Effectiveness and safety of cefazolin versus cloxacillin in endocarditis due to methicillin-susceptible Staphylococcus spp.: a multicenter propensity weighted cohort study.

PURPOSE: To compare the effectiveness and safety of cefazolin versus cloxacillin for the treatment of infective endocarditis (IE) due to methicillin-sensitive Staphylococci (MSS). METHODS: Data were retrospectively collected on patients treated for a definite MSS endocarditis who received cefazolin or cloxacillin for at least 10 consecutive days in six French hospitals between January-1 2014 and December-31 2020. The primary endpoint was treatment failure defined as a composite of death within 90 days of starting antibiotherapy, or embolic event during antibiotherapy, or relapse of IE within 90 days of stopping antibiotherapy. We used Cox regression adjusted for the inverse probability of treatment weighting of receiving cefazolin. RESULTS: 192 patients were included (median age 67.8 years). IE was caused by S.aureus in 175 (91.1%) and by coagulase-negative staphylococci in 17 (8.9%). Ninety-four patients (48.9%) received cefazolin, and 98 (51%) received cloxacillin. 34 patients (34.7%) with cefazolin and 26 (27.7%) with cloxacillin met the composite primary endpoint, with no significant differences between groups (adjusted HR = 1.13, 95% CI 0.63 to 2.03). There were no significant differences in secondary efficacy endpoints or biological safety events. CONCLUSION: The effectiveness of cefazolin did not significantly differ from cloxacillin for the treatment of MSS endocarditis.

Temocillin versus carbapenems for urinary tract infection due to ESBL-producing Enterobacteriaceae: a multicenter matched case-control study.

OBJECTIVES: To compare the efficacy of temocillin with carbapenems for extended spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae urinary tract infections (ESBL-E UTI). METHODS: A multicenter retrospective case-control study of adults with ESBL-E UTI was conducted between January 2015 and October 2019. Cases received temocillin ≥ 50% of the effective antibiotic therapy duration and controls exclusively received carbapenem; they were statistically matched (1:1 ratio) on 6-month period, sex and age. The clinical cure at the end of antibiotic therapy was analysed using conditional logistic regression. RESULTS: Seventy-two temocillin cases were matched to 72 carbapenem controls. Most (67%) were male, median age was 69.4 years, 81 (56%) were immunocompromised, including 44 (31%) solid organ transplant recipients. There was no difference between cases and controls for baseline characteristics and microorganisms involved: Klebsiella pneumoniae in 59 (41%), Escherichia coli in 57 (40%), and Enterobacter spp. in 24 (17%). The median time from admission to effective antibiotic therapy was 0 days [range, 0-2]. Among cases, first-line antibiotic therapy (≤ 72 hours) was temocillin in six (8%) and carbapenems in 39 (54%). Temocillin was given at the median daily dose of 4 g [range, 2-4] after 3 days [range, 2-5] of carbapenems. Patients received temocillin for 81% [range, 70-93] of the effective antibiotic course duration over 11 days [range, 8-14]. The effective antibiotic duration was similar in cases and controls (P = 0.067). Clinical cure at the end of antibiotic therapy was 94% (68/72) in cases vs. 99% (71/72) in controls (P = 0.206), with no difference among immunocompromised and solid organ transplant patients (P > 0.050). CONCLUSIONS: Temocillin effectively relayed ß-lactams, including carbapenems, to treat (complicated) ESBL-E UTI. Its efficacy was consistent among kidney transplant recipients.

