actual role of older oral antibiotics in the treatment of resistant urinary tract infections utis

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Clinical evaluation of guidelines and therapeutic approaches in multi drug-resistant urinary tract infections

Antibiotic resistance represents a real health emergency worldwide, mostly due to the lack of new antibiotics active against multidrug-resistant Enterobacteriaceae. Considering the global epidemiological situation in several infections, including urinary tract infections (UTIs), some antibiotics, such as fluoroquinolones and trimethoprim/sulphamethoxazole, can no longer be used for empiric treatment due to high resistance rates. However, some old antibiotics maintain high microbiological activity against UTI pathogens: according to many recent guidelines, fosfomycin trometamol, nitrofurantoin and pivmecillinam are recommended for the first-line treatment of uncomplicated UTIs. This article provides an overview of the therapeutic management of UTIs, especially uncomplicated and recurrent cystitis, as well as complicated UTIs such as catheter-related UTIs, and UTIs in males, post-menopausal women and diabetic patients, based on the main international guidelines

New antibiotic development: barriers and opportunities

Antibiotic resistance represents a serious threat to public health worldwide, leading to increased healthcare costs, prolonged hospital stays, treatment failures and deaths. To address the emergency of multidrug-resistance, the major international societies of infectious diseases and public health have developed strategies and guidelines to reduce unnecessary antimicrobial use as well as to incite the development of new antibiotics targeting multidrug-resistant pathogens. Even though pharmaceutical companies have been developing new antibiotics since 2010, the global situation is still worrisome. Indeed, the currently available data regarding new antibiotics are limited to microbiological activity and pharmacokinetic profile and their use for the treatment of life-threatening infections (i.e., sepsis) is often off-label. The aim of this article is to present the antibiotic molecules recently commercialized and with which clinicians will deal quite often in next years. We describe ceftolozane/tazobactam, ceftazidime/avibactam, eravacycline, plazomicin, dalbavancin, oritavancin and tedizolid in terms of mechanism of action, antimicrobial spectrum, trials behind the approval and possible indications for the future. In last few years, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved many new antibiotic molecules but, unfortunately, they lack in biological innovation and in wide clinical indications. These agents show appealing properties for off-label use, as we propose in the article, but caution is still needed considering that high-quality clinical data are limited

Performance of alere determine HIV-1/2 Ag/Ab combo rapid test for acute HIV infection: A case report | Performance del test rapido Alere Determine HIV-1/2 Ag/Ab Combo nell?infezione acuta da HIV: Un caso clinic

We describe a case of symptomatic acute HIV infection in a young man where a fourth-generation rapid screening test combining HIV-specific antibody and p24 antigen was negative. In highly suspicious cases of acute HIV infection, plasma HIV RNA assays together with conventional, non-rapid screening tests should be used

Clinical Features, Short-Term Mortality, and Prognostic Risk Factors of Septic Patients Admitted to Internal Medicine Units: Results of an Italian Multicenter Prospective Study

Only a few studies provided data on the clinical history of sepsis within internal Medicine units.The aim of the study was to assess the short-term mortality and to evaluate the prognostic risk factors in a large cohort of septic patients treated in internal medicine units.Thirty-one internal medicine units participated to the study. Within each participating unit, all admitted patients were screened for the presence of sepsis.A total of 533 patients were included; 78 patients (14.6%, 95%CI 11.9, 18.0%) died during hospitalization; mortality rate was 5.5% (95% CI 3.1, 9.6%) in patients with nonsevere sepsis and 20.1% (95%CI 16.2, 28.8%) in patients with severe sepsis or septic shock. Severe sepsis or septic shock (OR 4.41, 95%CI 1.93, 10.05), immune system weakening (OR 2.10, 95%CI 1.12, 3.94), active solid cancer (OR 2.14, 95% CI 1.16, 3.94), and age (OR 1.03 per year, 95% CI 1.01, 1.06) were significantly associated with an increased mortality risk, whereas blood culture positive for Escherichia coli was significantly associated with a reduced mortality risk (OR 0.46, 95%CI 0.24, 0.88).In-hospital mortality of septic patients treated in internal medicine units appeared similar to the mortality rate obtained in recent studies conducted in the ICU setting

