Transvenous extraction of permanent pacemaker and defibrillator leads: Reduced procedural complexity and higher procedural success rates in patients with infective versus noninfective indications.

INTRODUCTION: Transvenous lead extraction (TLE) is critical in the long-term management of patients with cardiac implanted electronic devices (CIEDs). The aim of the study is to evaluate the outcomes of TLE and to investigate the impact of infection. METHODS AND RESULTS: Data of patients undergoing extraction of permanent pacemaker and defibrillator leads during October 2014-September 2019 were prospectively analyzed. Overall, 242 consecutive patients (aged 71.0 ± 14.0 years, 31.4% female), underwent an equal number of TLE operations for the removal of 516 leads. Infection was the commonest indication (n = 201, 83.1%). Mean implant-to-extraction duration was 7.6 ± 5.4 years. Complete procedural success was recorded in 96.1%, and clinical procedural success was achieved in 97.1% of attempted lead extractions. Major complications occurred in two (0.8%) and minor complications in seven (2.9%) patients. Leads were removed exclusively by using locking stylets in 65.7% of the cases. In the subgroup of noninfective patients, advanced extraction tools were more frequently required compared to patients with CIED infections, to extract leads (success only with locking stylet: 55.8% vs. 67.8%, p = .032). In addition, patients without infection demonstrated lower complete procedural success rates (90.7% vs. 97.2%, p = .004), higher major complication rates (2.4% vs. 0.5%, p = .31) and longer procedural times (136 ± 13 vs. 111 ± 15 min, p = .001). CONCLUSIONS: Our data demonstrate high procedural efficacy and safety and indicate that in patients with noninfective indications, the procedure is more demanding, thus supporting the hypothesis that leads infection dissolves and/or prohibits the formation of fibrotic adherences.

Late Ebola virus relapse causing meningoencephalitis: a case report.

BACKGROUND: There are thousands of survivors of the 2014 Ebola outbreak in west Africa. Ebola virus can persist in survivors for months in immune-privileged sites; however, viral relapse causing life-threatening and potentially transmissible disease has not been described. We report a case of late relapse in a patient who had been treated for severe Ebola virus disease with high viral load (peak cycle threshold value 13.2). METHODS: A 39-year-old female nurse from Scotland, who had assisted the humanitarian effort in Sierra Leone, had received intensive supportive treatment and experimental antiviral therapies, and had been discharged with undetectable Ebola virus RNA in peripheral blood. The patient was readmitted to hospital 9 months after discharge with symptoms of acute meningitis, and was found to have Ebola virus in cerebrospinal fluid (CSF). She was treated with supportive therapy and experimental antiviral drug GS-5734 (Gilead Sciences, San Francisco, Foster City, CA, USA). We monitored Ebola virus RNA in CSF and plasma, and sequenced the viral genome using an unbiased metagenomic approach. FINDINGS: On admission, reverse transcriptase PCR identified Ebola virus RNA at a higher level in CSF (cycle threshold value 23.7) than plasma (31.3); infectious virus was only recovered from CSF. The patient developed progressive meningoencephalitis with cranial neuropathies and radiculopathy. Clinical recovery was associated with addition of high-dose corticosteroids during GS-5734 treatment. CSF Ebola virus RNA slowly declined and was undetectable following 14 days of treatment with GS-5734. Sequencing of plasma and CSF viral genome revealed only two non-coding changes compared with the original infecting virus. INTERPRETATION: Our report shows that previously unanticipated, late, severe relapses of Ebola virus can occur, in this case in the CNS. This finding fundamentally redefines what is known about the natural history of Ebola virus infection. Vigilance should be maintained in the thousands of Ebola survivors for cases of relapsed infection. The potential for these cases to initiate new transmission chains is a serious public health concern. FUNDING: Royal Free London NHS Foundation Trust.

Deaths attributable to carbapenem-resistant Enterobacteriaceae infections.

