[Original strategy for prevention of recurrent symptomatic urinary tract infections in patients with neurogenic bladder: Bacterial interference, state of the art]. / Stratégie préventive originale des infections urinaires symptomatiques chez les patients porteurs d'une vessie neurologique : l'interférence bactérienne, état de l'art.

PURPOSE: Urinary tract infection (UTI) is the most common complication in patients with neurogenic bladder. The long-term use of antibiotic drugs induces an increase in antimicrobial resistance and adverse drug reactions. Bacterial interference is a new concept to prevent recurrent UTI which consists in a bladder colonization with low virulence bacteria. We performed a literature review on this emerging therapy. MATERIALS AND METHODS: Literature review of bacterial interference to prevent symptomatic urinary tract infection in neurological population. RESULTS: Seven prospectives study including 3 randomized, double-blind and placebo controlled trial were analyzed. The neurological population was spinal cord injured in most cases. The bladder colonization was performed with 2 non-pathogen strains of Escherichia coli: HU 2117 and 83972. At 1 month, 38 to 83% of patients were colonized. Mean duration of colonization was 48.5 days to 12.3 months. All studies showed that colonization might reduce the number of urinary tract infections and is safe with absence of serious side effects. CONCLUSION: Bacterial interference is a promising alternative therapy for the prevention of recurrent symptomatic urinary tract infections in neurogenic patients. This therapy should have developments for a daily use practice and for a long-term efficacy.

Contribution of echocardiography in the diagnosis of definitive infective endocarditis: the infectious disease specialist's point of view.

In 1994, the original Duke criteria introduced the usefulness of echocardiography for the diagnosis of definitive infective endocarditis (IE). Recently, the European Society of Cardiology (ESC) highlighted the need of complementary imaging to support the diagnosis of embolic events and cardiac involvement when echocardiography findings are negative or doubtful. We decided to study the usefulness of transthoracic and transesophageal echocardiography (TTE/TEE) for the diagnosis of definitive IE in patients who already benefited from complementary investigations. A retrospective bicentric study was conducted among patients hospitalized for an IE (2006-2017). Modified Duke criteria were calculated for each patient before and after findings of TTE/TEE. Thereafter, patients were classified by the local task force into three groups: excluded, possible, and definitive IE. Overall, 86 episodes were studied. The median patient age was 72 years (18-95). Microorganisms involved were mostly Staphylococcus aureus (32.5%) and Streptococcus spp. (40.7%). The mortality rate was 17.4%. Before echocardiography, there were 3 excluded IE (3.5%), 51 possible IE (59.3%), and 32 definitive IE (37.2%). After echocardiography findings, we observed 62 definitive (72.1%) and 24 possible IE (27.9%) (p < 0.0001). Our cohort revealed that 19.8% of the definitive and possible IE had a normal echocardiography. The rate of septic emboli did not statistically differ between patients who had a contributive or a normal echocardiography (76.5% vs. 76.8%). TTE and TEE play a major role in the diagnosis of definitive IE, even if we consider findings of complementary imaging. Physicians should be wary that definitive IE may present with a non-contributive echocardiography, mentioned as normal.

Is 5 days of oral fluoroquinolone enough for acute uncomplicated pyelonephritis? The DTP randomized trial.

The treatment duration of acute uncomplicated pyelonephritis (AUP) is still under debate. As shortening treatment duration could be a means to reduce antimicrobial resistance, we aimed to establish whether 5 days of antibiotic treatment is non-inferior to 10 days in patients with AUP. We performed an open-label prospective randomized trial comparing 5 days to 10 days of fluoroquinolone treatment for AUP. The inclusion criteria were: female patients aged ≥18 years with clinical signs of urinary tract infection, fever >38 °C, and positive urinalysis. Patients were randomized to either 5 or 10 days of fluoroquinolone treatment. Outcome was cure at day 10 and day 30 after the end of treatment. One hundred patients were randomized and 12 were excluded after randomization. The mean ± standard deviation (SD) age was 31.8 ± 11 years old and the mean ± SD temperature was 38.6 ± 0.7 °C. The main bacterium involved was Escherichia coli (n = 86; 97.7%) and 3 (3.4%) patients had a positive blood culture. In the post-hoc analysis, clinical cure 10 days after the end of the treatment was 28/30 (93.3%) in the 5-day arm and 36/38 (94.7%) in the 10-day arm (p = 1.00). At day 30, the clinical cure rate was 23/23 (100%) in the 5-day arm and 20/20 (100%) in the 10-day arm (p = 1.00). The microbiological cure rate was 20/23 (87.0%) in the 5-day arm and 16/20 (80.0%) in the 10-day arm (p = 1.00). The efficacy of 5 days of fluoroquinolone treatment does not seem different from 10 days of treatment for AUP.

