[Short antibiotic therapy in hospitalized pneumonia: A cohort study]. / Antibiothérapie courte au cours de la pneumonie : PNEUMOSHORT.

INTRODUCTION: Pneumonia is one of the most common indications for antibiotic. Shortening the duration of antibiotic therapy should help reduce bacterial resistance. To date, three randomized control trials have shown non-inferiority of short courses of antibiotic therapy (3 days) compared with 7 days in non-severe pneumonia. The aim of this study was to assess this strategy in real life. METHOD: This retrospective observational cohort study included all patients with pneumonia hospitalized in an internal medical ward from 11/01/2022 to 05/31/2023. We implemented the strategy based on early discontinuation of antibiotic therapy in patients with pneumonia who were clinically stable after 3 days of ß-lactam treatment. RESULTS: Among 49 patients included, median age was 72, median antibiotic duration was 4 days (IQR 3-6), and cure rate at D30 was 88 %. At day 30, we observed one death (2 %), four new antibiotic therapy (9 %), and two new hospitalisation (5 %), among five immunosuppressed patients. Among immunosuppressed patients (n=17; 35 %), failure rate was three times higher in case of short antibiotic courses (3/8; 38 %) than long antibiotic courses (1/7; 14 %). CONCLUSION: Strategy based on early discontinuation of antibiotic therapy in immunocompetent patients with pneumonia who were clinically stable after 3 days of ß-lactam treatment is safe, and easy to implement in a medical ward.

Prognosis of prosthetic valve infective endocarditis due to Streptococcus spp., a retrospective multi-site study to assess the impact of antibiotic treatment duration.

PURPOSE: The duration of antibiotic treatment for prosthetic valve endocarditis caused by Streptococcus spp. is largely based on clinical observations and expert opinion rather than empirical studies. Here we assess the impact of a shorter antibiotic duration. OBJECTIVES: To assess the impact of antibiotic treatment duration for streptococcal prosthetic valve endocarditis on 12-month mortality as well as subsequent morbidity resulting in additional cardiac surgical interventions, and rates of relapse and reinfection. METHODS: This retrospective multisite (N= 3) study examines two decades of data on patients with streptococcal prosthetic valve endocarditis receiving either 4 or 6 weeks of antibiotics. Overall mortality, relapse, and reinfection rates were also assessed for the entire available follow-up period. RESULTS: The sample includes 121 patients (median age 72 years, IQR [53; 81]). The majority (74%, 89/121) received a ß-lactam antibiotic combined with aminoglycoside in 74% (89/121, median bi-therapy 5 days [1; 14]). Twenty-eight patients underwent surgery guided by ESC-guidelines (23%). The 12-month mortality rate was not significantly affected by antibiotic duration (4/40, 10% in the 4-week group vs 3/81, 3.7% in the 6-week group, p=0.34) or aminoglycoside usage (p=0.1). Similarly, there were no significant differences between the 2 treatment groups for secondary surgical procedures (7/40 vs 21/81, p=0.42), relapse or reinfection (1/40 vs 2/81 and 2/40 vs 5/81 respectively). CONCLUSIONS: Our study found no increased adverse outcomes associated with a 4-week antibiotic duration compared to the recommended 6-week regimen. Further randomized trials are needed to ascertain the optimal duration of treatment for streptococcal endocarditis.

Impact of medical and pharmaceutical interventions on anti-infective prescriptions: an observational study.