We evaluated the number of deaths attributable to carbapenem-resistant Enterobacteriaceae by using studies from around the world published before April 9, 2012. Attributable death was defined as the difference in all-cause deaths between patients with carbapenem-resistant infections and those with carbapenem-susceptible infections. Online databases were searched, and data were qualitatively synthesized and pooled in a metaanalysis. Nine studies met inclusion criteria: 6 retrospective case-control studies, 2 retrospective cohort studies, and 1 prospective cohort study. Klebsiella pneumoniae was the causative pathogen in 8 studies; bacteremia was the only infection in 5 studies. We calculated that 26%-44% of deaths in 7 studies were attributable to carbapenem resistance, and in 2 studies, which included bacteremia and other infections, -3% and -4% of deaths were attributable to carbapenem resistance. Pooled outcomes showed that the number of deaths was significantly higher in patients with carbapenem-resistant infections and that the number of deaths attributable to carbapenem resistance is considerable.

Drug interactions between antiretrovirals and new or emerging direct-acting antivirals in HIV/hepatitis C virus coinfection.

PURPOSE OF REVIEW: We reviewed the pharmacokinetic interactions between direct-acting antivirals against hepatitis C virus (HCV) and antiretroviral agents. RECENT FINDINGS: Most relevant pharmacokinetic studies involve healthy individuals and refer to the already licensed HCV protease inhibitors, boceprevir and telaprevir. Data from a phase II clinical trial question the clinical relevance of the interactions between boceprevir and HIV protease inhibitors. The use of a higher dose of telaprevir appears to offset the effect of efavirenz on telaprevir metabolism according to another phase II trial. Boceprevir and particularly telaprevir substantially increase the exposure to maraviroc, similarly to other potent CYP3A4 inhibitors. Different dosages of faldaprevir and daclatasvir have been recommended to be used in combination with a boosted HIV protease inhibitor vs. an efavirenz-based antiretroviral regimen. HIV protease inhibitors appear to substantially increase the exposure to simeprevir. The interactions between sofosbuvir and most antiretroviral agents do not appear to be of clinical relevance or to require dosage modifications. SUMMARY: The drug-drug interaction studies for HCV direct-acting antivirals and antiretrovirals are important in determining the appropriate drug combinations and dosages. The clinical implications of these interactions need further assessment in different categories of patients, including those with cirrhosis.

Outbreak of OXA-48 carbapenemase-producing Klebsiella pneumoniae in Greece involving an ST11 clone.

OBJECTIVES: First detected in Enterobacteriaceae isolates in Turkey, the OXA-48 carbapenemase has gradually disseminated in the wider Mediterranean area and Europe. Despite reports from other European regions, until now no such isolates have been detected in Greece. We describe the characteristics of the first outbreak caused by OXA-48-producing Klebsiella pneumoniae in Greece. METHODS: From December 2011 to March 2012, 13 ertapenem-resistant K. pneumoniae isolates, which were positive by the modified Hodge test while remaining negative by phenotypic screening for metallo-ß-lactamase (MBL) and KPC production, were recovered from nine patients. Patient records were retrieved to access patterns of acquisition. Resistance genes were identified by PCR and sequencing. ompK35, ompK36 and the genetic environment of the bla(OXA-48) gene were investigated. Plasmid profiling, conjugation experiments, PFGE and multilocus sequence typing (MLST) were performed. RESULTS: All isolates harboured the bla(OXA-48) gene along with the bla(CTX-M-15) and bla(OXA-1) genes. The bla(OXA-48) gene was located on a self-transferable IncL/M-type plasmid of ~62 kb, which harboured no other resistance genes. IS1999 was located upstream of the bla(OXA-48) gene. Genetic disruptions of the ompK35 and ompK36 genes were not detected. The isolates belonged to a unique PFGE clone and MLST assigned them to sequence type ST11. All cases were characterized as hospital acquired and none of them was linked to immigration or history of travel in endemic areas. CONCLUSIONS: Carbapenem resistance due to MBL and KPC carbapenemases is currently on an endemic scale in Greece and this report highlights the wider undetected dissemination of yet another carbapenemase in this region.

Incidence, clinical, microbiological features and outcome of bloodstream infections in patients undergoing hemodialysis.

