8% of patients, respectively. Diagnostic uncertainty was a frequent event requiring antibiotic reassessment. As the latter was not systematically realized, the best eEAT is required and AMC+aminoglycoside should be considered.

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.

Improved quality of care for patients infected or colonised with ESBL-producing Enterobacteriaceae in a French teaching hospital: impact of an interventional prospective study and development of specific tools.

The increasing incidence of ESBL-producing Enterobacteriaceae (ESBL-E) in France prompted the publication of national recommendations in 2010. Based on these, we developed a toolkit and a warning system to optimise management of ESBL-E infected or colonised patients in both community and hospital settings. The impact of this initiative on quality of care was assessed in a teaching hospital. The ESBL toolkit was developed in 2011 during multidisciplinary meetings involving a regional network of hospital, private clinic and laboratory staff in Southeastern France. It includes antibiotic treatment protocols, a check list, mail templates and a patient information sheet focusing on infection control. Upon identification of ESBL-E, the warning system involves alerting the attending physician and the infectious disease (ID) advisor, with immediate, advice-based implementation of the toolkit. The procedure and toolkit were tested in our teaching hospital. Patient management was compared before and after implementation of the toolkit over two 3-month periods (July-October 2010 and 2012). Implementation of the ESBL-E warning system and ESBL-E toolkit was tested for 87 patients in 2010 and 92 patients in 2012, resulting in improved patient management: expert advice sought and followed (16 vs 97%), information provided to the patient's general practitioner (18 vs 63%) and coding of the condition in the patient's medical file (17 vs 59%), respectively. Our multidisciplinary strategy improved quality of care for in-patients infected or colonised with ESBL-E, increasing compliance with national recommendations.

Managing ESBL-producing Enterobacteriaceae-related urinary tract infection in primary care: a tool kit for general practitioners.

In Southern France, approximately 4% of E. coli isolates from community-acquired urinary tract infections are extended spectrum beta-lactamase producers, while carriage rates for enterobacteriaceae (ESBL-E) range from 3 to 6%. General practitioners (GP) are unfamiliar with the management of patients harboring ESBL-E. Providing them with a specific tool kit should assist in their therapeutic approach and optimize antimicrobial prescription an ESBL-E tool kit was developed by a multidisciplinary team: infectious diseases (ID) specialists, microbiologists, pharmacologists, and nursing home staff. This tool kit includes treatment protocols, GP and patient information leaflets, a list of infection control measures, and contact details of ID physicians for specialized advice. A community-based (including nursing homes) prospective study was conducted in 2012 in Southeastern France to test the tool kit in the context of ESBL-E-related urinary tract infections (UTI). ESBL-E-related UTI were identified in 88 patients, 66 GPs were contacted by the microbiology laboratory, 56 stated they were offered the tool kit, 48 said they had received it, and 41 stated they had read its contents. Use of the tool kit was significantly correlated with appropriate antibiotic prescription, which concerned 36/39 tool kit users versus 13/20 non-users (p = 0.0125) and 40 GPs expressed an average satisfaction rate of 4.2 on a scale of 0 to 5. Availability of a specific tool for managing patients harboring ESBL-E, now completed with a website, can assist community-based GPs and improve antimicrobial prescription.

Helicobacter bilis-Associated Suppurative Cholangitis in a Patient with X-Linked Agammaglobulinemia.

ᅟ: Helicobacter bilis is a commensal bacterium causing chronic hepatitis and colitis in mice. In humans, enterohepatic Helicobacter spp. are associated with chronic hepatobiliary diseases. PURPOSE: We aimed at understanding the microbial etiology in a patient with X-linked agammaglobulinemia presenting with suppurative cholangitis. METHODS: 16S rDNA PCR directly performed on a liver biopsy retrieved DNA of H. bilis. RESULTS: Clinical outcome resulted in the normalization of clinical and biological parameters under antibiotic treatment by a combination of ceftriaxone, metronidazole, and doxycyclin followed by a 2-week treatment with moxifloxacin and a 2-month treatment with azithromycin. CONCLUSION: In conclusion, these data suggest a specific clinical and microbiological approach in patients with humoral deficiency in order to detect H. bilis hepatobiliary diseases.