Outcome of bloodstream infections among spinal cord injury patients and impact of multidrug-resistant organisms.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Our study aimed to describe the outcome of bloodstream infection (BSI) in spinal cord injury (SCI) patients and their associated risk factors for severity and mortality. SETTING: A French University Hospital. METHODS: We conducted a retrospective cohort study of all BSIs occurring in hospitalized SCI patients. We analyzed their outcome and risk factors especially the impact of multidrug-resistant organisms (MDROs). RESULTS: Overall, 318 BSIs occurring among 256 patients were included in the analysis. Mean age was 50.8 years and gender ratio (M/F) was 2.70, with a mean injury duration of 11.6 years.Severity and 30-day mortality of BSI episodes were, respectively, 43.4% and 7.9%. BSI severity was significantly more frequent when caused by respiratory tract infections (RTIs) (odds ratio (OR)=1.38; 95% confidence interval (CI): 1.13-1.44) and significantly lower when caused by urinary tract infections (UTIs) (OR=0.47; 95% CI: 0.28-0.76). BSI mortality was significantly higher when caused by RTIs (OR=3.08; 95% CI: 1.05-8.99), catheter-related bloodstream infections (OR=3.54; 95% CI: 1.36-9.18) or Pseudomonas aeruginosa infections (OR=3.79; 95% CI: 1.14-12.55).MDROs were responsible for 41.2% of all BSI. They have no impact on severity and mortality, whichever be the primary site of infection.In multivariate analysis, mortality was higher when BSI episodes were due to RTIs (OR=3.26; 95% CI: 1.29-8.22) and Pseudomonas aeruginosa infections (OR=3.53; 95% CI: 1.06-11.70), or when associated with immunosuppressive therapy (OR=2.57; 95% CI: 1.14-5.78) or initial severity signs (OR=1.68; 95% CI: 1.01-2.81). CONCLUSION: BSI occurring in SCI population were often severe but mortality remained low. MDROs were frequent but not associated with severity or mortality of BSI episodes. Risk factors associated with mortality were initial severe presentation, RTI, immunosuppressive therapy and BSI due to Pseudomonas aeruginosa.

Serum protein electrophoresis: an interesting diagnosis tool to distinguish viral from bacterial community-acquired pneumonia.

29-69 % of pneumonias are microbiologically documented because it can be considered as an invasive procedure with variable test sensitivity. However, it drastically impacts therapeutic strategy in particular the use of antibiotics. Serum protein electrophoresis (SPEP) is a routine and non-invasive test commonly used to identify serum protein disorders. As virus and bacteria may induce different globulins production, we hypothesize that SPEP can be used as an etiological diagnosis test. Retrospective study conducted from 1/1/13 until 5/1/15 among patient hospitalized for an acute community-acquired pneumonia based on fever, crackles and radiological abnormalities. α/ß, α/γ, ß/γ globulins and albumin/globulin (A/G) ratio were calculated from SPEP. Data were analyzed in 3 groups: documented viral (DVP) or bacterial pneumonia (DBP) and supposedly bacterial pneumonia (SBP). We used ANOVA statistic test with multiple comparisons using CI95 and ROC curve to compare them. 109 patients included divided into DBP (n = 16), DVP (n = 26) and SBP (n = 67). Mean age was 62 ± 18 year-old with a sex ratio M/F of 1.3. Underlying conditions (e.g. COPD, diabetes) were comparable between groups in multivariate analysis. Means of A/G ratio were 0.80 [0.76-0.84], 0.96 [0.91-1.01], 1.08 [0.99-1.16] respectively for DBP, SBP and DVP (p = 0.0002). A/G ratio cut-off value of 0.845 has a sensitivity of 87.5 % and a specificity of 73.1 %. A/G ratio seems to be an easy diagnostic tool to differentiate bacterial from viral pneumonia. A/G ratio cut-off value below 0.845 seems to be predictable of a bacterial origin and support the use of antibiotics.

