Fosfomycin in continuous or prolonged infusion for systemic bacterial infections: a systematic review of its dosing regimen proposal from in vitro, in vivo and clinical studiesAntonello, Roberta Maria; Di Bella, Stefano; Maraolo, Alberto Enrico; Luzzati, Roberto
doi: 10.1007/s10096-021-04181-xpmid: 33604721
Fosfomycin (FOS) administered intravenously has been recently rediscovered for the treatment of systemic infections due to multidrug-resistant bacteria. Its pharmacokinetic properties suggest a time-dependent dosing schedule with more clinical benefits from prolonged (PI) or continuous infusion (CI) than from intermittent infusion. We revised literature concerning PI and CI FOS to identify the best dosing regimen based on current evidence. We performed a MEDLINE/PubMed search. Ninety-one studies and their pertinent references were screened. Seventeen studies were included in the present review. The activity of FOS against Gram-negative and Gram-positive bacteria was evaluated in fourteen and five studies, respectively. Six studies evaluated FOS activity in combination with another antibiotic. Daily dosing of 12, 16, 18 or 24 g, administered with different schedules, were investigated. These regimens resulted active against the tested isolates in most cases. Emergence of resistant isolates has been shown to be preventable through the coadministration of another active antibiotic. FOS is a promising option to treat systemic infections caused by multidrug-resistant bacteria. Coadministration with another active molecule is required to prevent the emergence of resistant bacterial strains. The results of our review suggest that a therapeutic regimen including a loading dose of FOS 8 g followed by a daily dose of 16 g or 24 g CI could be the best therapeutic approach for patients with normal renal function. The dosing regimens in patients with renal insufficiency and CI or PI superiority compared with intermittent infusion in clinical settings should be further investigated.
Antibiotic susceptibility and molecular analysis of invasive Neisseria meningitidis recovered in the Republic of Ireland, 1996 to 2016Bennett, Désirée E.; Meyler, K. L.; Cafferkey, M. T.; Cunney, R. J.
doi: 10.1007/s10096-020-04114-0pmid: 33403566
This study examined the antimicrobial susceptibility of invasive meningococcal disease (IMD)–associated Neisseria meningitidis recovered in the Republic of Ireland between 1996 and 2016. In total, 1359 isolates representing over one-third of all laboratory-confirmed cases of IMD diagnosed each epidemiological year (EY; July 1–June 30) were analysed. All isolates were susceptible to ciprofloxacin, rifampicin and cefotaxime and 74% and 87% were susceptible to sulphonamide and penicillin, respectively. The proportion of isolates exhibiting reduced susceptibility to penicillin increased significantly during the study with no evidence of major clonal expansion or horizontal spread of a specific penA allele. Greater diversity observed among recently recovered meningococci and specifically among isolates exhibiting reduced penicillin susceptibility contributed to the overall increase in penA allele diversity throughout. The emergence and dissemination of strains with phenotypic and genotypic reduced susceptibility to penicillin increase the need for continued surveillance of antimicrobial susceptibility of meningococci in the Republic of Ireland especially in view of the recommendation of penicillin G as empiric treatment of choice for pre-hospital management.
Secular trends in the epidemiology and clinical characteristics of Enterococcus faecalis infective endocarditis at a referral center (2007–2018)Escolà-Vergé, Laura; Fernández-Hidalgo, Nuria; Larrosa, María Nieves; Fernandez-Galera, Ruben; Almirante, Benito
doi: 10.1007/s10096-020-04117-xpmid: 33404892
The aim of the study was to analyze the epidemiological and clinical changes in EFIE. All definite IE episodes treated at a referral center between 2007 and 2018 were registered prospectively, and a trend test was used to study etiologies over time. EFIE cases were divided into three periods, and clinical differences between them were analyzed. All episodes of E. faecalis monomicrobial bacteremia (EFMB) between 2010 and 2018 and the percentage of echocardiograms performed were retrospectively collected. Six hundred forty-eight IE episodes were studied. We detected an increase in the percentage of EFIE (15% in 2007, 25.3% in 2018, P = 0.038), which became the most prevalent causative agent of IE during the last study period. One hundred and eight EFIE episodes were analyzed (2007–2010, n = 30; 2011–2014, n = 22; 2015–2018, n = 56). The patients in the last period were older (median 70.9 vs 66.5 vs 76.3 years, P = 0.015) and more frequently had an abdominal origin of EFIE (20% vs 13.6% vs 42.9%, P = 0.014), fewer indications for surgery (63.3% vs 54.6% vs 32.1%, P = 0.014), and non-significantly lower in-hospital mortality (30% vs 18.2% vs 12.5%, P = 0.139). There was an increase in the percentage of echocardiograms performed in patients with EFMB (30% in 2010, 51.2% in 2018, P = 0.014) and EFIE diagnoses (15% in 2010, 32.6% in 2018, P = 0.004). E. faecalis is an increasing cause of IE in our center, most likely due to an increase in the percentage of echocardiograms performed. The factors involved in clinical changes in EFIE should be thoroughly studied.