Appropriate prescribing of anti-infectives is a public health challenge. In our hospital, clinical microbiologists (clinical microbiology mobile unit, UMMc) and clinical pharmacists (clinical pharmacy, PHAc) carry out interventions on anti-infective prescriptions to improve practices. Our main objective was to evaluate the acceptance of UMMc and PHAc interventions on anti-infective prescriptions by quantifying the rate of prescription change 24 h after intervention. The secondary objective was to characterize the type of intervention and associate the rate of change for each. All prescriptions are computerized, and interventions traced via DxCare® software, which feeds a local data warehouse (HEGP-CDW). This descriptive, retrospective, single-center, uncontrolled study was conducted from January 2015 to December 2018. The data were extracted over this period from the data warehouse and analyzed using R software. UMMc interventions were accepted 72.2% of the time and PHA interventions 87.3%. The types of interventions found were mostly dose adjustments (61.1% for the UMMc and 54.2% for the PHAc) and proposals to change or stop a drug. Interventions have an impact on anti-infective prescriptions and are generally followed by clinicians. For the category "discontinuation of a molecule", almost half of the advice from the UMMc was refused. The collaboration between the UMMc and PHAc should be reinforced to improve acceptance.

The multiple benefits of second-generation ß-lactamase inhibitors in treatment of multidrug-resistant bacteria.

The World Health Organisation (WHO) has designated antibiotic resistance as one of the most challenging public health threats of the 21st century. Production of ß-lactamase enzymes by Gram-negative bacteria is the main mechanism of resistance to ß-lactam (BL), the most widely used antibiotic in clinics. In an attempt to neutralise the hydrolytic activity of these enzymes, ß-lactamase inhibitors (BLIs) have been developed. First-generation BLIs include clavulanic acid, sulbactam and tazobactam. However, none of them cover all ß-lactamase classes, and an increasingly wide panel of inhibitor-resistant bacterial strains has developed. Second-generation BLIs function via different mechanisms and were developed by novel scaffolds from which diazabicyclooctane (DBOs) and boronic acids have emerged. In this paper, we provide descriptions of promisor second-generation ß-lactamase inhibitors, such as avibactam, vaborbactam and boronic acids, as well as several BL-BLI combinations that have been designed. While some combinations are now being used in clinical practice, most are presently limited to clinical trials or pre-clinical studies. In this paper, we emphasise the continuous need to develop novel and different BLIs to keep up with the multidrug-resistant bacteria that arise. At this time, however, second-generation BLIs constitute a promising and effective approach.

Aminoglycosides for infective endocarditis: time to say goodbye?

BACKGROUND: Based on experimental studies showing synergism with ß-lactams and glycopeptides, aminoglycosides have long been considered essential in the treatment of infective endocarditis (IE). However, their use is associated with a high risk of renal failure, especially in elderly patients. AIMS: The aim of this narrative review was to summarize the evidence to support reducing or even avoiding the use of aminoglycosides for the treatment of IE. We also analysed data supporting the use of aminoglycosides in specific subgroup of IE patients. SOURCES: PubMed database was searched up to July 2019 to identify relevant studies. CONTENTS: Recent European Guidelines reduced the use of aminoglycosides in IE, no longer recommended in Staphylococcus aureus native-valve IE, and shortened to 2 weeks for IE related to Enterococcus faecalis and streptococci with penicillin MIC >0.125 µg/mL. In addition, an alternative regimen without aminoglycosides (ampicillin or amoxicillin plus ceftriaxone) is proposed for E. faecalis. Observational studies suggested that gentamicin would not be necessary in the case of staphylococcal prosthetic valve IE as long as rifampicin is maintained. Recent clinical studies showed that for streptococcal IE, gentamicin could be restricted to isolates with penicillin MIC >0.5 µg/mL. For the empirical and definitive treatment of E. faecalis IE, amoxicillin or ampicillin plus ceftriaxone may be considered, irrespective of high-level of aminoglycoside resistance. IMPLICATIONS: In a scenario of progressive increase in the age and frailty of IE patients, the use of aminoglycosides can be reduced or avoided in ~90% cases. This should result in reduced incidence of renal failure, an important prognostic factor in IE.

ß LACTA test performance for detection of extended-spectrum ß-lactamase-producing Gram-negative bacilli directly on bronchial aspirates samples: a validation study.