Blood stream infections due to multidrug-resistant organisms among spinal cord-injured patients, epidemiology over 16 years and associated risks: a comparative study.

STUDY DESIGN: Retrospective study. OBJECTIVES: We aimed to describe the epidemiology of multidrug-resistant organisms (MDROs) during bloodstream infection (BSI) and identify associated risks of MDROs among patients with spinal cord injury (SCI). SETTING: A teaching hospital, expert center in disability, in France. METHODS: We studied a retrospective cohort of all BSIs occurring in SCI patients hospitalized over 16 years. We described the prevalence of MDRO BSI among this population and its evolution over time and compared the BSI population due to MDROs and due to non-MDROs. RESULTS: A total of 318 BSIs occurring among 256 patients were included in the analysis. The most frequent primary sites of infection were urinary tract infection (34.0%), pressure sore (25.2%) and catheter line-associated bloodstream infection (11.3%). MDROs were responsible for 41.8% of BSIs, and this prevalence was stable over 16 years. No significant associated factor for MDRO BSI could be identified concerning sociodemographic and clinical characteristics, primary site of infection and bacterial species in univariate and multivariate analyses. BSI involving MDROs was not associated with initial severity of sepsis compared with infection without MDROs (43.8 vs 43.6%, respectively) and was not associated either with 30th-day mortality (6.2 vs 9%, respectively). CONCLUSION: During BSI occurrence in an SCI population, MDROs are frequent but remain stable over years. No associated risk can be identified that would help optimize antibiotic treatment. Neither the severity of the episode nor the mortality is significantly different when an MDRO is involved.

[Early post-exposure and curative therapeutic strategies against COVID-19]. / Covid-19 : mise à jour des stratégies thérapeutiques curatives précoces et du patient sous oxygénothérapie.

INTRODUCTION: There now exist preventive and curative treatments available for both early and advanced stages of COVID-19 management. CURRENT KNOWLEDGE: Antibiotics have no place in the initial therapeutic management of Sars-Cov-2 pneumonia. On the other hand, corticosteroids are recommended for patients requiring oxygen therapy≥2L/min. According to the latest recommendations, nirmatrelvir/ritonavir is indicated as an early treatment for adults not requiring oxygen therapy but at high risk of developing a severe form of COVID-19. In case of contraindication, remdesivir is an alternative therapy. PERSPECTIVES: Although there is no indication for convalescent plasma outside of clinical trials, it seems promising for immunocompromised patients, particularly those with B lymphopenia. It is noteworthy that currently, with the predominance of the Omicron XBB.1.5 variant, monoclonal antibodies are no longer recommended as therapy except for sotrovimab, which still has partial efficacy and could be considered after expert opinion as salvage therapy in a previously well-established program. CONCLUSION: Despite the evolution of variants, antivirals still appear to have activity and remain the first-line treatment for patients, in addition to vaccination.

Comparison of six generic vancomycin products for treatment of methicillin-resistant Staphylococcus aureus experimental endocarditis in rabbits.

Concerns have recently emerged about the potency and the quality of generic vancomycin (VAN) products approved for use in humans, based on experiments in a neutropenic mouse thigh infection model. However, other animal models may be more appropriate to decipher the bactericidal activities of VAN generics in vivo and to predict their efficacy in humans. We aimed to compare the bactericidal activities of six generic VAN products currently used in France (Mylan and Sandoz), Spain (Hospira), Switzerland (Teva), and the United States (Akorn-Strides and American Pharmaceutical Products [APP]) in a rabbit model of aortic valve endocarditis induced by 8 × 10(7) CFU of methicillin-resistant Staphylococcus aureus (MRSA) strain COL (VAN MIC, 1.5 µg/ml). In vitro, there were no significant differences in the time-kill curve studies performed with the six generic VAN products. Ten rabbits in each group were treated with intravenous (i.v.) VAN, 60 mg/kg of body weight twice a day (b.i.d.) for 4 days. Mean peak serum VAN levels, measured 45 min after the last injection, ranged from 35.5 (APP) to 45.9 µg/ml (Teva). Mean trough serum VAN levels, measured 12 h after the last injection, ranged from 2.3 (Hospira) to 9.2 (APP) µg/ml. All generic VAN products were superior to controls (no treatment) in terms of residual organisms in vegetations (P < 0.02 for each comparison) and in the spleen (P < 0.005 for each comparison). Pairwise comparisons of generic VAN products found no significant differences. In conclusion, a stringent MRSA endocarditis model found no significant differences in the bactericidal activities of six generic VAN products currently used in Europe and America.