Clinical Cutaneous Features of Patients Infected With SARS-CoV-2 Hospitalized for Pneumonia: A Cross-sectional Study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a current pandemic worldwide. This virus can reach all organs and disturbs the immune system, leading to a cytokine storm in severe forms. We aimed to report cutaneous features among coronavirus disease 2019 (COVID-19) hospitalized patients. METHODS: We performed a cross-sectional study on 1 given day among all patients hospitalized in acute care for COVID-19 and included all patients with cutaneous features. Follow-up 48 hours later was obtained. RESULTS: Among 59 adult patients hospitalized on the day of the study in an infectious diseases ward for SARS-CoV-2 infection who were confirmed by molecular assay and/or radiological findings (computed tomography scan), 40 were included. Several cutaneous manifestations were found: macular exanthema (80%), face edema (32%), livedo (13%), urticarial rash (8%), purpura (5%), oral lichenoid lesions (33%), and conjunctivitis (18%). Cutaneous biopsy was performed in 17 patients. Histological findings showed mast cell hyperplasia (100%), superficial perivascular infiltrate of lymphocytes (94%), and superficial edema (47%) consistent with capillary leak. CONCLUSIONS: Various dermatological signs can be encountered during COVID-19. A macular rash was the most frequent. All cutaneous features could be related to a vascular leak process.

The diagnostic utility of the "Thwaites' system" and "lancet consensus scoring system" in tuberculous vs. non-tuberculous subacute and chronic meningitis: multicenter analysis of 395 adult patients.

BACKGROUND: Tuberculous meningitis (TBM) represents a diagnostic and management challenge to clinicians. The "Thwaites' system" and "Lancet consensus scoring system" are utilized to differentiate TBM from bacterial meningitis but their utility in subacute and chronic meningitis where TBM is an important consideration is unknown. METHODS: A multicenter retrospective study of adults with subacute and chronic meningitis, defined by symptoms greater than 5 days and less than 30 days for subacute meningitis (SAM) and greater than 30 days for chronic meningitis (CM). The "Thwaites' system" and "Lancet consensus scoring system" scores and the diagnostic accuracy by sensitivity, specificity, and area under the curve of receiver operating curve (AUC-ROC) were calculated. The "Thwaites' system" and "Lancet consensus scoring system" suggest a high probability of TBM with scores ≤4, and with scores of ≥12, respectively. RESULTS: A total of 395 patients were identified; 313 (79.2%) had subacute and 82 (20.8%) with chronic meningitis. Patients with chronic meningitis were more likely caused by tuberculosis and had higher rates of HIV infection (P < 0.001). A total of 162 patients with TBM and 233 patients with non-TBM had unknown (140, 60.1%), fungal (41, 17.6%), viral (29, 12.4%), miscellaneous (16, 6.7%), and bacterial (7, 3.0%) etiologies. TMB patients were older and presented with lower Glasgow coma scores, lower CSF glucose and higher CSF protein (P < 0.001). Both criteria were able to distinguish TBM from bacterial meningitis; only the Lancet score was able to differentiate TBM from fungal, viral, and unknown etiologies even though significant overlap occurred between the etiologies (P < .001). Both criteria showed poor diagnostic accuracy to distinguish TBM from non-TBM etiologies (AUC-ROC was <. 5), but Lancet consensus scoring system was fair in diagnosing TBM (AUC-ROC was .738), sensitivity of 50%, and specificity of 89.3%. CONCLUSION: Both criteria can be helpful in distinguishing TBM from bacterial meningitis, but only the Lancet consensus scoring system can help differentiate TBM from meningitis caused by fungal, viral and unknown etiologies even though significant overlap occurs and the overall diagnostic accuracy of both criteria were either poor or fair.

Compassionate Use of Cefiderocol to Treat a Case of Prosthetic Joint Infection Due to Extensively Drug-Resistant Enterobacter hormaechei.

We report the case of a 67-year old man with a right knee prosthetic joint infection due to extensively drug-resistant Enterobacter hormaechei. The resistance phenotype was due to the overproduction of the intrinsic cephalosporinase (ACT-5) associated with the production of three acquired ß-lactamases (CTX-M-15, TEM-1B and OXA-1), and a putative membrane decreased permeability. He was first treated with colistin-tigecyclin due to adverse drug reactions; treatment was switched to cefiderocol for a 12-week antibiotic duration, with a favorable outcome.

Clinicopathological profile of gastrointestinal tuberculosis: a multinational ID-IRI study.

