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Infections due to anaerobic bacteria can be severe and life-threatening. Susceptibility testing of anaerobes is not frequently performed in laboratories, but such testing is important to direct appropriate therapy. Anaerobic resistance is increasing globally, and resistance trends vary by geographic region. An overview of a variety of susceptibility testing methods for anaerobes is provided, and the advantages and disadvantages of each method are reviewed. Specific clinical situations warranting anaerobic susceptibility testing are discussed.

Background Currently, there is no agreed standard for exploring the antimicrobial activity of wound antiseptics in a phase 2/ step 2 test protocol. In the present study, a standardised in-vitro test is proposed, which allows to test potential antiseptics in a more realistically simulation of conditions found in wounds as in a suspension test. Furthermore, factors potentially influencing test results such as type of materials used as test carrier or various compositions of organic soil challenge were investigated in detail. Methods This proposed phase 2/ step 2 test method was modified on basis of the EN 14561 by drying the microbial test suspension on a metal carrier for 1 h, overlaying the test wound antiseptic, washing-off, neutralization, and dispersion at serial dilutions at the end of the required exposure time yielded reproducible, consistent test results. Results The difference between the rapid onset of the antiseptic effect of PVP-I and the delayed onset especially of polihexanide was apparent. Among surface-active antimicrobial compounds, octenidine was more effective than chlorhexidine digluconate and polihexanide, with some differences depending on the test organisms. However, octenidine and PVP-I were approximately equivalent in efficiency and microbial spectrum, while polihexanide required longer exposure times or higher concentrations for a comparable antimicrobial efficacy. Conclusion Overall, this method allowed testing and comparing differ liquid and gel based antimicrobial compounds in a standardised setting.

Background Rifaximin has demonstrated efficacy and safety for diarrhea-predominant irritable bowel syndrome (IBS-D). Aim To determine the rifaximin repeat treatment effect on fecal bacterial antibiotic susceptibility. Methods Patients with IBS in Trial 3 (TARGET 3) study who responded to open-label rifaximin 550 mg three times daily for 2 weeks, with symptom recurrence within 18 weeks, were randomized to double-blind treatment: two 2-week repeat courses of rifaximin or placebo, separated by 10 weeks. Prospective stool sample collection occurred before and after open-label rifaximin, before and after the first repeat course, and at the end of the study. Susceptibility testing was performed with 11 antibiotics, including rifaximin and rifampin, using broth microdilution or agar dilution methods. Results Of 103 patients receiving open-label rifaximin, 73 received double-blind rifaximin ( n  = 37) or placebo ( n  = 36). A total of 1429 bacterial and yeast isolates were identified, of which Bacteroidaceae (36.7%) and Enterobacteriaceae (33.9%) were the most common. In the double-blind phase, Clostridium difficile was highly susceptible to rifaximin [minimum inhibitory concentration (MIC) range 0.008–1 µg/mL] and rifampin (MIC range 0.004–0.25 µg/mL). Following double-blind rifaximin treatment, Staphylococcus isolates remained susceptible to rifaximin at all visits (MIC 50 range ≤0.06–32 µg/mL). Rifaximin exposure was not associated with long-term cross-resistance of Bacteroidaceae, Enterobacteriaceae, and Enterococcaceae to rifampin or nonrifamycin antibiotics tested. Conclusions In this study, short-term repeat treatment with rifaximin has no apparent long-term effect on stool microbial susceptibility to rifaximin, rifampin, and nonrifamycin antibiotics. ClinicalTrials.gov Identifier NCT01543178.

Background Recent reports have suggested the efficacy of a double carbapenem (DC) combination, including ertapenem, for the treatment of carbapenem-resistant Klebsiella pneumoniae (CR- Kp ) infections. We aimed to evaluate the clinical impact of such a regimen in critically ill patients. Methods This case–control (1:2), observational, two-center study involved critically ill adults with a microbiologically documented CR- Kp invasive infection treated with the DC regimen matched with those receiving a standard treatment (ST) (i.e., colistin, tigecycline, or gentamicin). Results The primary end point was 28-day mortality. Secondary outcomes were clinical cure, microbiological eradication, duration of mechanical ventilation and of vasopressors, and 90-day mortality. Forty-eight patients treated with DC were matched with 96 controls. Occurrence of septic shock at infection and high procalcitonin levels were significantly more frequent in patients receiving DC treatment ( p  < 0.01). The 28-day mortality was significantly higher in patients receiving ST compared with the DC group (47.9% vs 29.2%, p  = 0.04). Similarly, clinical cure and microbiological eradication were significantly higher when DC was used in patients infected with CR- Kp strains resistant to colistin (13/20 (65%) vs 10/32 (31.3%), p  = 0.03 and 11/19 (57.9%) vs 7/27 (25.9%), p  = 0.04, respectively). In the logistic regression and multivariate Cox-regression models, the DC regimen was associated with a reduction in 28-day mortality (OR 0.33, 95% CI 0.13–0.87 and OR 0.43, 95% CI 0.23–0.79, respectively). Conclusions Improved 28-day mortality was associated with the DC regimen compared with ST for severe CR- Kp infections. A randomized trial is needed to confirm these observational results. Trial registration ClinicalTrials.gov NCT03094494 . Registered 28 March 2017.