Patients with community-acquired bacteremia of unknown origin: clinical characteristics and usefulness of microbiological results for therapeutic issues: a single-center cohort study.

Bacteremia of unknown origin (BUO) are associated with increased mortality compared to those with identified sources. Microbiological data of those patients could help to characterize an appropriate empirical antibiotic treatment before bloodcultures results are available during sepsis of unknown origin. Based on the dashboard of our ward that prospectively records several parameters from each hospitalization, we report 101 community-acquired BUO selected among 1989 bacteremic patients from July 2005 to April 2016, BUO being defined by the absence of clinical and paraclinical infectious focus and no other microbiological samples retrieving the bacteria isolated from blood cultures. The in-hospital mortality rate was 9%. We retrospectively tested two antibiotic associations: amoxicillin-clavulanic acid + gentamicin (AMC/GM) and 3rd generation cephalosporin + gentamicin (3GC/GM) considered as active if the causative bacteria was susceptible to at least one of the two drugs. The mean age was 71 years with 67% of male, 31 (31%) were immunocompromised and 52 (51%) had severe sepsis. Eleven patients had polymicrobial infections. The leading bacterial species involved were Escherichia coli 25/115 (22%), group D Streptococci 12/115 (10%), viridans Streptococci 12/115 (10%) and Staphylococcus aureus 11/115 (9%). AMC/GM displayed a higher rate of effectiveness compared to 3GC/GM: 100/101 (99%) vs 94/101 (93%) (p = 0.04): one Enterococcus faecium strain impaired the first association, Bacteroides spp. and Enterococcus spp. the second. In case of community-acquired sepsis of unknown origin, AMC + GM should be considered.

First isolation of Clostridium indolis in a patient with chronic osteitis: a case report and literature review of human infections related to Clostridium saccharolyticum group species.

Clostridium indolis is an anaerobic spore-forming Gram-positive bacillus belonging to the Clostridium saccharolyticum group. Its clinical significance in human remains poorly known. We describe the first case of osteitis related to C. indolis, identified by MALDI-TOF mass spectrometry and provide a literature review of human infections related to C. saccharolyticum group species.

Epidemic spread of Pandoraea pulmonicola in a cystic fibrosis center.

BACKGROUND: Pandoraea spp. are recently discovered bacteria, mainly recovered from cystic fibrosis (CF) patients, but their epidemiology and clinical significance are not well known. We describe an epidemic spread of Pandoraea pulmonicola from 2009 in our CF center, involving 6 out of 243 CF patients. METHODS: Bacterial identification used amplified ribosomal DNA restriction analysis (ARDRA), MALDI-TOF mass spectrometry (MALDI-TOF MS) and 16S rDNA gene sequencing. The clonal link between strains was assessed with pulsed field gel electrophoresis (PFGE) using XbaI. Clinical data were gathered for all patients. RESULTS: The index case was chronically colonized since 2000. The main hypothesis for this bacterial spread was a droplet cross-transmission, due to preventive measures not being strictly followed. Antibiotic susceptibility testing revealed resistance to beta-lactams, ciprofloxacin and colistin. However, there was susceptibility to trimethoprim-sulfamethoxazole. All patients were chronically colonized with Pseudomonas aeruginosa, and the acquisition of P. pulmonicola resulted in chronic colonization in all patients. Three patients died, and two patients remained clinically stable, whereas one patient had a decline in lung function. CONCLUSIONS: This study, which is the first to describe an epidemic spread of P. pulmonicola, notes the potential transmissibility of this bacterial species and the need for infection control measures.

Infectious endocarditis caused by Helcococcus kunzii in a vascular patient: a case report and literature review.