Data are relatively scarce on gastro-intestinal tuberculosis (GITB). Most studies are old and from single centers, or did not include immunosuppressed patients. Thus, we aimed to determine the clinical, radiological, and laboratory profiles of GITB. We included adults with proven GITB treated between 2000 and 2018. Patients were enrolled from 21 referral centers in 8 countries (Belgium, Egypt, France, Italy, Kazakhstan, Saudi Arabia, UK, and Turkey). One hundred four patients were included. Terminal ileum (n = 46, 44.2%), small intestines except terminal ileum (n = 36, 34.6%), colon (n = 29, 27.8%), stomach (n = 6, 5.7%), and perianal (one patient) were the sites of GITB. One-third of all patients were immunosuppressed. Sixteen patients had diabetes, 8 had chronic renal failure, 5 were HIV positive, 4 had liver cirrhosis, and 3 had malignancies. Intestinal biopsy samples were cultured in 75 cases (78.1%) and TB was isolated in 65 patients (86.6%). PCR were performed to 37 (35.6%) biopsy samples and of these, 35 (94.6%) were positive. Ascites samples were cultured in 19 patients and M. tuberculosis was isolated in 11 (57.9%). Upper gastrointestinal endoscopy was performed to 40 patients (38.5%) and colonoscopy in 74 (71.1%). Surgical interventions were frequently the source of diagnostic samples (25 laparoscopy/20 laparotomy, n = 45, 43.3%). Patients were treated with standard and second-line anti-TB medications. Ultimately, 4 (3.8%) patients died and 2 (1.9%) cases relapsed. There was a high incidence of underlying immunosuppression in GITB patients. A high degree of clinical suspicion is necessary to initiate appropriate and timely diagnostic procedures; many patients are first diagnosed at surgery.

Renal function markers and insulin sensitivity after 3 years in a healthy cohort, the EGIR-RISC study.

BACKGROUND: People with chronic renal disease are insulin resistant. We hypothesized that in a healthy population, baseline renal function is associated with insulin sensitivity three years later. METHODS: We studied 405 men and 528 women from the European Group for the study of Insulin Resistance - Relationship between Insulin Sensitivity and Cardiovascular disease cohort. Renal function was characterized by the estimated glomerular filtration rate (eGFR) and by the urinary albumin-creatinine ratio (UACR). At baseline only, insulin sensitivity was quantified using a hyperinsulinaemic-euglycaemic clamp; at baseline and three years, we used surrogate measures: the Matsuda insulin sensitivity index (ISI), the HOmeostasis Model Assessment of Insulin Sensitivity (HOMA-IS). Associations between renal function and insulin sensitivity were studied cross-sectionally and longitudinally. RESULTS: In men at baseline, no associations were seen with eGFR, but there was some evidence of a positive association with UACR. In women, all insulin sensitivity indices showed the same negative trend across eGFR classes, albeit not always statistically significant; for UACR, women with values above the limit of detection, had higher clamp measured insulin sensitivity than other women. After three years, in men only, ISI and HOMA-IS showed a U-shaped relation with baseline eGFR; women with eGFR> 105 ml/min/1.73m2 had a significantly higher insulin sensitivity than the reference group (eGFR: 90-105 ml/min/1.73m2). For both men and women, year-3 insulin sensitivity was higher in those with higher baseline UACR. All associations were attenuated after adjusting on significant covariates. CONCLUSIONS: There was no evidence to support our hypothesis that markers of poorer renal function are associated with declining insulin sensitivity in our healthy population.

Antituberculosis drug resistance patterns in adults with tuberculous meningitis: results of haydarpasa-iv study.