Effect of achieving bone sterilisation on bone architecture and bone marrow, in an experimental rabbit model of osteomyelitis caused by carbapenemase-producing Enterobacterales.

OBJECTIVES: Natural history and treatment of bone infections caused by carbapenemase-producing Enterobacterales (CPE) are poorly defined. We evaluated the effect of treatment on the progression of subacute osteomyelitis in a rabbit model. METHODS: Two isolates were used: a KPC-producing Klebsiella pneumoniae and an Escherichia coli harbouring blaOXA-48 and blaCTX-M15 inserts, both susceptible to gentamicin, colistin, fosfomycin, and ceftazidime-avibactam. Osteomyelitis was induced in rabbits by tibial injection of 2 × 108 colony-forming units/mL. Antibiotics were started 14 d later, for 7 d, in 6 groups of 12 rabbits. Three days after treatment completion (D24), rabbits were euthanised and bones were cultured. Bone marrow and bone architecture macroscopic changes were evaluated through analysis of pictures by investigators unaware of the rabbit treatment group and microbiological outcome, using scales ranging from 0 (normal) to 3 (severe lesions) depending on modifications. RESULTS: Bone marrow modifications induced by local infection were similar between prematurely deceased animals and non-sterilised animals (P = 0.14) but differed significantly from animals that achieved bone sterilisation after treatment (P = 0.04). Conversely, when comparing bone deformity, rabbits who died early (n = 13) had similar bone architecture as those achieving bone sterilisation (P = 0.12), as opposed to those not sterilised after treatment (P = 0.04). After a multivariate logistic regression, bone marrow scale ≤2 was associated with bone sterilisation (P < 0.001), and bone architecture scale ≤2 was associated with bone sterilisation (adjusted odds ratio = 2.7; 95% confidence interval 1.14-6.37) and KPC infection (adjusted odds ratio = 5.1; 95% confidence interval 2.17-12.13). CONCLUSION: Effective antibacterial treatment reduces bone architecture distortion and bone marrow changes. These variables may be used as proxy for bone sterilisation.

Hip Joint Infections Caused by Multidrug-Resistant Enterobacterales Among Patients With Spinal Cord Injury: Experience of a Reference Center in the Greater Paris Area.

Background: We aimed to describe the management and treatment of hip joint infections caused by multidrug-resistant Enterobacterales among patients with spinal cord injury (SCI). Methods: We included all hip joint infections associated with grade IV decubitus ulcers caused by extended-spectrum beta-lactamase producing Enterobacterales (ESBL-PE) and carbapenemase-producing Enterobacterales treated in a reference center for bone and joint infections over 9 years in a retrospective study. Results: Seventeen SCI patients with ischial pressure ulcers breaching the hip capsule (mean age 52 ± 15 years) were analyzed. In 16 patients, paraplegia was secondary to trauma and 1 was secondary to multiple sclerosis. Infections were mostly polymicrobial (n = 15; 88.2%), notably caused by Klebsiella pneumoniae (n = 10) and Staphylococcus aureus (n = 10). The carbapenemases identified were exclusively OXA-48-type (n = 3) including 2 isolates coexpressed with ESBL-PE within the same bacterial host. Multidrug-resistant Enterobacterales were commonly resistant to fluoroquinolones (n = 12; 70.6%). Most therapies were based on carbapenems (n = 10) and combination therapies (n = 13). Median duration of treatment was 45 (6-60) days. Of 17 cases of hip joint infections, 94.1% (n = 16) benefited from a femoral head and neck resection. Infection control was initially achieved in 58.8% (n = 10) of cases and up to 88.2% after revision surgeries, after a median follow-up of 3 (1-36) months. Conclusions: Hip infections among SCI patients caused by multidrug-resistant Enterobacterales are often polymicrobial and fluoroquinolones-resistant infections caused by Klebsiella pneumoniae and S aureus, highlighting the need for expert centers with pluridisciplinary meetings associating experienced surgeons, clinical microbiologists, and infectious disease specialists.

