Breakthrough Clostridium difficile Infection in Cirrhotic Patients Receiving Rifaximin.

Background: Patients with cirrhosis are at high risk of Clostridium difficile infection (CDI). Rifaximin is commonly used in cirrhotic patients as prophylaxis for hepatic encephalopathy (HE). Several studies have demonstrated the efficacy of rifaximin in the treatment of CDI; however, resistance to rifaximin has also been reported. Few studies have assessed the risk of developing CDI in cirrhotic patients receiving rifaximin. Our objective was to assess the incidence and characteristics of CDI in patients with cirrhosis, especially in those who received rifaximin. Methods: We assessed the incidence and clinical characteristics of CDI in cirrhotic patients over a 6-year period in our hospital. Medical charts were retrospectively reviewed. Ribotyping and antimicrobial susceptibility testing of all strains against rifaximin were performed. Results: A total of 388 cirrhotic patients were included, of whom 127 patients had at least 1 episode of diarrhea in which a sample was sent to the laboratory. CDI was detected in 46 patients. Fourteen patients (30.4%) were receiving rifaximin as prophylaxis for HE. The main ribotypes detected were 001 (30.4%), followed by 014 (19.6%). Resistance to rifaximin was 34.1% overall, and 84.6% in patients who had received rifaximin. Multivariate analysis showed that rifamycin therapy and ribotype 001 were significant risk factors for having a rifaximin-resistant C. difficile strain. Conclusions: A high percentage of CDI cases were detected in cirrhotic patients receiving rifaximin, mostly owing to selection of rifaximin-resistant C. difficile strains. Clinicians should be aware of the risk of CDI in cirrhotic patients, even in those receiving rifaximin.

Tracking Nosocomial Klebsiella pneumoniae Infections and Outbreaks by Whole-Genome Analysis: Small-Scale Italian Scenario within a Single Hospital.

Multidrug-resistant (MDR) Klebsiella pneumoniae is one of the most important causes of nosocomial infections worldwide. After the spread of strains resistant to beta-lactams at the end of the previous century, the diffusion of isolates resistant to carbapenems and colistin is now reducing treatment options and the containment of infections. Carbapenem-resistant K. pneumoniae strains have spread rapidly among Italian hospitals, with four subclades of pandemic clonal group 258 (CG258). Here we show that a single Italian hospital has been invaded by three of these subclades within 27 months, thus replicating on a small scale the "Italian scenario." We identified a single clone responsible for an epidemic outbreak involving seven patients, and we reconstructed its star-like pattern of diffusion within the intensive care unit. This epidemiological picture was obtained through phylogenomic analysis of 16 carbapenem-resistant K. pneumoniae isolates collected in the hospital during a 27-month period, which were added to a database of 319 genomes representing the available global diversity of K. pneumoniae strains. Phenotypic and molecular assays did not reveal virulence or resistance determinants specific for the outbreak isolates. Other factors, rather than selective advantages, might have caused the outbreak. Finally, analyses allowed us to identify a major subclade of CG258 composed of strains bearing the yersiniabactin virulence factor. Our work demonstrates how the use of combined phenotypic, molecular, and whole-genome sequencing techniques can help to identify quickly and to characterize accurately the spread of MDR pathogens.

Fast track SSTI management program based on a rapid molecular test (GeneXpert® MRSA/SA SSTI) and antimicrobial stewardship.