BACKGROUND: Tuberculous meningitis (TBM) caused by Mycobacterium tuberculosis resistant to antituberculosis drugs is an increasingly common clinical problem. This study aimed to evaluate drug resistance profiles of TBM isolates in adult patients in nine European countries involving 32 centers to provide insight into the empiric treatment of TBM. METHODS: Mycobacterium tuberculosis was cultured from the cerebrospinal fluid (CSF) of 142 patients and was tested for susceptibility to first-line antituberculosis drugs, streptomycin (SM), isoniazid (INH), rifampicin (RIF) and ethambutol (EMB). RESULTS: Twenty of 142 isolates (14.1 %) were resistant to at least one antituberculosis drug, and five (3.5 %) were resistant to at least INH and RIF, [multidrug resistant (MDR)]. The resistance rate was 12, 4.9, 4.2 and 3.5 % for INH, SM, EMB and RIF, respectively. The monoresistance rate was 6.3, 1.4 and 0.7 % for INH, SM and EMB respectively. There was no monoresistance to RIF. The mortality rate was 23.8 % in fully susceptible cases while it was 33.3 % for those exhibiting monoresistance to INH, and 40 % in cases with MDR-TBM. In compared to patients without resistance to any first-line drug, the relative risk of death for INH-monoresistance and MDR-TBM was 1.60 (95 % CI, 0.38-6.82) and 2.14 (95 % CI, 0:34-13:42), respectively. CONCLUSION: INH-resistance and MDR rates seemed not to be worrisome in our study. However, considering their adverse effects on treatment, rapid detection of resistance to at least INH and RIF would be most beneficial for designing anti-TB therapy. Still, empiric TBM treatment should be started immediately without waiting the drug susceptibility testing.

Tuberculous and brucellosis meningitis differential diagnosis.

BACKGROUND: The Thwaites and Lancet scoring systems have been used in the rapid diagnosis of tuberculous meningitis (TBM). However, brucellar meningoencephalitis (BME) has similar characteristics with TBM. The ultimate aim of this study is to infer data to see if BME should be included in the differential diagnosis of TBM when these two systems suggest the presence of TBM. METHOD: BME and TBM patients from 35 tertiary hospitals were included in this study. Overall 294 adult patients with BME and 190 patients with TBM were enrolled. All patients involved in the study had microbiological confirmation for either TBM or BME. Finally, the Thwaites and Lancet scoring systems were assessed in both groups. RESULTS: The Thwaites scoring system more frequently predicted BME cases (n = 292, 99.3%) compared to the TBM group (n = 182, 95.8%) (P = 0.017). According to the Lancet scoring system, the mean scores for BME and TBM were 9.43 ± 1.71 and 11.45 ± 3.01, respectively (P < 0.001). In addition, TBM cases were classified into "probable" category more significantly compared to BME cases, and BME cases were categorized into the "possible" category more frequently. CONCLUSIONS: When the Thwaites or Lancet scoring systems indicate TBM, brucellar etiology should also be taken into consideration particularly in endemic countries.

Hamsi scoring in the prediction of unfavorable outcomes from tuberculous meningitis: results of Haydarpasa-II study.

Predicting unfavorable outcome is of paramount importance in clinical decision making. Accordingly, we designed this multinational study, which provided the largest case series of tuberculous meningitis (TBM). 43 centers from 14 countries (Albania, Croatia, Denmark, Egypt, France, Hungary, Iraq, Italy, Macedonia, Romania, Serbia, Slovenia, Syria, Turkey) submitted data of microbiologically confirmed TBM patients hospitalized between 2000 and 2012. Unfavorable outcome was defined as survival with significant sequela or death. In developing our index, binary logistic regression models were constructed via 200 replicates of database by bootstrap resampling methodology. The final model was built according to the selection frequencies of variables. The severity scale included variables with arbitrary scores proportional to predictive powers of terms in the final model. The final model was internally validated by bootstrap resampling. A total of 507 patients' data were submitted among which 165 had unfavorable outcome. Eighty-six patients died while 119 had different neurological sequelae in 79 (16%) patients. The full model included 13 variables. Age, nausea, vomiting, altered consciousness, hydrocephalus, vasculitis, immunosuppression, diabetes mellitus and neurological deficit remained in the final model. Scores 1-3 were assigned to the variables in the severity scale, which included scores of 1-6. The distribution of mortality for the scores 1-6 was 3.4, 8.2, 20.6, 31, 30 and 40.1%, respectively. Altered consciousness, diabetes mellitus, immunosuppression, neurological deficits, hydrocephalus, and vasculitis predicted the unfavorable outcome in the scoring and the cumulative score provided a linear estimation of prognosis.