Clinical efficacy of fosfomycin combinations against a variety of gram-positive cocci / Eficacia clínica de las combinaciones de fosfomicina contra una variedad de cocos grampositivos

Introduction: Over recent years we have witnessed an increase in the resistance of microorganisms to the available antimicrobials and a decrease in the number of new antimicrobials. Fosfomycin is a safe and cheap broad-spectrum antibiotic which has shown very promising results in combination therapy, mainly against gram-negative microorganisms. Little is known, however, about its clinical efficacy against gram-positive microorganisms. Methods: We performed a retrospective review of all patients with severe gram-positive infections who received fosfomycin as part of their treatment from 2011 to 2017. We also performed in vitro time-kill assays to study the behaviour of fosfomycin with different antimicrobials against two strains of methicillin-resistant Staphylococcus aureus (MRSA) and two strains of methicillin-susceptible S. aureus (MSSA). Results: Seventy-five patients were treated with different fosfomycin combinations. Among them, 61 (81%) were successfully treated. Daptomycin plus fosfomycin was the most effective combination. Overall, the treatment with fosfomycin was safe, and side effects were minor. There was only one major side effect that resolved after discontinuation of therapy. Time-kill studies demonstrated increased activity of fosfomycin combinations, with daptomycin-fosfomycin being the most active combination against both MRSA and MSSA strains. Conclusions: Our results suggest that antimicrobial combinations including fosfomycin are an alternative and effective approach for gram-positive infections

Introducción: En los últimos años se ha ido produciendo un aumento de la resistencia de los microorganismos a los antimicrobianos disponibles, y una disminución en el número de nuevos antimicrobianos. La fosfomicina es un antibiótico seguro y barato con un amplio espectro de actividad, que ha mostrado resultados muy prometedores en terapia de combinación, principalmente contra microorganismos gramnegativos. Sin embargo, poco se conoce sobre su eficacia clínica frente a microorganismos grampositivos. Métodos: Revisión retrospectiva de todos los pacientes con infecciones graves por microorganismos grampositivos que recibieron fosfomicina como parte de su tratamiento, entre los años 2011 y 2017. También se realizaron curvas de letalidad in vitro para estudiar el comportamiento de la fosfomicina con diferentes antimicrobianos, frente a 2 cepas de Staphylococcus aureus resistentes a meticilina (SARM) y 2 cepas de S. aureus sensible a la meticilina (SASM). Resultados: Setenta y cinco pacientes recibieron tratamiento con diferentes combinaciones de fosfomicina. De ellos, 61 (81%) fueron tratados con éxito. Daptomicina más fosfomicina fue la combinación más efectiva. En general, el tratamiento con fosfomicina fue seguro, con efectos secundarios menores. Hubo solo un efecto secundario importante que se resolvió tras la suspensión del tratamiento. Las curvas de letalidad demostraron buena actividad de las combinaciones de fosfomicina, siendo la combinación daptomicina-fosfomicina la más activa, tanto frente a las cepas de SARM como de SASM. Conclusiones: Nuestros resultados sugieren que combinaciones con fosfomicina, pueden ser un tratamiento alternativo y efectivo en infecciones por grampositivos

Clinical efficacy of fosfomycin combinations against a variety of gram-positive cocci.

INTRODUCTION: Over recent years we have witnessed an increase in the resistance of microorganisms to the available antimicrobials and a decrease in the number of new antimicrobials. Fosfomycin is a safe and cheap broad-spectrum antibiotic which has shown very promising results in combination therapy, mainly against gram-negative microorganisms. Little is known, however, about its clinical efficacy against gram-positive microorganisms. METHODS: We performed a retrospective review of all patients with severe gram-positive infections who received fosfomycin as part of their treatment from 2011 to 2017. We also performed in vitro time-kill assays to study the behaviour of fosfomycin with different antimicrobials against two strains of methicillin-resistant Staphylococcus aureus (MRSA) and two strains of methicillin-susceptible S. aureus (MSSA). RESULTS: Seventy-five patients were treated with different fosfomycin combinations. Among them, 61 (81%) were successfully treated. Daptomycin plus fosfomycin was the most effective combination. Overall, the treatment with fosfomycin was safe, and side effects were minor. There was only one major side effect that resolved after discontinuation of therapy. Time-kill studies demonstrated increased activity of fosfomycin combinations, with daptomycin-fosfomycin being the most active combination against both MRSA and MSSA strains. CONCLUSIONS: Our results suggest that antimicrobial combinations including fosfomycin are an alternative and effective approach for gram-positive infections.