OBJECTIVES: Incidence of extended-spectrum ß-lactamase-producing Gram-negative bacilli (ESBL-PE-GNB)-related infections is worryingly increasing worldwide. ESBL-PE-GNB detection directly on bronchial aspirate samples (BAS) performed for suspected pneumonia may help save empirical carbapenems. Our objectives were to optimize ß-LACTA™ test (BLT) realization and evaluate BLT performance for ESBL-PE-GNB detection directly on BAS. METHODS: We studied BLT technical optimization using BAS of different matrix types spiked with increasing concentrations of CTX-M-15-producing Klebsiella pneumoniae; in vitro validation of BLT diagnostic performance on 17 ESBL enzymes, belonging to CTX-M, SHV, TEM, OXA, GES, VEB and PER groups; and clinical validation of BLT performance on 126 BAS prospectively collected from seven intensive care units. RESULTS: After optimization, BLT detected with 100% sensitivity the presence of CTX-M-15-producing K. pneumoniae spiked in sterile BAS for inoculums upon two or more GNB per field upon microscopic Gram staining examination (MGSE). The BLT accurately detected the 17 ESBLs tested at 106 CFU/mL and all ESBLs except Pseudomonas aeruginosa-related OXA-14 at 104 CFU/mL. Among the 126 BAS of the validation cohort, 21 (17%) gave positive BLT (ten in BAS positive and 11 in BAS negative on MGSE). All BLT-positive BAS grew with ESBL-PE-GNB, including five hyper-L2-producing Stenotrophomonas maltophilia strains. BLT detected ESBL-PE-GNB directly on clinical BAS positive for GNB on MGSE and/or growing with ≥104 CFU/mL with 100% sensitivity, specificity, and positive and negative predictive values. CONCLUSIONS: BLT is an accurate tool for ESBL-PE-GNB detection directly on BAS. Further studies are needed to evaluate the impact of BLT-guided early antimicrobial de-escalation strategies.

ß LACTA testing may not improve treatment decisions made with MALDI-TOF MS-informed antimicrobial stewardship advice for patients with Gram-negative bacteraemia: a prospective comparative study.

PURPOSE: The aim of this study was to assess if use of the ß LACTA test (BLT) for extended-spectrum beta-lactamase (ESBL) detection and/or early bacterial identification by mass spectrometry (MALDI-TOF MS) improves therapeutic decision-making when combined with advice from the antimicrobial stewardship team (AMST) for the management of Gram-negative bacillary (GNB) bacteraemia. METHODS: Prospective observational theoretical study that included patients with GNB bacteraemia during a 6-month period. We compared, against the antimicrobial choice of the local AMST as informed of the Gram-stain result, a hypothetical choice, i.e. one AMST would have made had it been informed of the MALDI-TOF MS results only (option H) with the actual choice AMST made after being informed of the combined MALDI-TOF MS and BLT results (option A).Results/Key findings. A total of 131 episodes of GNB bacteraemia were included. Options H and A led to virtually the same rate of efficient antimicrobial therapy (in 120/131 and 123/131 episodes, respectively, P=0.63). Compared to the gold standard, options H and A did not lead to a significant reduction of carbapenem prescription (9/131, 6/131 and 12/131, P=0.57 and P=0.65, respectively). CONCLUSIONS: Under our test conditions, BLT, when used in conjunction with MALDI-TOF MS and AMST advice, did not allow a significant optimization of the antimicrobial prescription made on the basis AMST advice only. However, the impact of BLT should be evaluated in a population with high prevalence of ESBL-producing Enterobacteriaceae and/or when treatment choices are not made by infectious disease specialists.

International experts' practice in the antibiotic therapy of infective endocarditis is not following the guidelines.