Antimicrobial resistance is a growing global health issue. It is also a recognised problem in veterinary medicine. Between September and December 2015 the authors administered a cross-sectional survey to licensed veterinarians in Washington State to assess factors affecting antimicrobial prescribing practices among veterinarians in Washington State. Two hundred and three veterinarians completed the survey. The majority of respondents (166, 82 per cent) were engaged in small animal or exotic animal practice. 24 per cent of respondents reported not ordering culture and sensitivity (C/S) testing in practice. Of the 76 per cent of veterinarians who reported ordering C/S tests, 36 per cent reported ordering such testing ‘often’ or ‘always’ when treating presumptive bacterial infections. Most respondents (65 per cent) mentioned cost as the most common barrier to ordering a C/S test. Only 16 (10 per cent) respondents reported having access to or utilising a clinic-specific antibiogram. This survey demonstrated that while antimicrobials are commonly used in veterinary practice, and veterinarians are concerned about antimicrobial resistance, cost is a barrier to obtaining C/S tests to guide antimicrobial therapy. Summaries of antimicrobial resistance patterns are rarely available to the practising veterinarian. Efforts to promote antimicrobial stewardship in a ‘One Health’ manner should address barriers to the judicious use of antimicrobials in the veterinary practice setting.

Background Nocardia species are ubiquitous in natural environments and can cause nocardiosis. In the present study, the use of Resazurin salt and Spectrophotometry were proposed as alternative methods to reduce subjectivity in the interpretation of susceptibility results to antimicrobials by the broth microdilution method for Nocardia spp. Results The susceptibility of Nocardia spp. isolates to Amikacin, Ciprofloxacin, Minocycline and Trimethoprim-Sulfamethoxazole was evaluated by Minimum Inhibitory Concentration (MIC) determinations by the broth microdilution method. To verify cellular growth, the colour-changing dye Resazurin was applied, the Optical Densities were measured on a spectrophotometer, and both were compared to Clinical and Laboratory Standards Institute (CLSI) Gold Standard method (visual MIC determination). Percentages of essential and categorical agreements and interpretative categorical errors were calculated within each method (intra-reading) and between them (inter-reading). The Gold Standard visual reading demonstrated 100% of essential and categorical intra-reading agreements for Amikacin, and there was no error when compared with the alternative methods. For Ciprofloxacin, the comparison between the Gold Standard and the Spectrophotometric reading showed 91.5% of essential agreement. In the categorical intra-reading analysis for Minocycline, there were 88.1 and 91.7% in the Gold Standard and in the Spectrophotometric readings, respectively, and 86.4% of concordance between them. High rates of categorical agreement were also observed on the Trimethoprim-Sulfamethoxazole analyses, with 93.7% for the Gold Standard, 84.9% for the Resazurin readings, and 80.5% between them. Conclusions The alternative methods with Resazurin and Spectrophotometric readings showed high agreement rates with the Gold Standard.

Staphylococcus aureus is an important cause of udder infections in dairy herds. Both lactational and dry cow therapy are part of Staph. aureus control programs. Reported cure rates for Staph. aureus mastitis vary considerably. The probability of cure depends on cow, pathogen, and treatment factors. Cure rates decrease with increasing age of the cow, increasing somatic cell count, increasing duration of infection, increasing bacterial colony counts in milk before treatment, and increasing number of quarters infected. Staphylococcus aureus mastitis in hind quarters has a low cure rate compared with front quarters. Antimicrobial treatment of intramammary infections with penicillin-resistant Staph. aureus strains results in a lower cure rate for treatment with either β-lactam or non-β-lactam antibiotics. Other strain-specific factors may affect the probability of cure but routine diagnostic methods for use in bacteriology laboratories or veterinary practices are not yet available. The most important treatment factor affecting cure is treatment duration. Increased duration of treatment is associated with increased chance of cure. Economically, extended treatment is not always justified, even when indirect effects of treatment such as prevention of contagious transmission are taken into consideration. Usefulness of treatment trials could be improved by standardization of case definitions, consideration of host and strain factors, and sufficient statistical power. Treatment of young animals with penicillin-sensitive Staph. aureus infections is often justified based on bacteriological cure and economic outcome, whereas treatment of older animals, chronic infections, or penicillin-resistant isolates should be discouraged.