Clinical predictors of candidemia in medical non-neutropenic, non-ICU patients. The CaMed score.

INTRODUCTION: Candida species are the leading cause of invasive fungal infections in hospitalised patients and are the fourth most common isolates recovered from patients with bloodstream infection. Few data exist on risk factors for candidemia in non-ICU patients. We performed a population-based case-control study to evaluate the main predictors for candidemia in non-ICU patients. METHODS AND FINDINGS: We included all non-neutropenic, non-critically ill and non-surgical adult patients with candidemia between January 2010 and June 2014. Patients with positive, non-candidal blood culture obtained at the same day (±2 days) were selected as controls. Cases and controls were matched according to hospital ward and clinical characteristics. Risk factors for candidemia were identified through a logistic regression. We included 56 candidemic and 512 bacteriemic non-candidemic patients. Most of candidemic patients (52) had received antibiotics prior to candidemia. Among them, the 30-day mortality rate was 34% (19/56). Multivariate analysis identified male sex, prior use of steroids, prior use of antibiotics, total parenteral nutrition and urinary catheterisation as independent predictors of candidemia. To develop the CaMed score, we rounded up weights of different risk factors as follows; total parenteral nutrition (+2), prior antibiotic therapy (+5), each of the other risk factors (+1). A score ≥ 7 identified patients at high risk of candidemia (P < 0.001; RR 29.805; CI 95% 10.652-83.397; sensitivity 79.2, specificity 82.6%, Youden index 0,62). CONCLUSIONS: Our set of easy independent predictors of candidemia in non-neutropenic, non-ICU, non-surgical patients provide a rationale for early initiation of antifungals and could reduce candidemia-related mortality.

In vitro efficacy of daptomycin and teicoplanin combined with ethanol, clarithromycin or gentamicin as catheter lock solutions.

BACKGROUND: Despite widespread use, optimum choice of antimicrobial agents, concentrations, combinations and exposure times have not been determined for antibiotic lock technique (ALT). Our objective was to evaluate the efficacy of different antibiotic combinations using an in vitro model of catheter-related infection. Daptomycin (DAP) 5 mg/mL, teicoplanin (TEC) 5 mg/mL, both alone and combined with gentamicin (GM) 2.5 mg/mL, clarythromycin (CLA) 5 mg/mL or ethanol 35 % were evaluated against four clinical strains of methicillin resistant coagulase negative staphylococci. Lock solutions were renewed every 24 h. RESULTS: After 72 h catheters were reincubated with culture media to investigate bacterial regrowth. All antibiotic combinations resulted in significant reductions (p < 0.05) of Log(10) cfu/mL at 72 h for both organisms compared with controls. DAP resulted in significant reductions of Log(10) for all organism versus TEC (p = 0.001). Only DAP reached the limit of detection at 72 h, however did not prevent regrowth after 24 h of ALT removal. DAP + Ethanol and TEC + ethanol eradicated biofilm at 72 h, but only DAP + ethanol (against all strains) and DAP + CLA (against two strains) prevented regrowth at 24 h after ALT removal. CONCLUSIONS: Based on these data, ALT with DAP + ethanol and DAP + CLA should be explored in clinical trials.

Multicentre evaluation of glycated haemoglobin (HbA1c) of Roche Diagnostics in Andalusia.