BACKGROUND: Helcococcus kunzii is a facultative anaerobic bacterium that was first described by Collins et al. in 1993, and was initially considered as a commensal of the human skin, in particular of lower extremities. Human infections caused by H. kunzii remain rare with only a few cases published in the pubmed database. Nevertheless recent reports indicate that this microorganism has to be considered as an opportunistic pathogen that can be involved in severe infections in human. To the best of our knowledge, we describe here the first known case of infectious endocarditis caused by H. kunzii. CASE PRESENTATION: A 79 year-old man reporting severe polyvascular medical history attended the emergency ward for rapid deterioration of his general state of health. After physical examination and paraclinical investigations, the diagnosis of infectious endocarditis on native mitral valve caused by Helcococcus kunzii was established based on Dukes criteria. MALDI-TOF mass spectrometry and 16S rDNA sequencing allowed an accurate identification to the species level of Helcococcus kunzii. The patient was successfully treated by a medico-surgical approach. The treatment consisted in intravenous amoxicillin during four weeks and mitral valve replacement with a bioprosthestic valve. After an in depth review of patient's medical file, the origin of infection remained unknown. However, a cutaneous portal of entry cannot be excluded as the patient and his General Practitioner reported chronic ulcerations of both feet. CONCLUSIONS: We describe here the first case of endocarditis caused by H. kunzii in an elderly patient with polyvascular disease. This report along with previous data found in the literature emphasizes the invasive potential of this bacterial species as an opportunistic pathogen, in particular for patient with polyvascular diseases. MALDI-TOF mass spectrometry and 16S rDNA sequencing are reliable tools for H. kunzii identification. We also sequenced in this work H.kunzii type strain 103932T CIP and deposited in the Genbank under accession number KM403387. We noticed a 14 base difference between our sequence and the original sequence deposited by Collins et al. under Genbank accession number X69837. Hopefully, the spread of next generation sequencing tools would lead to a more accurate classification of clinical strains.

Lumbar discitis caused by Clostridium perfringens.

We report here a rare case of chronic lumbar discitis caused by Clostridium perfringens in an elderly patient that was treated with a combination of ß-lactams and clindamycin. Molecular analysis performed on the strain revealed an unusual toxin gene pattern.

A rare case of histopathological bladder necrosis associated with Actinobaculum schaalii: the incremental value of an accurate microbiological diagnosis using 16S rDNA sequencing.

We describe here a rare case of bladder wall necrosis associated with Actinobaculum schaalii in a 72-year-old patient with non-muscle-invasive bladder cancer (NMIBC). A. schaalii microbiological diagnosis requires high index of suspicion and accurate identification methods such as 16S rDNA sequencing or MALDI-TOF Mass spectrometry.

Impact of revised breakpoints on the categorization of susceptibility of Enterobacterales to temocillin.

Background: To harmonize with the EUCAST breakpoints, the French Society of Microbiology introduced a change in the inhibition diameter breakpoint (17 mm versus 20 mm previously) of temocillin. We assessed the impact of the new breakpoints on categorizing susceptibility of Enterobacterales to temocillin. Methods: This was a multicentric retrospective study including all Enterobacterales isolates routinely tested for temocillin susceptibility with the disc diffusion method between 1 January 2016 and 31 July 2022 in four centres. Categorization using the breakpoints of 20 mm (French guidelines CA-SFM/EUCAST 2020 v.1.1) and 17 mm (French guidelines CA-SFM/EUCAST 2021 v1.0 and EUCAST guidelines v11.0) was performed. Results: Overall, 36 416 Enterobacterales isolates were included. The overall rate of temocillin resistance decreased from 11.3% to 4.7% (relative difference of 58.5%) when using the 17 mm breakpoint instead of the 20 mm breakpoint, respectively. The relative change ranged from -44.0% in Klebsiella aerogenes to -72.7% in Klebsiella oxytoca. The median inhibition diameter was 23 mm (IQR 21-25). The isolates with a diameter of 20 mm appeared overrepresented, whereas those with a diameter of 18 and 19 mm were underrepresented. We therefore reviewed the diameters between 18 and 21 mm of 273 isolates. Thirty-two (11.7%) of them categorized as susceptible at first measure were controlled resistant at second measure. Conclusions: The new breakpoint induced a decrease in the rate of isolates categorized as resistant to temocillin, increasing therapeutic choice including for Extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE). We suggest the bias in measuring the inhibition diameter is probably related to the fact that temocillin is considered remarkably stable against broad-spectrum ß-lactamases.

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.

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.