Native bone and joint infections caused by extended-spectrum ß-lactamase-producing Enterobacterales: experience of a reference centre in the Greater Paris area.

Antibiotic treatment of native osteomyelitis caused by extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) is a challenge. Limited epidemiological and outcome data are available. This retrospective cohort study included osteomyelitis patients with ESBL-PE infections treated in a reference centre for bone and joint infections (BJIs) between 2011-2019. Twenty-nine patients with native BJI (mean age, 44.4 ± 15.7 years) were analysed. Fifteen cases were paraplegic patients with ischial pressure sores breaching the hip capsule. Other cases included eight other hip infections, four tibial infections and two foot infections. Infections were mostly polymicrobial (n = 23; 79.3%), including Staphylococcus aureus (n = 13; 8 methicillin-resistant). Klebsiella pneumoniae (n = 13) was the most frequent ESBL-producing species identified, followed by Escherichia coli (n = 10), including 3 E. coli/K. pneumoniae co-infections, and Enterobacter spp. (n = 9). ESBL-PE were rarely susceptible to fluoroquinolones (n = 4; 13.8%). Most therapies were based on carbapenems (n = 22) and combination therapies (n = 19). The median duration of treatment was 41 (5-60) days. Primary control of the infection was achieved in 62.1% (18/29) of cases and up to 86.2% after second look surgeries, after a median follow-up of 6 (1-36) months. Infection with ESBL-producing K. pneumoniae was associated with failure (P = 0.001), whereas age, infection location, prior colonisation and antimicrobial therapy were not found to be predictors of outcome. ESBL-PE native BJIs are often polymicrobial and fluoroquinolone-resistant infections caused by K. pneumoniae, highlighting the need for expert centres with pluridisciplinary meetings with experienced surgeons.

[Cardiovascular disorders in patients infected with 2019 novel coronavirus]. / Atteintes du système cardiovasculaire chez les patients atteints de maladie à coronavirus 19.

The coronavirus disease 2019 (COVID-19) outbreak has become a worldwide public health concern. Cardiovascular complications are relatively frequent, reaching 20% of COVID-19 patients and 43% of COVID-19 patients admitted in Intensive Care Unit. Cardiac injury mechanisms are multiple, including hyperinflammation, pro-coagulant and pro-thrombotic states, sepsis related cardiomyopathy, hypoxia in relation with lung severity, hemodynamic instability, cytokine storm, critically illness, direct myocardial insult by acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and stress cardiomyopathy. The authors report a narrative review about cardio-vascular complications and predictive factors of mortality in patients infected with COVID-19.

Successful treatment of meningococcal bacteremia using oral doxycycline: A case report.

We report the case of an 18-year-old immunocompetent man who presented to the hospital with fever, headaches, and arthromyalgia, which progressed to include an erythematous rash. He had a history of a tick bite 72 h earlier. The diagnosis of rickettsial infection was suspected and a course of doxycycline was initiated for a total of 5 days. His evolution was rapidly favorable under treatment, with resolution of the symptoms within 24 h. Blood cultures came back positive for Neisseria meningitidis serotype B, indicating an authentic purpura fulminans. Purpura fulminans is a medical emergency, a syndrome of intravascular thrombosis characterized by a very rapid evolution that requires early recognition and specific treatment. It is commonly described in the young and healthy patient and has high mortality and morbidity. Common bacteria mainly associated with purpura fulminans are Meningococcus spp., Pneumococcus spp., and Staphylococcus spp.

Case series of carbapenemase-producing Enterobacteriaceae osteomyelitis: Feel it in your bones.

