Intravenous fosfomycin-back to the future. Systematic review and meta-analysis of the clinical literature

Objectives: We conducted a systematic review and meta-analysis to summarize the clinical evidence and usage patterns of intravenous fosfomycin from its development to the present time. Methods: PubMed, the Cochrane Library and local journals were searched for relevant studies reporting aggregated data of intravenous fosfomycin use in adults and children, with no restrictions regarding study design. Single case reports were excluded. Data were systematically abstracted for all included studies. Clinical and microbiological efficacy from randomized controlled and comparative observational studies were synthesized using meta-analysis to calculate pooled effect sizes. Results: In all, 128 studies on intravenous fosfomycin in 5527 patients were evaluated. Fosfomycin was predominantly used for sepsis/bacteraemia, urinary tract, respiratory tract, bone and joint, and central nervous system infections. No difference in clinical (OR 1.44, 95% CI 0.96-2.15) or microbiological (OR 1.28, 95% CI 0.82-2.01) efficacy between fosfomycin and other antibiotics was observed in comparative trials. The pooled estimate for resistance development during fosfomycin monotherapy was 3.4% (95% CI 1.8%-5.1%). Fosfomycin showed a favourable safety profile, with generally mild adverse events not requiring discontinuation of treatment. Included studies explored intravenous fosfomycin as an antistaphylococcal agent in monotherapy and combination therapy, whereas studies from 1990 focused on combination therapy (fosfoymcin + beta-lactams or aminoglycosides) for challenging infections frequently caused by multidrug-resistant organisms. Conclusion: Intravenous fosfomycin can play a vital role in the antibiotic armamentarium, given its long history of effective and safe use. However, well-designed randomized controlled trials are still desired. (C) 2016 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases

Clinical profiles of patients colonized or infected with extended-spectrum beta-lactamase producing Enterobacteriaceae isolates: a 20 month retrospective study at a Belgian University Hospital

<p>Abstract</p> <p>Background</p> <p>Description of the clinical pictures of patients colonized or infected by ESBL-producing <it>Enterobacteriaceae </it>isolates and admitted to hospital are rather scarce in Europe. However, a better delineation of the clinical patterns associated with the carriage of ESBL-producing isolates may allow healthcare providers to identify more rapidly at risk patients. This matter is of particular concern because of the growing proportion of ESBL-producing <it>Enterobacteriaceae </it>species isolates worldwide.</p> <p>Methods</p> <p>We undertook a descriptive analysis of 114 consecutive patients in whom ESBL-producing <it>Enterobacteriaceae </it>isolates were collected from clinical specimens over a 20-month period. Clinical data were obtained through retrospective analysis of medical record charts. Microbiological cultures were carried out by standard laboratory methods.</p> <p>Results</p> <p>The proportion of ESBL-producing <it>Enterobacteriaceae </it>strains after exclusion of duplicate isolates was 4.5% and the incidence rate was 4.3 cases/1000 patients admitted. Healthcare-associated acquisition was important (n = 104) while community-acquisition was less frequently found (n = 10). Among the former group, two-thirds of the patients were aged over 65 years and 24% of these were living in nursing homes. Sixty-eight (65%) of the patients with healthcare-associated ESBL, were considered clinically infected. In this group, the number and severity of co-morbidities was high, particularly including diabetes mellitus and chronic renal insufficiency. Other known risk factors for ESBL colonization or infection such as prior antibiotic exposure, urinary catheter or previous hospitalisation were also often found. The four main diagnostic categories were: urinary tract infections, lower respiratory tract infections, septicaemia and intra-abdominal infections. For hospitalized patients, the median hospital length of stay was 23 days and the average mortality rate during hospitalization was 13% (Confidence Interval 95%: 7-19). <it>Escherichia coli</it>, by far, accounted as the most common ESBL-producing <it>Enterobacteriaceae </it>species (77/114; [68%]) while CTX-M-1 group was by far the most prevalent ESBL enzyme (n = 56).</p> <p>Conclusion</p> <p>In this retrospective study, the clinical profiles of patients carrying healthcare-associated ESBL-producing <it>Enterobacteriacae </it>is characterized by a high prevalence rate of several major co-morbidities and potential known risk factors. Both, the length of hospital stay and overall hospital mortality rates were particularly high. A prospective case-control matched study should be designed and performed in order to control for possible inclusion bias.</p

Association of Patients’ Epidemiological Characteristics and Comorbidities with Severity and Related Mortality Risk of SARS-CoV-2 Infection: Results of an Umbrella Systematic Review and Meta-Analysis