OBJECTIVES: Infection is a common cause of death among hemodialysis patients. The study investigated incidence, risk factors, clinical features and outcome of bloodstream infections (BSIs) in haemodialysis patients. METHODS: The records of haemodialysis patients from 1999 to 2005 were reviewed. Risk factors were investigated by multivariate analysis. RESULTS: There were identified 148 bacteremic episodes, in 102 patients. The BSI rate was 0.52 per 1000 patient-days. Of the 148 episodes, 34 occurred in patients with permanent fistulae (0.18/1000 patient-days); 19 in patients with grafts (0.39/1000 patient-days); 28 in patients with permanent tunneled central catheters (1.03/1000 patient-days); and 67 in those with temporary-catheter (3.18/1000 patient-days). With fistula as reference, the BSI ratio was 1.84 with arteriovenous graft (P=.029), 4.85 with permanent central venous catheter (P<.001), and 14.88 with temporary catheter (P <.001). Catheter related were 41 episodes (28%). Gram positive organism were responsible for 96 episodes (65%), with S. aureus ( 55%) the most frequent, followed by S. epidermidis (26%) and Gram-negative for 36 (23%), with E. coli (39%) the most frequent. Infection was polymicrobial in 14 (9.5%). Diabetes (p<0.001), low serum albumin (p=0.040) and low hemoglobin (p<0.001) were significant risk factors. During hospitalization 18 patients (18%) died. Septic shock (p<0.001) and polymicrobial infection (p=0.041) were associated with in-hospital mortality. CONCLUSION: The risk of BSI in patients undergoing hemodialysis is related to the catheter type and vascular access. Septic shock and polymicrobial infection predispose to unfavourable outcome.

Severe sepsis and septic shock due to Plasmodium vivax infection.

Plasmodium vivax malaria is typically characterized by a mild and benign clinical course. Organ dysfunction is rarely seen, whereas acute lung injury has been found to occur after starting antimalarial treatment. We present an unusual case of severe sepsis and septic shock due to Plasmodium vivax monoinfection.

In vitro antimicrobial susceptibility to isepamicin of 6,296 Enterobacteriaceae clinical isolates collected at a tertiary care university hospital in Greece.

The reevaluation of "forgotten" antibiotics can identify new therapeutic options against extensively drug-resistant Gram-negative pathogens. We sought to investigate isepamicin in this regard. We retrospectively evaluated the antimicrobial susceptibility to isepamicin of Enterobacteriaceae sp. isolates from unique patients, collected at the microbiological laboratory of the University Hospital of Heraklion, Crete, Greece, from 2004 to 2009. Susceptibility testing was done with the automated Vitek 2 system. The breakpoints for susceptibility to isepamicin, tigecycline, and other antibiotics were those proposed by the Comité de l'Antibiogramme de la Société Française de Microbiologie (CA-SFM), the FDA, and the CLSI, respectively. A total of 6,296 isolates were studied, including primarily 3,401 (54.0%) Escherichia coli, 1,040 (16.5%) Klebsiella pneumoniae, 590 (9.4%) Proteus mirabilis, and 460 (7.3%) Enterobacter sp. isolates. Excluding the species with intrinsic resistance to each antibiotic, antimicrobial susceptibility was highest for colistin (5,275/5,441 isolates [96.9%]) and isepamicin (6,103/6,296 [96.9%]), followed by meropenem (5,890/6,296 [93.6%]), imipenem (5,874/6,296 [93.3%]), and amikacin (5,492/6,296 [87.2%]). The antimicrobial susceptibility of the 1,040 K. pneumoniae isolates was highest for isepamicin (95.3%), followed by colistin (89.3%) and meropenem (63.0%). Regarding resistant K. pneumoniae isolates, susceptibility to isepamicin was observed for 91.1% of the 392, 87.7% of the 375, and 85.6% of the 111 isolates that were nonsusceptible to the carbapenems, all other aminoglycosides, and colistin, respectively. Isepamicin exhibited high in vitro activity against almost all of the Enterobacteriaceae species. It could particularly serve as a last-resort therapeutic option for carbapenem-resistant K. pneumoniae in our region, where it is endemic, as it does not show considerable cross-resistance with other aminoglycosides.

Fosfomycin: evaluation of the published evidence on the emergence of antimicrobial resistance in Gram-negative pathogens.