CFTR Modulation Reduces SARS-CoV-2 Infection in Human Bronchial Epithelial Cells

People with cystic fibrosis should be considered at increased risk of developing severe symptoms of COVID-19. Strikingly, a broad array of evidence shows reduced spread of SARS-CoV-2 in these subjects, suggesting a potential role for CFTR in the regulation of SARS-CoV-2 infection/replication. Here, we analyzed SARS-CoV-2 replication in wild-type and CFTR-modified human bronchial epithelial cell lines and primary cells to investigate SARS-CoV-2 infection in people with cystic fibrosis. Both immortalized and primary human bronchial epithelial cells expressing wt or F508del-CFTR along with CRISPR/Cas9 CFTR-ablated clones were infected with SARS-CoV-2 and samples were harvested before and from 24 to 72 h post-infection. CFTR function was also inhibited in wt-CFTR cells with the CFTR-specific inhibitor IOWH-032 and partially restored in F508del-CFTR cells with a combination of CFTR modulators (VX-661+VX-445). Viral load was evaluated by real-time RT-PCR in both supernatant and cell extracts, and ACE-2 expression was analyzed by both western blotting and flow cytometry. SARS-CoV-2 replication was reduced in CFTR-modified bronchial cells compared with wild-type cell lines. No major difference in ACE-2 expression was detected before infection between wild-type and CFTR-modified cells, while a higher expression in wild-type compared to CFTR-modified cells was detectable at 72 h post-infection. Furthermore, inhibition of CFTR channel function elicited significant inhibition of viral replication in cells with wt-CFTR, and correction of CFTR function in F508del-CFTR cells increased the release of SARS-CoV-2 viral particles. Our study provides evidence that CFTR expression/function is involved in the regulation of SARS-CoV-2 replication, thus providing novel insights into the role of CFTR in SARS-CoV-2 infection and the development of therapeutic strategies for COVID-19

Consensus document on controversial issues in the treatment of complicated skin and skin-structure infections

Summary Background Complicated skin and skin-structure infections (cSSSI), including surgical site infections (SSI), cellulitis, and abscesses, have been extensively studied, but controversial issues still exist. Controversial issues The aim of this GISIG (Gruppo Italiano di Studio sulle Infezioni Gravi) working group – a panel of multidisciplinary experts – was to define recommendations for the following controversial issues: (1) What is the efficacy of topical negative pressure wound treatment as compared to standard of care in the treatment of severe surgical site infections, i.e., deep infections, caused by Gram-positive microorganisms? (2) Which are the most effective antibiotic therapies in the treatment of cSSSI, including SSI, due to methicillin-resistant staphylococci? Results are presented and discussed. Methods A systematic literature search using the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and www.clinicaltrials.gov databases of randomized controlled trials and/or non-randomized studies was performed. A matrix was created to extract evidence from original studies using the CONSORT method to evaluate randomized clinical trials and the Newcastle–Ottawa Quality Assessment Scale for case–control studies, longitudinal cohorts, and retrospective studies. The GRADE method was used for grading quality of evidence. An analysis of the studies published between 1990 and 2008 is presented and discussed in detail

Therapeutic Value and Innovation of a Drug and Criteria for Evaluation: A Multidisciplinary Experience in the Veneto Region

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Aetiology and antibiotic resistance issues regarding urological procedures

There are specific indications in urological procedures [transurethral resection of the prostate (TURP), transurethral resection of the bladder (TURB), endoscopic procedures, and all interventions classified as contaminated or dirty] requiring antibiotic prophylaxis. Most postoperative infections are caused by enterococci of the Gram-positive strains and Enterobacteriaceae of the Gram-negative ones. As reported by the European Center for Disease Prevention and Control (ECDC), there are increasing numbers of antibiotic-resistant pathogens. Most Enterococcus faecium strains are ampicillin-resistant and the Enterobacteriaceae have a high prevalence of extended-spectrum beta-lactamase (ESBL) producers, for which the cephalosporins and penicillins are not drugs of choice. In recent years, there are also increasing numbers of Gram-negative strains that are able to produce carbapenemases and for which the only therapeutic options are gentamicin, tigecycline and colistin. An alternative to these drugs, from a prophylactic point of view, is fosfomycin, an old antibiotic that maintains bactericidal activity against both enterococci and multidrug-resistant Enterobacteriaceae. Available in an oral formulation as trometamol salt, fosfomycin reaches high plasma and urine concentrations, and is therefore a possible alternative to other drugs both for therapy and urological prophylaxis

Terapia empirica delle infezioni batteriche. Profilassi antibiotica in medicina e chirurgia

Negli ultimi anni si \ue8 assistito, nell\u2019ambito della terapia antinfettiva, a un costante incremento delle resistenze sia nella patologia di comunit\ue0 che, soprattutto, nei reparti ospedalieri.Anche nelle lungodegenze per anziani si ritrovano, con frequenza crescente, batteri multi resistenti. A fronte di questa evoluzione delle resistenze si riscontra un netto decremento nella ricerca e nella commercializzazione di nuovi antibiotici.E\u2019 quindi fondamentale che i medici utilizzino al meglio i vecchi e i pochi nuovi farmaci sia in terapia che in profilassi. La terapia antibiotica, sia essa empirica o mirata, deve essere basata su dati microbiologici, farmacologici e clinici.Le recenti conoscenze di farmacocinetica e farmacodinamica hanno consentito di ottimizzare la posologia e il ritmo di somministrazione degli antibiotici.Non si devono dimenticare, nel contesto dei criteri di scelta, le conoscenze di farmaco economia, nonch\ue9 l\u2019impatto degli antibiotici sulla ecologia dell\u2019ospedale.Il testo che abbiamo approntato rappresenta una revisione della terapia empirica e della profilassi antibiotica ed \ue8 rivolto sia ai medici che operano sul territorio che a quelli che lavorano in ospedale