The objective of this study was to assess the association between patients’ epidemiological characteristics and comorbidities with SARS-CoV-2 infection severity and related mortality risk. An umbrella systematic review, including a meta-analysis examining the association between patients’ underlying conditions and severity (defined as need for hospitalization) and mortality of COVID-19, was performed. Studies were included if they reported pooled risk estimates of at least three underlying determinants for hospitalization, critical disease (ICU admission, mechanical ventilation), and hospital mortality in patients diagnosed with SARS-CoV-2 infection. Evidence was summarized as pooled odds ratios (pOR) for disease outcomes with 95% confidence intervals (95% CI). Sixteen systematic reviews investigating the possible associations of comorbidities with severity or death from COVID-19 disease were included. Hospitalization was associated with age &gt; 60 years (pOR 3.50; 95% CI 2.97–4.36), smoking habit (pOR 3.50; 95% CI 2.97–4.36), and chronic pulmonary disease (pOR 2.94; 95% CI 2.14–4.04). Chronic pulmonary disease (pOR 2.82; 95% CI 1.92–4.14), cerebrovascular disease (pOR 2.74; 95% CI 1.59–4.74), and cardiovascular disease (pOR 2.44; 95% CI 1.97–3.01) were likely to be associated with increased risk of critical COVID-19. The highest risk of mortality was associated with cardiovascular disease (pOR 3.59; 95% CI 2.83–4.56), cerebrovascular disease (pOR 3.11; 95% CI 2.35–4.11), and chronic renal disease (pOR 3.02; 95% CI 2.61–3.49). In conclusion, this umbrella systematic review provides a comprehensive summary of meta-analyses examining the impact of patients’ characteristics on COVID-19 outcomes. Elderly patients and those cardiovascular, cerebrovascular, and chronic renal disease should be prioritized for pre-exposure and post-exposure prophylaxis and early treatment

Biofilm formation at the solid-liquid and air-liquid interfaces by Acinetobacter species

Abstract Background: The members of the genus Acinetobacter are Gram-negative cocobacilli that are frequently found in the environment but also in the hospital setting where they have been associated with outbreaks of nosocomial infections. Among them, Acinetobacter baumannii has emerged as the most common pathogenic species involved in hospital-acquired infections. One reason for this emergence may be its persistence in the hospital wards, in particular in the intensive care unit; this persistence could be partially explained by the capacity of these microorganisms to form biofilm. Therefore, our main objective was to study the prevalence of the two main types of biofilm formed by the most relevant Acinetobacter species, comparing biofilm formation between the different species. Findings: Biofilm formation at the air-liquid and solid-liquid interfaces was investigated in different Acinetobacter spp. and it appeared to be generally more important at 25°C than at 37°C. The biofilm formation at the solid-liquid interface by the members of the ACB-complex was at least 3 times higher than the other species (80-91% versus 5-24%). In addition, only the isolates belonging to this complex were able to form biofilm at the air-liquid interface; between 9% and 36% of the tested isolates formed this type of pellicle. Finally, within the ACB-complex, the biofilm formed at the air-liquid interface was almost 4 times higher for A. baumannii and Acinetobacter G13TU than for Acinetobacter G3 (36%, 27% & 9% respectively). Conclusions: Overall, this study has shown the capacity of the Acinetobacter spp to form two different types of biofilm: solid-liquid and air-liquid interfaces. This ability was generally higher at 25°C which might contribute to their persistence in the inanimate hospital environment. Our work has also demonstrated for the first time the ability of the members of the ACB-complex to form biofilm at the air-liquid interface, a feature that was not observed in other Acinetobacter species

Nosocomial acquisition of methicillin-resistant Staphyloccocus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL) Enterobacteriaceae in hospitalised patients: a prospective multicenter study

The risk of acquisition of antibiotic resistant-bacteria during or shortly after antibiotic therapy is still unclear and it is often confounded by scarce data on antibiotic usage.Primary objective of the study is to compare rates of acquisition of methicillin-resistant Staphylococcus aureus and extended spectrum beta-lactamase-producing Enterobacteriaceae in hospitalised patients, after starting antibiotic therapy

Global dissemination of a multidrug resistant Escherichia coli clone.