Fosfomycin has attracted renewed interest for the treatment of lower urinary tract and even systemic infections caused by Gram-negative pathogens with resistance to traditionally used agents. The main concern regarding the clinical utility of fosfomycin refers to the potential for the emergence of resistance during therapy. In this review, we evaluate the available published evidence regarding the mechanisms and the frequency of in vitro mutational resistance to fosfomycin in Gram-negative pathogens. We also review data regarding the emergence of resistance in clinical studies of fosfomycin therapy in various infectious syndromes and data from studies that evaluate the evolution of fosfomycin resistance over time. There appears to be discordance between the high frequency of mutational resistance to fosfomycin in vitro and the lower extent of this phenomenon in clinical studies. This discordance could at least partly be attributed to a biological cost associated with common mutations that confer resistance to fosfomycin, including decreased growth rate and low adherence to epithelial cells for the resistant mutants. The development of resistance appears to be more frequent both in vitro and in clinical studies for Pseudomonas aeruginosa in comparison with Escherichia coli, whereas relevant data for other Enterobacteriaceae are relatively scarce. The urinary tract seems to provide a favourable environment for the use of fosfomycin with a low associated likelihood for the emergence of resistance, owing to high drug concentrations and acidic pH. Additional data are needed to further clarify the optimal use of fosfomycin for different infectious syndromes caused by contemporary multidrug-resistant pathogens.

ß-D-glucan assay for the diagnosis of invasive fungal infections: a meta-analysis.

We aimed to assess the accuracy of measuring serum or plasma (1→3)-ß-D-glucan (BDG) for the diagnosis of invasive fungal infections (IFIs) by means of a meta-analysis of relevant studies. We searched in bibliographic databases for relevant cohort or case-control studies. We primarily compared BDG between patients with proven or probable IFIs (excluding Pneumocystis jirovecii infections), according to the criteria of the European Organization for Research and Treatment of Cancer/Mycoses Study Group or similar criteria, and patients without IFIs (excluding healthy individuals as controls). A total of 2979 patients (594 with proven or probable IFIs), included in 16 studies, were analyzed. The pooled sensitivity of BDG was 76.8% (95% confidence interval [CI], 67.1%-84.3%), and the specificity was 85.3% (95% CI, 79.6%-89.7%). The area under the summary receiver operating characteristic curve was 0.89. Marked statistical heterogeneity was noted. BDG has good diagnostic accuracy for distinguishing proven or probable IFIs from no IFIs. It can be useful in clinical practice, if implemented in the proper setting and interpreted after consideration of its limitations.

Inadequate statistical power of published comparative cohort studies on ventilator-associated pneumonia to detect mortality differences.

BACKGROUND: Comparative cohort studies are often conducted to identify novel therapeutic strategies or prognostic factors for ventilator-associated pneumonia (VAP). We aimed to evaluate the power of such studies to provide clinically and statistically significant conclusions with regard to mortality differences. METHODS: We searched in PubMed and Scopus for comparative cohort studies that evaluated mortality in patients with VAP. We calculated the central estimates and corresponding 95% confidence intervals (CIs) for mortality differences between compared patient groups. We also calculated the statistical power of the included studies to detect a difference in mortality that corresponds to a risk ratio of 0.80. RESULTS: We identified 39 (20 prospective) comparative cohort studies on VAP as eligible for inclusion in this analysis. The median absolute risk difference in mortality between compared groups was 10% (interquartile range [IQR], 5%-18%), and the median width of the 95% CI of the absolute risk difference in mortality was 34% (IQR, 28%-42.5%). The median power of the included studies to detect a risk ratio for mortality of 0.80 was 14.7% (IQR, 10.6%-21.8%). CONCLUSIONS: There is considerable uncertainty around the central estimate of comparative cohort studies on VAP with regard to mortality differences. For a wiser use of resources allocated to research, we emphasize the need to conduct cohort studies with larger sample size so that potential differences between the compared groups are more likely to be shown.

Emerging Treatment Options for Infections by Multidrug-Resistant Gram-Positive Microorganisms.

Antimicrobial agents are currently the mainstay of treatment for bacterial infections worldwide. However, due to the increased use of antimicrobials in both human and animal medicine, pathogens have now evolved to possess high levels of multi-drug resistance, leading to the persistence and spread of difficult-to-treat infections. Several current antibacterial agents active against Gram-positive bacteria will be rendered useless in the face of increasing resistance rates. There are several emerging antibiotics under development, some of which have been shown to be more effective with an improved safety profile than current treatment regimens against Gram-positive bacteria. We will extensively discuss these antibiotics under clinical development (phase I-III clinical trials) to combat Gram-positive bacteria, such as Staphylococcus aureus, Enterococcus faecium and Streptococcus pneumoniae. We will delve into the mechanism of actions, microbiological spectrum, and, where available, the pharmacokinetics, safety profile, and efficacy of these drugs, aiming to provide a comprehensive review to the involved stakeholders.