Background Novel, rapid blood culture diagnostics can provide faster antibiotic susceptibility results (AST) compared to standard methods but their impact on clinical outcomes is unclear and not assessed in many prospective clinical trials. Methods This study is a two-arm, multicenter, multinational, prospective randomized controlled clinical trial conducted in countries with high antibiotic resistance rates including Greece, India, Israel, and Spain. Nine hundred hospitalized subjects who have blood cultures collected as part of routine clinical care with growth of Gram-negative bacilli (GNB) will be randomized 1:1 to blood culture evaluation using standard of care (SOC) AST vs. a rapid phenotypic AST method, VITEK REVEAL™ in addition to SOC AST. Subjects in both study arms will be reviewed by antibiotic stewardship clinicians who will recommend changes to antibiotic therapy, if indicated. The primary outcome is a composite three-category Desirability of Outcome Ranking (DOOR) defined using three ordered levels: alive without deleterious events, alive with at least one deleterious event, and death. Key secondary outcomes include mortality, length of stay, and time to antibiotic escalation or de-escalation within 3 days of randomization. Exploratory outcomes include a five-category DOOR, categorial agreement between VITEK REVEAL™ and SOC testing, clinician compliance with antibiotic stewardship recommendations, and desirability of treatment selection based on antibiotic spectrum, activity, and bloodstream isolate susceptibility profile (DOOR MAT). The primary analysis will be conducted on the modified intention-to-treat population. Discussion This trial will evaluate whether use of a rapid phenotypic AST method improves outcomes compared to use of conventional methods for patients with Gram-negative bloodstream infections in clinical settings with high antibiotic resistance rates. Trial registration ClinicalTrials.gov ID NCT06174649. Registered on Dec 18 2023. Protocol version Number 20-0021, version 5.0, 11-April-2024.

BackgroundAmoxicillin, metronidazole, proton pump inhibitor, bismuth quadruple therapy had been shown to reliably achieve high eradication rates. The role of individual components remains undefined.AimTo identify the additional benefit/role of bismuth in amoxicillin, metronidazole, proton pump inhibitor, bismuth quadruple therapy for Helicobacter pylori (H. pylori) treatment.MethodsThis was a non-inferiority factorial design trial. Treatment-naive H. pylori-infected subjects were randomly (1:1) assigned to receive 14-day amoxicillin- and metronidazole-containing triple therapy consisting of esomeprazole 20 mg twice a day, amoxicillin 1 g, and metronidazole 400 mg both thrice daily with or without 220 mg bismuth twice a day. Six weeks after treatment, H. pylori eradication was assessed by 13C-urea breath test. Antimicrobial susceptibility was assessed by the twofold agar dilution method.ResultsFrom July 2018 to June 2019, a total of two hundred and sixteen subjects were randomized. Both therapies achieved high eradication rates. Per-protocol with bismuth = 97.9% (94/96, 95% CI 95.1–100%) and without bismuth = 94.7% (90/95, 95% CI 90.3–99.1%) (P = 0.43). Intent-to-treat analysis = 90.7% (98/108, 95% CI 85.2–96.2%) versus 88.9% (96/108, 95% CI 82.8–95.0%) with and without bismuth (P = 0.65). The two regimens were not inferior by intent-to-treat or per-protocol analyses. Metronidazole resistance did not affect the efficacy of either therapy.ConclusionNeither the presence nor absence of bismuth or metronidazole resistance reduced the effectiveness of triple therapy containing esomeprazole 20 mg twice a day, amoxicillin 1 g, and metronidazole 400 mg thrice daily in this population. The clinical trial was registered with ClinicalTrials.gov, NCT03557437.

Background and Objective Sepsis and continuous renal replacement therapy (CRRT) can both significantly affect antifungal pharmacokinetics. This study aimed to describe the pharmacokinetics of caspofungin in critically ill patients during different CRRT modes. Methods Patients receiving caspofungin and undergoing continuous veno-venous haemofiltration (CVVH) or haemodiafiltration (CVVHDF) were eligible to take part in the study. Blood samples were collected at seven sampling times during a dosing interval. Demographics and clinical data were recorded. Population pharmacokinetic analysis and Monte-Carlo simulation were undertaken using Pmetrics. Results Twelve pharmacokinetic profiles from nine patients were analysed. The caspofungin CRRT clearance (CL) was 0.048 ± 0.12 L/h for CVVH and 0.042 ± 0.042 L/h for CVVHDF. A two-compartment linear model best described the data. Patient weight was the only covariate affecting drug CL and central volume. The mean (standard deviation) parameter estimates were 0.64 ± 0.12 L/h for CL, 9.35 ± 3.56 L for central volume, 0.25 ± 0.19 per h for the rate constant for drug distribution from central to peripheral compartments and 0.19 ± 0.10 per h from peripheral to central compartments. Based on simulation results, a caspofungin 100 mg loading dose followed by a 50 mg maintenance dose for patients with a total body weight of ≤80 kg best achieved the pharmacokinetic/PD targets whilst a 70 mg maintenance dose was required for patients with a weight of >80 kg. Conclusion No caspofungin dosing adjustment is necessary for patients undergoing either form of CRRT. However, higher than recommended loading doses of caspofungin are required to achieve pharmacokinetic/pharmacodynamic targets in critically ill patients. Registration: ClinicalTrials.gov Identifier NCT01403220