Escherichia coli sequence type 131 (ST131) is a globally disseminated, multidrug resistant (MDR) clone responsible for a high proportion of urinary tract and bloodstream infections. The rapid emergence and successful spread of E. coli ST131 is strongly associated with several factors, including resistance to fluoroquinolones, high virulence gene content, the possession of the type 1 fimbriae FimH30 allele, and the production of the CTX-M-15 extended spectrum β-lactamase (ESBL). Here, we used genome sequencing to examine the molecular epidemiology of a collection of E. coli ST131 strains isolated from six distinct geographical locations across the world spanning 2000-2011. The global phylogeny of E. coli ST131, determined from whole-genome sequence data, revealed a single lineage of E. coli ST131 distinct from other extraintestinal E. coli strains within the B2 phylogroup. Three closely related E. coli ST131 sublineages were identified, with little association to geographic origin. The majority of single-nucleotide variants associated with each of the sublineages were due to recombination in regions adjacent to mobile genetic elements (MGEs). The most prevalent sublineage of ST131 strains was characterized by fluoroquinolone resistance, and a distinct virulence factor and MGE profile. Four different variants of the CTX-M ESBL-resistance gene were identified in our ST131 strains, with acquisition of CTX-M-15 representing a defining feature of a discrete but geographically dispersed ST131 sublineage. This study confirms the global dispersal of a single E. coli ST131 clone and demonstrates the role of MGEs and recombination in the evolution of this important MDR pathogen

Risk factors for treatment failure and mortality among hospitalized patients with complicated urinary tract infection: A multicenter retrospective cohort study (RESCUING study group)

Background. Complicated urinary tract infections (cUTIs) are responsible for a major share of all antibiotic consumption in hospitals. We aim to describe risk factors for treatment failure and mortality among patients with cUTIs. Methods. A multinational, multicentre retrospective cohort study, conducted in 20 countries in Europe and the Middle East. Data were collected from patients' files on hospitalised patients with a diagnosis of cUTI during 2013-2014. Primary outcome was treatment failure, secondary outcomes included 30 days all-cause mortality,among other outcomes. Multivariable analysis using a logistic model and the hospital as a random variable was performed to identify independent predictors for these outcomes. Results. A total of 981 patients with cUTI were included. Treatment failure was observed in 26.6% (261/981), all cause 30-day mortality rate was 8.7% (85/976), most of these in patients with catheter related UTI (CaUTI). Risk factors for treatment failure in multivariable analysis were ICU admission (OR 5.07, 95% CI 3.18-8.07), septic shock (OR 1.92, 95% CI 0.93-3.98), corticosteroid treatment (OR 1.92, 95% CI 1.12-3.54), bedridden (OR 2.11, 95%CI 1.4-3.18), older age (OR 1.02, 95% CI 1.0071.03-), metastatic cancer (OR 2.89, 95% CI 1.46-5.73) and CaUTI (OR 1.48, 95% CI 1.04-2.11). Management variables, such as inappropriate empirical antibiotic treatment or days to starting antibiotics were not associated with treatment failure or 30-day mortality. More patients with pyelonephritis were given appropriate empirical antibiotic therapy than other CaUTI [110/171; 64.3% vs. 116/270; 43%, p &lt;0.005], nevertheless, this afforded no advantage in treatment failure rates nor mortality in these patients. Conclusions. In patients with cUTI we found no benefit of early appropriate empirical treatment on survival rates or other outcomes. Physicians might consider supportive treatment and watchful waiting in stable patients until the causative pathogen is defined

High prevalence of fecal carriage of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae in a pediatric unit in Madagascar

<p>Abstract</p> <p>Background</p> <p>Extended-spectrum β-lactamase (ESBL)-producing <it>Enterobacteriaceae </it>have spread worldwide but there are few reports on carriage in hospitals in low-income countries. ESBL-producing <it>Enterobacteriaceae </it>(ESBL-PE) have been increasingly isolated from nosocomial infections in Antananarivo, Madagascar.</p> <p>Methods</p> <p>we conducted a prevalence survey in a pediatric unit from March to April 2008 Patient rectal swabs were sampled on the first and the last day of hospitalization. Medical staff and environment were also sampled. Rectal and environmental swabs were immediately plated onto Drigalski agar supplemented with 3 mg/liter of ceftriaxon.</p> <p>Results</p> <p>Fecal carriage was detected in 21.2% of 244 infants on admission and 57.1% of 154 on discharge, after more than 48 hours of hospitalization (p < 0.001). The species most frequently detected on admission were <it>Escherichia coli and Klebsiella pneumoniae </it>(36.9%), whereas, on discharge, <it>K. pneumoniae </it>was the species most frequently detected (52.7%). ESBL-associated resistances were related to trimethoprim-sulfamethoxazole (91.3%), gentamicin (76.1%), ciprofloxacin (50.0%), but not to amikacin and imipenem. The increased prevalence of carriage during hospitalization was related to standard antimicrobial therapy.</p> <p>Conclusion</p> <p>The significant emergence of multidrug-resistant enteric pathogens in Malagasy hospitals poses a serious health threat requiring the implementation of surveillance and control measures for nosocomial infections.</p