Short Cycle, Intermittent Therapy: A Valuable Option in Selected, Virologically Suppressed People Living with HIV.

The use of long-acting antiretroviral regimens will not be suitable for all people living with HIV for various reasons (previous virological failure with drugs of the same class, side effects, logistic difficulties, and costs). We think that short-cycle therapies could represent a feasible and valuable option for antiretroviral treatment optimization in selected individuals. So here we review clinical evidence about efficacy of short-cycle therapy in suppressed HIV-infected patients.

Short-cycle therapy in HIV-infected adults: rilpivirine combination 4 days on/3 days off therapy.

BACKGROUND: Short-cycle therapy (SCT) is the administration of ART for 4 or 5 consecutive days a week, followed by 3 or 2 days off therapy. Its benefits include improving patient satisfaction and reducing ART toxicity and costs. METHODS: In this observational study we included HIV-infected adults with a three-drug ART containing rilpivirine, a history of long-term virological suppression and no evidence of resistance to previous drug regimens. Patients switched to a SCT of 4 days on/3 days off and were followed for 48 weeks with regular check-ups. The primary outcome was virological suppression; secondary outcomes were changes in CD4+ cells and rilpivirine plasma concentration, the occurrence of adverse events and resistance in the case of failure, and patient satisfaction. RESULTS: At week 48 no virological failure was observed, with a virological suppression rate of 30/30 (100%). Three patients switched back to continuous therapy for other reasons, with an overall success rate of SCT of 30/33 (90.9%, 95% CI = 81.24% to 100%). The CD4+ mean value increased by +64 cells/mm3 (95% CI = -59 to +187 cells/mm3; P = 0.052). No adverse events were observed and the mean total score in the satisfaction questionnaire was 57.7/60 (96.22%). Rilpivirine plasma concentration was below the efficacy threshold in 71.3% of the samples, suggesting that the patients' characteristics, more than the drug's pharmacokinetics, played a role in maintaining virological suppression. CONCLUSIONS: SCT with rilpivirine-containing regimens could be an effective alternative to continuous therapy in selected HIV-infected patients with previous long-term virological suppression.

Lung Ultrasound Patterns and Clinical-Laboratory Correlates during COVID-19 Pneumonia: A Retrospective Study from North East Italy.

BACKGROUND AND AIM: Lung ultrasound (LUS) is a convenient imaging modality in the setting of coronavirus disease-19 (COVID-19) because it is easily available, can be performed bedside and repeated over time. We herein examined LUS patterns in relation to disease severity and disease stage among patients with COVID-19 pneumonia. METHODS: We performed a retrospective case series analysis of patients with confirmed SARS-CoV-2 infection who were admitted to the hospital because of pneumonia. We recorded history, clinical parameters and medications. LUS was performed and scored in a standardized fashion by experienced operators, with evaluation of up to 12 lung fields, reporting especially on B-lines and consolidations. RESULTS: We included 96 patients, 58.3% men, with a mean age of 65.9 years. Patients with a high-risk quick COVID-19 severity index (qCSI) were older and had worse outcomes, especially for the need for high-flow oxygen. B-lines and consolidations were located mainly in the lower posterior lung fields. LUS patterns for B-lines and consolidations were significantly worse in all lung fields among patients with high versus low qCSI. B-lines and consolidations were worse in the intermediate disease stage, from day 7 to 13 after onset of symptoms. While consolidations correlated more with inflammatory biomarkers, B-lines correlated more with end-organ damage, including extrapulmonary involvement. CONCLUSIONS: LUS patterns provide a comprehensive evaluation of patients with COVID-19 pneumonia that correlated with severity and dynamically reflect disease stage. LUS patterns may reflect different pathophysiological processes related to inflammation or tissue damage; consolidations may represent a more specific sign of localized disease, whereas B-lines seem to be also dependent upon generalized illness due to SARS-CoV-2 infection.

Effectiveness and Sustainability of an Antimicrobial Stewardship Program for Perioperative Prophylaxis in Pediatric Surgery.