OBJECTIVE: The management of infective endocarditis (IE) may differ from international guidelines, even in reference centres. This is probably because most recommendations are not based on hard evidence, so the consensus obtained for the guidelines does not represent actual practices. For this reason, we aimed to evaluate this question in the particular field of antibiotic therapy. METHODS: Thirteen international centres specialized in the management of IE were selected, according to their reputation, clinical results, original research publications and quotations. They were asked to detail their actual practice in terms of IE antibiotic treatment in various bacteriological and clinical situations. They were also asked to declare their IE-related in-hospital mortality for the year 2015. RESULTS: The global compliance with guidelines concerning antibiotic therapy was 58%, revealing the differences between theoretical 'consensus', local recommendations and actual practice. Some conflicts of interest were also probably expressed. The adherence to guidelines was 100% when the protocol was simple, and decreased with the seriousness of the situation (Staphylococus spp. 54%-62%) or in blood-culture-negative endocarditis (0%-15%) that requires adaptation to clinical and epidemiological data. CONCLUSION: Worldwide experts in IE management, although the majority of them were involved and co-signed the guidelines, do not follow international consensus guidelines on the particular point of the use of antibiotics.

Untargeted next-generation sequencing-based first-line diagnosis of infection in immunocompromised adults: a multicentre, blinded, prospective study.

OBJECTIVE: Infections are the major cause of morbidity and mortality in immunocompromised patients. Improving microbiological diagnosis in these patients is of paramount clinical importance. METHODS: We performed this multicentre, blinded, prospective, proof-of-concept study, to compare untargeted next-generation sequencing with conventional microbiological methods for first-line diagnosis of infection in 101 immunocompromised adults. Patients were followed for 30 days and their blood samples, and in some cases nasopharyngeal swabs and/or biological fluids, were analysed. At the end of the study, expert clinicians evaluated the results of both methods. The primary outcome measure was the detection rate of clinically relevant viruses and bacteria at inclusion. RESULTS: Clinically relevant viruses and bacteria identified by untargeted next-generation sequencing and conventional methods were concordant for 72 of 101 patients in samples taken at inclusion (κ test=0.2, 95% CI 0.03-0.48). However, clinically relevant viruses and bacteria were detected in a significantly higher proportion of patients with untargeted next-generation sequencing than conventional methods at inclusion (36/101 (36%) vs. 11/101 (11%), respectively, p <0.001), and even when the latter were continued over 30 days (19/101 (19%), p 0.003). Untargeted next-generation sequencing had a high negative predictive value compared with conventional methods (64/65, 95% CI 0.95-1). CONCLUSIONS: Untargeted next-generation sequencing has a high negative predictive value and detects more clinically relevant viruses and bacteria than conventional microbiological methods. Untargeted next-generation sequencing is therefore a promising method for microbiological diagnosis in immunocompromised adults.

Neurological deficit secondary to a pre-sacral abscess with epidural extension up to L3: A case report and literature review.

Isolated epidural abscesses are uncommon lesions. Surgical treatment may be difficult due to the extension of these lesions. We present a case of a pelvic abscess spreading along the path of the sciatic nerve to the gluteus muscles and the lumbar canal, causing neurological compression; requiring surgical treatment with three simultaneous approaches.

Analysis of the 2015 American and European guidelines for the management of infective endocarditis.

The optimal management of infective endocarditis requires a broad range of expertise (infectious disease specialists, cardiologists, microbiologists, cardiac surgeons, and intensivists). Given the low level of evidence currently available to support the management of infective endocarditis, international guidelines have always been particularly awaited and rather well implemented. Their cautious analysis of the medical literature and the range of expertise combined within the groups in charge of these guidelines are usually broadly acknowledged and respected. The publications, a few weeks apart, of the 2015 updates of the American and European guidelines, was quite disturbing. Indeed, several discrepancies on major therapeutic propositions were observed, including empirical treatment (penicillin M+penicillin A+gentamicin for Europeans in acutely ill patients; penicillin A+beta-lactamase inhibitor+gentamicin for Americans), or first-line treatment for the most common pathogen responsible for endocarditis in 2016, Staphylococcus aureus (trimethoprim-sulfamethoxazole+clindamycin as an alternative in the European guidelines, while this regimen is not even mentioned in the American guidelines). Other discrepancies were observed, although less significant: the role of positron emission tomography labelled with 18F-fluorodeoxyglucose and administration modalities for aminoglycosides. We aimed to detail the main changes brought upon by these guidelines, their discrepancies, and the 'pros' and 'cons' that may help you select the best treatment regimen for your patients.