Serodiagnosis of Lyme borreliosis—is IgM in serum more harmful than helpful?Hillerdal, Henrik; Henningsson, Anna J.
doi: 10.1007/s10096-020-04093-2pmid: 33409833
Interpretation of serological findings in suspected Lyme borreliosis (LB) may be challenging and IgM reactivities in serum are often unspecific (false positive). There is a risk for overdiagnosis of LB, inadequate use of antibiotics, and potential delay of proper diagnosis. In this study, we evaluated the diagnostic value of IgM analysis in serum and IgM antibody index (AI) in LB diagnosis. This was a retrospective observational study regarding Borrelia-specific antibodies in serum and Borrelia-specific AI in LB investigations being made during 2017 in Jönköping County, Sweden. Medical records of 610 patients with detectable anti-Borrelia antibodies in serum (IgM and/or IgG) and 15 patients with elevated Borrelia-specific AI were retrospectively scrutinized, and the compliance to current European recommendations was assessed. Among the 610 patients, only 30% were tested according to the European recommendations. Within this group of tests taken correctly, 50% of the LB diagnoses in patients with isolated IgM reactivity in serum were retrospectively assessed as incorrect (LB unlikely). Three pediatric patients with clinical and laboratory findings suggestive of Lyme neuroborreliosis (LNB) had elevated IgM AI alone. Serological testing without distinct clinical signs/symptoms consistent with LB contributes to most misdiagnoses. Isolated IgM positivity in serum shows limited clinical value and needs further assessment before being reported by the laboratory. Detection of IgM in combination with IgG antibodies in serum shows no clinical enhancement for correct LB diagnosis compared to isolated IgG positivity. However, Borrelia-specific IgM AI may be important for sensitivity in early LNB.
Serious adverse events with novel beta-lactam/beta-lactamase inhibitor combinations: a large-scale pharmacovigilance analysisGatti, Milo; Raschi, Emanuel; De Ponti, Fabrizio
doi: 10.1007/s10096-020-04149-3pmid: 33415492
The purpose of this study is to characterize adverse events (AEs) of clinical interest reported with ceftolozane-tazobactam and ceftazidime-avibactam, as an aid in monitoring patients affected by severe multidrug-resistant Gram-negative infections. We queried the worldwide FDA Adverse Event Reporting System (FAERS) and performed disproportionality analysis, selecting only designated medical events (DMEs) where ceftolozane-tazobactam and ceftazidime-avibactam were reported as suspect. Serious neurological AEs were further investigated. The reporting odds ratios were calculated, deemed significant by the lower limit of the 95% confidence interval (LL95% CI) > 1. All other drugs/events recorded in FAERS and cephalosporins showing clinical evidence of neurological AEs were respectively selected as comparator for analysis of DMEs and neurotoxicity. Qualitative analysis including case-by-case assessment and deduplication was also performed. Overall, 654 and 506 reports mentioning respectively ceftolozane-tazobactam and ceftazidime-avibactam were found, with DMEs accounting respectively for 13.1% and 10.9% of cases. Agranulocytosis (N = 12; LL95% CI = 12.40) and pancytopenia (14; 6.18) emerged as unexpected AEs with ceftolozane-tazobactam, while acute pancreatitis (7; 8.63) was an over-reported unexpected DME with ceftazidime-avibactam. After deduplication, four unequivocally different cases of agranulocytosis with ceftolozane-tazobactam were retained, occurring on average after 8.8 days. Causality was probable and possible respectively in three and one case. Among neurological AEs exhibiting significant disproportionality, encephalopathy with both antibiotics and mental status changes with ceftazidime-avibactam were retained in at least three cases after deduplication. Although rare, clinicians should monitor high-risk patients (i.e. individuals affected by haematological malignances, HIV infection, or treated with concomitant myelotoxic agents) for early unexpected occurrence of agranulocytosis with ceftolozane-tazobactam.
Epidemiological, molecular, and clinical features of rotavirus infections among pediatrics in QatarMathew, Shilu; Al Ansari, Khalid; Al Thani, Asmaa A.; Zaraket, Hassan; Yassine, Hadi M.
doi: 10.1007/s10096-020-04108-ypmid: 33411172
Acute gastroenteritis (AGE) remains a major cause of diarrhea in developing and developed countries. Rotavirus (RV) is a leading cause of severe pediatric diarrhea worldwide. Here we report on the prevalence of circulating genotypes in association with demographics and clinical manifestations outcomes in Qatar. A total of 231 RV-positive fecal samples were collected from children suffering from AGE during 3 years study period between June 2016 and June 2019. The age of the subjects ranged between 2 months and 14 years (median of 16 months). The VP4 and VP7 were amplified and sequenced. Phylogenetic analyses were performed using MEGA7.0. Pearson’s chi-squared test was used to determine significant differences for comparisons of general categorical variables. RV infections were most common in children between 1 and 3 years of age (49%), followed by those < 1 year and > 3 years of age (33% and 28%, respectively). RV infections were more frequent in males than females, with a ratio of 1.4:1. RV infections occurred throughout the year, with a noticeable increase in summer (42.8%) and a drop in winter (20.1%). RV genotypes G3P[8] (30.8%), G2P[8] (12.3%), G4P[8] (11.7%), and G1P[8] (10.4%) were the common genotypes during the study period. The G3P[8] strain detected in our study revealed similarities to the equine-like G3P[8] (10.3%; 24/231) (KT988229.1), Wa-like genomic constellation (9%; 21/231) (MF563894.1), and DS-1-like strains (6.4%; 15/231) (LC386081.1). Based on the Vesikari score system, severe clinical illness including diarrhea and vomiting (average frequency: 4 to 5 times/day) was recorded for G3P[8] group, followed by G9P[8], G4P[8], and G1P[8]. Higher incidence for G3P[8], G2P[8], G4P[8], and G1P[8] were reported in Qatari subjects compared to other nationalities. The multinational status of a small country explains the wide diversity of circulating RV genotypes in Qatar. The highest prevalence and severe illnesses were recorded to G3P[8], which is different from other surrounding countries/global levels.