Short epidemiological overview of the current situation on COVID-19 pandemic in Southeast European (SEE) countries.

We are living in times where a viral disease has brought normal life in much of the world to a halt. The novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) started in December 2019 in Wuhan, China initially and in a short time crossed the European borders. After mitigating the epidemic in China, Italy became one of the most COVID-19 affected countries worldwide. International travelers are important sources of infectious diseases and a possible source of epidemic. Due to its political, geographic, and cultural similarities, Italy is one of the main economic partners of Southeast European (SEE) countries. Our data show that infection in index cases in all 11 SEE countries was travel-related with Italy being a source country for 8/11 countries. After the first case identifications on February 25, the number of cases in SEE countries is continually rising reaching the total number of 15,612 with 565 fatal cases and overall case fatality ratio (CFR) of 3.6 (median 3.8, range 0.8-5.5) by April 10, 2020. At a time when the COVID-19 pandemic is approaching its peak, apart from the problems with treatment of the disease and care for critically ill patients, there are other equally important problems, such as organization of outbreak response, provision of health care, lack of hospital personnel, disruption of personal protective equipment supply chains and health care workers (HCWs) protection. But what is more important is the heroic behavior of the HCWs who are showing their humanity by disregarding their lives.

Clinical significance of the pharmacokinetic and pharmacodynamic characteristics of tigecycline.

Tigecycline is a novel antibacterial agent with a wide spectrum of antimicrobial activity that includes pathogens with clinically significant resistance patterns. The clinical effectiveness of tigecycline has been evaluated in several non-inferiority, phase III, randomized, double-blind, controlled clinical trials regarding, mainly, complicated skin and skin structure infections and complicated intra-abdominal infections. Clinical data regarding the effectiveness of tigecycline against infections caused by multidrug-resistant pathogens that commonly affect severely ill patients as well as community acquired pneumonia are favorable, yet limited. The consideration of the pharmacokinetic and pharmacodynamic properties of tigecycline may aid in further understanding the therapeutic role of this agent. Respectively, the utility of tigecycline in the treatment of severe infections involving the bloodstream has not been substantiated, particularly regarding pathogens with borderline susceptibility. Moreover, the fact that a relatively small proportion of the administered tigecycline dose is excreted unchanged in the urine may compromise the effectiveness of this agent in serious urinary tract infections. Increasing the dose of tigecycline to maximize effectiveness against severe infections appears as an appealing therapeutic option, considering the linear pharmacokinetics exhibited by this agent. However, gastrointestinal toxicity (nausea and vomiting) is usually dose-limiting. Further research is recommended on therapeutic strategies to optimize the effectiveness and safety of tigecycline therapy in severely ill patients.

Antibiotics versus placebo or watchful waiting for acute otitis media: a meta-analysis of randomized controlled trials.

BACKGROUND: Recommendations on withholding antibiotics in children with acute otitis media (AOM) have been inadequately implemented in clinical practice. OBJECTIVES: We evaluated the role of prescribing antibiotics for AOM. METHODS: We performed a meta-analysis of randomized controlled trials (RCTs) that were retrieved from searches performed in the PubMed and Cochrane databases, and compared antibiotic treatment with placebo or watchful waiting (delayed antibiotic treatment if clinically indicated) for patients with AOM. RESULTS: We identified seven trials comparing antibiotic treatment with placebo (all double-blinded) and four trials comparing antibiotic treatment with watchful waiting (two investigator-blinded and two open-label) trials, all of which involved children (6 months to 12 years). Clinical success was more likely with antibiotics than comparator treatment in: placebo-controlled trials [seven RCTs, 1405 patients, risk ratio (RR) = 1.11, 95% confidence interval (CI) = 1.05-1.18]; watchful waiting trials (four RCTs, 915 patients, RR = 1.18, 95% CI = 1.07-1.32); and all trials combined (11 RCTs, 2320 patients, RR = 1.13, 95% CI = 1.08-1.19). Similarly, persistence of symptoms 2-4 days after treatment initiation was less likely with antibiotics in: placebo-controlled trials (four RCTs, 1014 patients, RR = 0.75, 95% CI = 0.64-0.88) and all trials combined (five RCTs, 1299 patients, RR = 0.68, 95% CI = 0.54-0.85). Diarrhoea was more likely with antibiotics (seven RCTs, 1807 patients, RR = 1.50, 95% CI = 1.16-1.95). No differences between the compared treatments were found regarding other effectiveness and safety outcomes. CONCLUSIONS: Antibiotic treatment is associated with a more favourable clinical course in children with AOM, compared with placebo, and also compared with watchful waiting. However, safety issues and the rather small treatment effect difference render the consideration of additional factors necessary in relevant clinical decision making.