Medicinal leech therapy and Aeromonas spp. infection.

While the use of medicinal leech therapy (MLT) in reconstructive and orthopaedic surgery is widely described, post-operative complications related to leeches remain a major concern. Aeromonas spp. strains are involved in the majority of reported cases. As surgical success rate is directly impacted, an adapted antibiotic prophylaxis should be instituted in order to minimize these complications. We assessed pharmaceutical process, microbiological control and related infections in order to provide data and choose the appropriate antibiotherapy for patients requiring MLT. We report a clinical and microbiological study over a 24-month period. Clinical data were collected from patients' database, and microbiological analysis both on leeches' tank water and crushed leeches were performed to characterize isolated strains and their susceptibility to antibiotics. A total of 595 leeches were used to treat 28 patients (12 in plastic surgery and 16 in orthopaedic surgery), and three documented cases of post-operative infections were reported. Aeromonas spp. isolates yielded from 62 % of analyzed batches (75 % of Aeromonas veronii). Eighteen Aeromonas spp. isolates yielded from 23 water samples and three crushed leeches. Isolates were similar in tank and crushed leeches. Strains were susceptible to fluoroquinolones, sulfamethoxazole/trimethoprim, aminosides, and third-generation cephalosporins but resistant to amoxicillin/clavulanic acid and second-generation cephalosporins. According to collected data, routine tank water microbiological analyses are mandatory in order to identify leeches' batches containing resistant strains and to discard them. In this context, the surgeon is able to select an appropriated antibiotic prophylaxis in order to avoid MLT associated serious post-operative complications.

Switch to oral antibiotics in the treatment of infective endocarditis is not associated with increased risk of mortality in non-severely ill patients.

Although many international guidelines exist for the management of infective endocarditis (IE), recommendations are lacking on the opportunity of switching antibiotics from the intravenous (IV) to oral route during treatment. We present a cohort study of 426 cases of IE over a period of 13 years (2000-2012), including 369 cases of definite IE according to the Duke criteria. Predictors of mortality were identified using the Cox proportional hazard analysis. The median (range) age at diagnosis was 64.5 (7-98) years. One hundred six patients (25%) had healthcare-associated IE. Oral streptococci (n = 99, 23%) and Staphylococcus aureus (n = 81, 19%) were the predominant microorganisms. Ninety-two patients (22%) died during follow-up. After an initial phase of IV antibiotherapy, 214 patients (50%) were switched to oral route a median (range) of 21 (0-70) days after diagnosis of IE. Patients in the oral group had fewer comorbidities, and criteria of severity at inclusion and were less frequently infected by S. aureus. Oral antibiotics were amoxicillin alone in 109 cases or a combination therapy of clindamycin, fluoroquinolone, rifampicin and/or amoxicillin in 46 cases, according to the susceptibility of the microorganisms. In the multivariate analysis, a switch to oral route was not associated with an increased risk of mortality. During follow-up, only two relapses and four reinfections were observed in the oral group (compared to nine and eight in the IV group, respectively). In this study, switching to oral administration was not associated with an increased risk of relapse or reinfection. These promising results need to be confirmed by prospective studies.

[Bloodstream infection due to Campylobacter fetus subspecies fetus and skin involvement: A case series of three patients]. / Bactériémie à Campylobacter fetus subspecies fetus et manifestations cutanées : à propos de trois cas.