BACKGROUND: A Spanish multicentre evaluation of the third generation of Roche Diagnostics immunoturbidimetric inhibition method (TINIA) is presented for quantification of haemoglobin A1c (HbA1c) in whole blood. METHODS: The analytical performance of the TINIA test was evaluated and blood sample results were compared with two other widely used analysers, Bio-Rad Variant II and Adams Arkray HA-8160, based on HPLC. RESULTS: Within- and between-batch imprecision (coefficients of variation (CVs)) for HbA1c levels of 5, 6, 7 and 8% were 0.77, 1.23, 1.35 and 1.26% and 2.38, 1.51, 1.76 and 2.16%, respectively. For low (5.4% A1c) and high (10.1% A1c) quality control samples, the within and between-batch %CV were: 1.26; 1.43 and 2; 1.71 respectively. The test met the expected performance in most aspects, except for linearity, that is under the reported range, and HbF interferences, detected for levels over 7.5%. There was a good concordance between the results of TINIA and Variant-IIt in the whole range and with HA-8160 only up to levels of 9%. Between-batch imprecision suggests more frequent calibrations than reported by the provider to maintain variability within the limits established by clinical practice guidelines. CONCLUSIONS: The assay meets the necessary quality standards for routine use, as long as we keep the analytical variability within narrow limits. The results may be interchangeable with the tested HPLC systems, but HbF interference is not detected and it happens at lower levels than reported.

The potential pathogenicity of chlorhexidine-sensitive Acanthamoeba strains isolated from contact lens cases from asymptomatic individuals in Tenerife, Canary Islands, Spain.

Pathogenic strains of the genus Acanthamoeba are causative agents of a serious sight-threatening infection of the eye known as Acanthamoeba keratitis. The prevalence of this infection has risen in the past 20 years, mainly due to the increase in number of contact lens wearers. In this study, the prevalence of Acanthamoeba in a risk group constituted by asymptomatic contact lens wearers from Tenerife, Canary Islands, Spain, was evaluated. Contact lenses and contact lens cases were analysed for the presence of Acanthamoeba isolates. The isolates' genotypes were also determined after rDNA sequencing. The pathogenic potential of the isolated strains was subsequently established using previously described molecular and biochemical assays, which allowed the selection of three strains with high pathogenic potential. Furthermore, the sensitivity of these isolates against two standard drugs, ciprofloxacin and chlorhexidine, was analysed. As the three selected strains were sensitive to chlorhexidine, its activity and IC(50) were evaluated. Chlorhexidine was found to be active against these strains and the obtained IC(50) values were compared to the concentrations of this drug present in contact lens maintenance solutions. It was observed that the measured IC(50) was higher than the concentration found in these maintenance solutions. Therefore, the ineffectiveness of chlorhexidine-containing contact lens maintenance solutions against potentially pathogenic strains of Acanthamoeba is demonstrated in this study.

Detection of four adenovirus serotypes within water-isolated strains of Acanthamoeba in the Canary Islands, Spain.

We surveyed 236 potentially pathogenic Acanthamoeba strains, isolated from water sources in the Canary Islands, for the presence of human adenoviruses (HAdV) using a polymerase chain reaction (PCR)-based typing assay. A total of 34 of these strains were found to be positive for adenovirus belonging to four different HAdV serotypes (HAdV-1, 2, 8, and 37). We found that HAdV-2 was the most frequently encountered serotype amongst the Acanthamoeba strains, and their identification was confirmed by a nested PCR specific for this serotype. We showed that Acanthamoeba genotype T4 was highly associated with serotype HAdV-2, whereas Acanthamoeba genotype T3 was most often associated with adenovirus serotypes related to ocular diseases. Based on these data, we suggest that Acanthamoeba should be considered as a potential reservoir and perhaps even a transmitter of adenoviruses to human and other secondary hosts.

Enterocytozoon bieneusi (microsporidia) in clinical samples from immunocompetent individuals in Tenerife, Canary Islands, Spain.

Microsporidia are newly emerging pathogens of humans and animals, with Enterocytozoon bieneusi being the most common causal agent in human microsporidiosis. To determine the presence of E. bieneusi, 273 clinical samples (40 urine, 156 stools, 37 sputum, 9 bronchial aspirates, 5 bronchial washes and 26 pleural fluids) from immunocompetent patients, mainly suffering diarrhoea or pneumonia, in Tenerife, Canary Islands, Spain were analysed using light microscopy after staining with Weber's chromotrope and by PCR/hybridisation with a specific probe designed to increase the sensitivity of the identification. In this study, detection of E. bieneusi after PCR/hybridisation is reported in 18 (11.54%) of 156 stool samples, 1 (2.5%) of 40 urine samples and 6 (16.22%) of 37 sputum samples. To our knowledge, these are the first reports of E. bieneusi in this subtropical region, showing the increased importance of these parasites as emerging pathogens worldwide.