Serum procalcitonin for prediction of renal parenchymal involvement in children with urinary tract infections: a meta-analysis of prospective clinical studies.

OBJECTIVE: To determine by meta-analysis whether serum procalcitonin (PCT) is a useful marker of acute renal parenchymal involvement (RPI) in children with culture-proven urinary tract infection (UTI), as diagnosed by acute-phase DMSA (Tc-99m dimercaptosuccinic acid) renal scintigraphy. STUDY DESIGN: We searched PubMed and the Cochrane Central Register of Controlled Trials for prospective studies involving children with culture-proven UTIs. Additional eligibility criteria were measurement of serum PCT at presentation and performance of DMSA scintigraphy within 14 days. RESULTS: Overall, 10 studies eligible for inclusion, involving a total of 627 children, were identified. Half of these studies evaluated children with a first episode of UTI; 8 involved children with febrile UTIs. Using a cutoff value of 0.5 to 0.6 ng/mL, the pooled diagnostic odds ratio of serum PCT for UTI with RPI was 14.25 (95% confidence interval, 4.70 to 43.23). High statistical between-study heterogeneity that could mainly be attributed to 2 studies was observed. The remaining 8 studies uniformly favored PCT use. CONCLUSIONS: In children with culture-proven UTI, a serum PCT value >0.5 ng/mL predicts reasonably well the presence of RPI, as evidenced by DMSA scintigraphy. PCT may aid in the identification of children with UTI, necessitating more intense evaluation and management.

Comparison of SCImago journal rank indicator with journal impact factor.

The application of currently available sophisticated algorithms of citation analysis allows for the incorporation of the "quality" of citations in the evaluation of scientific journals. We sought to compare the newly introduced SCImago journal rank (SJR) indicator with the journal impact factor (IF). We retrieved relevant information from the official Web sites hosting the above indices and their source databases. The SJR indicator is an open-access resource, while the journal IF requires paid subscription. The SJR indicator (based on Scopus data) lists considerably more journal titles published in a wider variety of countries and languages, than the journal IF (based on Web of Science data). Both indices divide citations to a journal by articles of the journal, during a specific time period. However, contrary to the journal IF, the SJR indicator attributes different weight to citations depending on the "prestige" of the citing journal without the influence of journal self-citations; prestige is estimated with the application of the PageRank algorithm in the network of journals. In addition, the SJR indicator includes the total number of documents of a journal in the denominator of the relevant calculation, whereas the journal IF includes only "citable" articles (mainly original articles and reviews). A 3-yr period is analyzed in both indices but with the use of different approaches. Regarding the top 100 journals in the 2006 journal IF ranking order, the median absolute change in their ranking position with the use of the SJR indicator is 32 (1st quartile: 12; 3rd quartile: 75). Although further validation is warranted, the novel SJR indicator poses as a serious alternative to the well-established journal IF, mainly due to its open-access nature, larger source database, and assessment of the quality of citations.