INTRODUCTION: Among the species of Campylobacter, C. fetus subspecies fetus is characterized by extra-intestinal manifestations, including bloodstream and cardiovascular infections, occurring preferentially in the context of immunosuppression. The cutaneous lesions are rarely described but may be underestimated. CASE REPORTS: We report on 3 cases of cellulitis with bloodstream infection due to Campylobacter fetus subspecies fetus, without cardiovascular infection in a 72- and 85-year-old women, respectively, and a 79-year-old man. Outcome was successful in all 3 cases after prolonged amoxicillin-clavulanic acid treatment, without relapse. CONCLUSION: C. fetus subspecies fetus is rarely associated with skin and soft tissue infections. Cardiovascular complications may be searched in such context.

Chronic endocarditis due to Legionella anisa: a first case difficult to diagnose.

Endocarditis due to Legionella spp. is uncommon but presumably underestimated given the prevalence of Legionellae in the environment. We report a first and unusual case of chronic native valve endocarditis due to L. anisa and advocate that the diagnosis of endocarditis be made collaboratively between the cardiologist, surgeon, microbiologist and pathologist.

Fatal necrotizing fasciitis due to necrotic toxin-producing Escherichia coli strain.

We report a fatal case of necrotizing soft tissues infection caused by an Escherichia coli strain belonging to phylogenetic group C and harbouring numerous virulence factors reported to be part of a pathogenicity island (PAI) such as PAI IIJ96 and conserved virulence plasmidic region.

Efficacy of tobramycin aerosol in nasal polyposis.

CONTEXT: Treatment of infected nasal polyposis. MATERIAL AND METHODS: Multicenter interventional prospective double-blind randomized study with matched groups: treatment with tobramycin aerosol versus isotonic saline aerosol. The study population included 55 patients: 23 receiving isotonic saline aerosol and 32 receiving tobramycin. A novel device (Easynose®) was used with an original principle limiting pulmonary deposition and ensuring homogeneous peripheral deposition in the nasal cavities. OBJECTIVES: The principal objective was to compare bacteriological eradication between tobramycin 150mg/3ml versus isotonic saline, both administered by nebulization via the Easynose® device. RESULTS AND CONCLUSION: Tobramycin aerosol administered via the Easynose® device showed significantly better bacteriological eradication than isotonic saline.

Postprescription review improves in-hospital antibiotic use: a multicenter randomized controlled trial.

Although review of antibiotic therapy is recommended to optimize antibiotic use, physicians do not always perform it. This trial aimed to evaluate the impact of a systematic postprescription review performed by antimicrobial stewardship program (ASP) infectious disease physicians (IDP) on the quality of in-hospital antibiotic use. A multicenter, prospective, randomized, parallel-group trial using the PROBE (Prospective Randomized Open-label Blinded Endpoint) methodology was conducted in eight surgical or medical wards of four hospitals. Two hundred forty-six patients receiving antibiotic therapy prescribed by ward physicians for less than 24 hours were randomized to receive either a systematic review by the ASP IDP at day 1 and days 3 to 4 (intervention group, n = 123) or no systematic review (usual care, n = 123). The primary outcome measure was appropriateness of antimicrobial therapy, a composite score of appropriateness of antibiotic use at days 3 to 4 and appropriate treatment duration, adjudicated by a blinded committee. Analyses were performed on an intention-to-treat basis. In the intervention group, appropriateness of antimicrobial therapy was more frequent (55/123, 44.7% vs. 35/123, 28.5%; odds ratio 2.03, 95% confidence interval 1.20-3.45). Antibiotic treatment duration was lower in the intervention group (median (interquartile range) 7 (3-9) days vs. 10 (7-12) days; p 0.003). ASP IDP counseling to change therapy was more frequent at days 3 to 4 than at day 1 (114/123; 92.7% vs. 24/123; 19.5%, p <0.001). Clinical outcome was similar between groups. This study suggests that a systematic postprescription antibiotic review performed at days 1 and 3 to 4 results in higher quality of antibiotic use and lower antibiotic duration. This trial was registered at ClinicalTrials.gov (NCT01136200).