OBJECTIVES: Limited data have been reported regarding osteomyelitis due to carbapenemase-producing Enterobacteriaceae (CPE), including co-infections with extended-spectrum ß-lactamase (ESBL)-producing micro-organisms. METHODS: We conducted a retrospective study in a reference centre for bone and joint infections from 2011 to 2019 among patients infected with CPE. RESULTS: Nine patients (mean age 46.8 ± 16.6 years), including three with infected implants, were identified. Infections were mostly polymicrobial (n = 8/9), including Staphylococcus aureus (n = 6/9). CPE were mainly OXA-48-type, associated with ESBL-producing Enterobacteriaceae (n = 8/9), of which 5/9 isolates were Klebsiella pneumoniae. Control of the infection was achieved in seven cases. CONCLUSIONS: CPE osteomyelitides are essentially polymicrobial and fluoroquinolone-resistant infections, highlighting the need for efficient surgery with implant removal.

Urinary tract infections in patients with neurogenic bladder.

Urinary tract infections (UTIs) in patients with neurogenic bladder are a major public health issue due to their high incidence and major consequences. Despite their frequency and potential severity, their physiopathology and management are poorly known. We provide a narrative literature review on the epidemiology, physiopathology, diagnostic criteria, microbiology, antimicrobial management, and prevention. UTIs among patients with neurogenic bladder are associated with high morbidity and healthcare utilization. Risk factors for UTI among this population are: indwelling catheter, urinary stasis, high bladder pressure, and bladder stones. Their diagnosis is a major challenge as clinical signs are often non-specific and rare. A urinary sample should be analyzed in appropriate conditions before any antibiotic prescription. According to most guidelines, a bacterial threshold≥103CFU/ml associated with symptoms is acceptable to define UTI in patients with neurogenic bladder. The management of acute symptomatic UTI is not evidence-based. A management with a single agent and a short antibiotic treatment of 10 days or less seems effective. Antibiotic selection should be based on the patient's resistance patterns. Asymptomatic bacteriuria should not be treated to avoid the emergence of bacterial resistance. Regarding preventive measures, use of clean intermittent catheterization, intravesical botulinum toxin injection, and prevention using antibiotic cycling are effective. Bacterial interference is promising but randomized controlled trials are needed. Large ongoing cohorts and randomized controlled trials should soon provide more evidence-based data.

Management of established pressure ulcer infections in spinal cord injury patients.

OBJECTIVES: Pressure ulcers are frequently observed in spinal cord injury (SCI) patients. They can be life-threatening and are a major medico-economic burden. Despite their frequency, their pathophysiology and optimal management are still poorly understood. Most available data comes from non-comparative studies, especially in terms of antimicrobial use. METHODS: We performed a critical review of the literature and opinions of infectious disease specialists based in a French expert center for this disease. We mainly focused on antimicrobial treatments prescribed in this situation. RESULTS: These infections are usually clinically diagnosed. Microbiological samples are not the gold standard for this assessment. Furthermore, reliable microbiological identification is a major challenge but should help select antimicrobial treatment. Imaging technique could be helpful but cannot replace the physical examination. The choice of antimicrobials must consider the potential ecological collateral damages in this vulnerable population. Antimicrobial therapy should be as short as possible, adapted to the microbiological identification, and must have suitable bioavailability. CONCLUSION: Management of infected pressure ulcers is a major concern in disabled patients already highly exposed to antimicrobial treatment and multidrug-resistant organisms colonization. Extensive data is required.

Fecal microbiota transplantation to eradicate vancomycin-resistant enterococci colonization in case of an outbreak.

OBJECTIVE: A rapid and worrying emergence of vancomycin-resistant enterococci (VRE) gut colonization is occurring worldwide and may be responsible for outbreaks, especially in healthcare facilities. While no efficient decolonization strategies are recommended, we assessed fecal microbiota transplantation (FMT) to eradicate VRE colonization. PATIENTS AND METHOD: Our main objective was to measure the impact of FMT on decolonization of VRE carriers, confirmed by at least two consecutive negative rectal swabs at one-week interval during a 3-month follow-up period. Patients received no antibiotic prior to the FMT. RESULTS: After a month only three patients remained colonized with VRE. Decolonization was associated with 87.5% (n=7) of success after three months as only one patient remained colonized. CONCLUSION: Our first results confirm that the FMT seems to be safe, with an impact on VRE colonization over time that may help control outbreaks.