PURPOSE: This study examines the impacts of a skin and soft tissue infection (SSTI) management program involving a rapid diagnostic algorithm (Gram stain plus real-time PCR, GeneXpert® MRSA/SA SSTI) performed directly on clinical samples plus antimicrobial stewardship (AMS) counseling of the responsible physician. METHODS: Participants were 155 consecutive adult inpatients with SSTI and good quality clinical samples submitted to the microbiology laboratory from April 2016 to January 2017. Results of the rapid test and AMS recommendations were phoned through to the responsible physician. The comparison group was a historical cohort. RESULTS: Most SSTI were surgical wound infections (41.3% vs 38.1% for the intervention and comparison groups respectively) followed by diabetic foot (14.2% and 18.1%), abscesses (13.5% both) and cellulitis (12.9% both). Isolated microorganisms were mostly Gram-negative bacilli (two-thirds), followed by Staphylococcus aureus (SA). The ratio methicillin-susceptible SA (MSSA) to methicillin-resistant SA (MRSA) was 4:1. Improvements in the intervention cohort were: DOT (22.0 vs. 24.3 days, p = 0.007), treatment duration per SSTI episode (14.1 vs. 15.0 days, p = 0.072), treatment cost (433.1 vs. 533.3 €, p = 0.039), length of stay (18.6 vs 20.7 days, p = 0.031), related mortality (1 vs. 4 patients, p = 0.022) and Clostridium difficile infection (CDI) (4 vs. 8 patients, p = 0.050). In 48 cases (31.4%) in the intervention group, advice was given to improve empiric antibiotic treatment. CONCLUSION: This type of program could help adjust antibiotic treatment when inappropriate, reducing antibiotic use and costs, length of stay, CDI and related mortality.

Three different patterns of positive Clostridium difficile laboratory tests. A comparison of clinical behavior.

Clostridium difficile (CD) diagnosis is very varied and under discussion. Different research groups disagree on the clinical significance of patients with negative direct toxin and positive polymerase chain reaction (PCR) or even more with direct toxin and glutamate dehydrogenase (GDH) both negatives, but CD detected by toxigenic culture (TC). The objective was to analyze the characteristics of patients with 3 different diagnostic criteria. We compared these 3 groups of patients: group 1: (GDH+/direct toxin+/PCR+), group 2: (GDH+/direct toxin-/PCR+) and group 3: (GDH-/direct toxin-/PCR not done/TC+). The proportion of patients with CD infection (CDI) (not colonization) for groups 1 to 3 was, respectively, 90.3%, 95.4%, and 59.1%. No differences between severity (40.8%, 38.5%, 27.3%), recurrence (20.3%, 24.1%, 7.6%), or related mortality (12.5%, 5.2%, 0%) were found within the 3 groups of patients. Laboratory clinical results should not be used as the only tool to differentiate CDI versus colonization or severity. We recommend that PCR or a second-look TC be performed on all patients.

Gradient diffusion antibiogram used directly on bronchial aspirates for a rapid diagnosis of ventilator-associated pneumonia.

Background: In patients with suspected ventilator-associated pneumonia, a rapid etiological diagnosis is crucial as incorrect or delayed treatment in the first few hours leads to a worse prognosis and a higher mortality rate. This study examines the efficacy of a rapid antibiogram on bronchial aspirates in patients with suspected ventilator-associated pneumonia (VAP). Methods: The direct gradient diffusion susceptibility testing method (GDM) on respiratory samples was compared with a standard broth microdilution method (BMD) after quantitative cultures in patients with suspicion of VAP. Samples were preselected by Gram staining (for good quality microbiological samples with a predominant single bacterial morphotype). The antibiotics tested were ceftazidime, ceftobiprole, ceftolozane-tazobactam, meropenem, doripenem, and tedizolid. Results: Over a 16-month study period, 445 bronchial aspirate samples were selected from 1376 samples received at our laboratory from 672 adult patients. By direct plating on Mueller-Hinton agar, we recovered 504 (95.5%) of the 528 microorganisms identified by the standard semiquantitative method. Antimicrobial susceptibility testing by GDM was compared with the BMD method in 472 strains (216 Enterobacteriaceae, 138 P. aeruginosa and 118 S. aureus.) and 1652 individual microorganism-antimicrobial agent combinations. There was total agreement between both methods in 98% of combinations. The Kappa index between both techniques was excellent (over 80%). There was only one potential major error for P. aeruginosa susceptibility to ceftazidime. Conclusions: The six GDM strips directly placed on plated bronchial aspirates obtained from patients with a suspicion of VAP provided accurate and reliable susceptibility results within 24 h.