Effectiveness and safety of short vs. long duration of antibiotic therapy for acute bacterial sinusitis: a meta-analysis of randomized trials.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Treatment guidelines generally support that a 10-14-day antibiotic regimen should be administered to uncomplicated acute bacterial sinusitis patients. However, the level of evidence for such a recommendation is rather weak. Treatment of such duration may have disadvantages compared with a shorter duration but equally effective regimen, including the promotion of bacterial drug resistance, poorest patient compliance, higher toxicity, and a greater overall economic burden. WHAT THIS STUDY ADDS: The findings of this meta-analysis suggest that short-course antibiotic treatment has similar effectiveness to longer-course treatment for patients with acute uncomplicated bacterial sinusitis, when treatment is warranted. However, we should underscore the importance of the clinician's own assessment, so that antimicrobial therapy should not inappropriately be curtailed in a patient not adequately responding to the regimen administered. We sought to evaluate the effectiveness and safety of short-course antibiotic treatment for acute bacterial sinusitis (ABS) compared with longer duration treatment. We performed a meta-analysis of randomized controlled trials (RCTs), identified by searching PubMed and the Cochrane Central Register of Controlled Trials. We included RCTs that compared short-course (up to 7 days) vs. long-course therapy (> or =2 days longer than short-course), with the same antimicrobial agent, in the same daily dosage, for patients with ABS. Twelve RCTs (10 double-blinded) involving adult patients with radiologically confirmed ABS were included. There was no difference in the comparison of short-course (3-7 days) with long-course treatment (6-10 days) regarding clinical success [12 RCTs, 4430 patients, fixed effect model (FEM), odds ratio (OR) 0.95, 95% confidence interval (CI) 0.81, 1.12]; microbiological efficacy; relapses; adverse events (10 RCTs, 4172 patients, random effects model, OR 0.88, 95% CI 0.71, 1.09); or withdrawals due to adverse events. In the sensitivity analysis comparing 5- vs. 10-day regimens, clinical success was similar, although adverse events were fewer with short-course treatment (5 RCTs, 2151 patients, FEM, OR 0.79, 95% CI 0.63, 0.98). Although antibiotics for acute sinusitis should be reserved for select patients with substantial probability of bacterial disease, accurate clinical diagnosis is often difficult to attain. Short-course antibiotic treatment had comparable effectiveness to a longer course of therapy for ABS. Shortened treatment, particularly for patients without severe disease and complicating factors, might lead to fewer adverse events, better patient compliance, lower rates of resistance development and fewer costs.

Seasonality of mortality: the September phenomenon in Mediterranean countries.

BACKGROUND: Seasonal increases in the mortality rate have been associated with excessively cold or hot weather. We evaluated monthly patterns of mortality in selected countries. METHODS: We analyzed all-cause mortality statistics from 5 European Mediterranean countries (Cyprus, France, Greece, Italy, Spain), Sweden, North America (United States and Canada), Australia, New Zealand and Japan. We extracted and tabulated data on monthly all-cause mortality in the general population from the earliest to the latest year that records were available. RESULTS: We identified relevant data for a period of 2-57 years in each country. In the Mediterranean countries, the lowest average daily mortality was observed in September (all countries, 125/168 [74%] years). The fewest deaths were in August in Sweden (14/20 [70%] years) and North America (32/50 [64%] years). The fewest deaths in Japan occurred in July (2/2 [100%] years). In the southern hemisphere, the lowest mortality in Australia occurred in March (7/10 [70%] years) and in February for New Zealand (cumulative over 24 years). INTERPRETATION: Mortality in the general population declines in the late summer to early fall months in the countries evaluated. Environmental parameters may partly account for these associations, and further research is needed on the contribution of additional factors such as summer vacations.

Comparison of adverse events between oral and intravenous formulations of antimicrobial agents: a systematic review of the evidence from randomized trials.

BACKGROUND: Some clinicians may favor a strategy of early switch to oral antimicrobial therapy for patients responding to initial intravenous therapy. An important relevant consideration refers to the comparative safety and tolerability between oral and intravenous antimicrobial therapy. LITERATURE SEARCH/STUDY SELECTION: We sought to evaluate the above-mentioned issue by performing a systematic review of randomized studies comparing the occurrence of adverse events between oral and intravenous antimicrobial therapy with the same agents. FINDINGS: Ten relevant studies (five randomized controlled trials, three randomized cross-over studies, and two randomized, placebo-controlled, parallel-design studies) were included. Seven of the studies evaluated antibacterials (fluoroquinolones in four, and telithromycin, amoxicillin-clavulanic acid, and linezolid in one study each, respectively), whereas two studies evaluated ganciclovir, and one evaluated isavuconazole. No difference was observed in the rate of total adverse events between oral and intravenous administration of the same antimicrobial agents in any of the included studies that reported specific relevant data. Injection site reactions were noted more frequently with intravenous treatment in one study. No serious drug-related adverse events were reported, while study withdrawals due to adverse events did not considerably differ between the compared groups in any of the included studies. CONCLUSION: There are only limited comparative data regarding the adverse events associated with the administration of the same antimicrobial agents by the oral and intravenous route. Our review indicates that the adverse event profile of oral and intravenous antimicrobial therapy does not differ considerably; however, this issue requires validation by further studies.