Background-Appropriate perioperative antibiotic prophylaxis (PAP) is essential to prevent surgical site infections (SSIs) and to avoid antibiotics misuse. Aim-The aim of this study is to determine the effectiveness and long-term sustainability of an antimicrobial stewardship program (ASP), based on a clinical pathway (CP) and periodic education, to improve adherence to the guidelines for PAP in a tertiary care pediatric surgery center. Methods-We assessed the changes in PAP correctness and its effect on SSIs between the six months before and the 24 months after the implementation of ASP in the Pediatric Surgery Unit of the Department of Women's and Children's Health of Padova. The ASP was addressed to all surgeons and anesthesiologists of the Pediatric Surgery Unit. The primary outcome was appropriateness of PAP (agent, timing of the first dose, and duration). SSI rate was the secondary outcome. Results-1771 patients were included in the study and 676 received PAP. The overall correctness of the PAP, in terms of agent, timing, and duration, increased significantly after the CP implementation. What changed most was the PAP discontinuation within 24 h (p < 0.001). Cefazolin was the most used antibiotic, with a significant increase in the post-intervention period (p < 0.001) and with a reduction in the use of other broad-spectrum antibiotics. No variations in the incidence of SSIs were reported in the five periods (p = 0.958). Conclusion-The implementation of an ASP based on CP and education is an effective and sustainable antimicrobial stewardship tool for improving the correct use of PAP.

Variation of effect estimates in the analysis of mortality and length of hospital stay in patients with infections caused by bacteria-producing extended-spectrum beta-lactamases: a systematic review and meta-analysis.

OBJECTIVE: To assess the variation of effect estimates in the analysis of mortality and length of stay (LOS) in patients with infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. DESIGN: Systematic review and meta-analysis METHODS: Literature search for clinical studies from 1 January 1960 to 1 October 2018 was conducted in PubMed. Primary outcomes were risk ratios (RRs) of all-cause and attributable mortality and weighted mean differences (WMDs) in LOS in patients with bloodstream infections (BSIs) and non-invasive infections. Any change in the effect estimates was assessed by grouping studies according to design, setting, economy-based country classification, reporting period, microbiological aetiology, infection type and adjustment for appropriateness of empirical treatment. The impact of ESBL production was calculated using random-effect meta-analysis and heterogeneity was evaluated by I2 statistics and metaregression. RESULTS: Eighty-four studies including 22 030 patients and 149 outcome measures were included in the meta-analysis. Most studies were retrospective cohorts from high-income countries, providing unadjusted estimates. ESBL production in patients with BSIs (56 studies) increased the RR for all-cause mortality by a factor of 1.70 (95% CI 1.52 to 1.90; p<0.001), attributable mortality (16 studies) by 1.75 (95% CI 1.448 to 2.108; p<0.001) and WMD in the intensive care unit by 3.07 days (95% CI 1.61 to 4.54; p<0.001). WMD in hospital LOS was significantly higher in BSIs (4.41 days; 95% CI 3.37 to 5.46; p<0.001) and non-invasive (2.19 days; 95% CI 1.56 to 2.81; p<0.001). Subgroup analyses showed variation of estimates by study design, population, strain and assessment of appropriateness of empiric treatment. High heterogeneity was observed in all analyses. CONCLUSIONS: Current evidence of the clinical burden of infections caused by ESBL-producing bacteria is highly heterogeneous and based mainly on unadjusted estimates derived from retrospective studies. Despite these limitations, ESBL production in strains causing BSIs seems associated with higher all-cause and attributable mortality and longer hospitalisation.

Effects of an antimicrobial stewardship intervention on perioperative antibiotic prophylaxis in pediatrics.

Purpose: This study aims to determine the effectiveness of an Antimicrobial Stewardship Program based on a Clinical Pathway (CP) to improve appropriateness in perioperative antibiotic prophylaxis (PAP). Materials and methods: This pre-post quasi-experimental study was conducted in a 12 month period (six months before and six months after CP implementation), in a tertiary Pediatric Surgical Centre. All patients from 1 month to 15 years of age receiving one or more surgical procedures were eligible for inclusion. PAP was defined appropriate according to clinical practice guidelines. Results: Seven hundred sixty-six children were included in the study, 394 in pre-intervention and 372 in post-intervention. After CP implementation, there was an increase in appropriate PAP administration, as well as in the selection of the appropriate antibiotic for prophylaxis, both for monotherapy (p = 0.02) and combination therapy (p = 0.004). Even the duration of prophylaxis decreased during the post-intervention period, with an increase of correct PAP discontinuation from 45.1 to 66.7% (p < 0.001). Despite the greater use of narrow-spectrum antibiotic for fewer days, there was no increase in treatment failures (10/394 (2.5%) pre vs 7/372 (1.9%) post, p = 0.54). Conclusions: CPs can be a useful tool to improve the choice of antibiotic and the duration of PAP in pediatric patients.

Treatment of Community-Acquired Pneumonia: Are All Countries Treating Children in the Same Way? A Literature Review.

Background: Pneumonia represents an important threat to children's health in both developed and developing countries. In the last 10 years, many national and international guidelines on the treatment of pediatric CAP have been published, in order to optimize the prescription of antibiotics and limit their cost and side effects. However, the practical implementation of these guidelines is still limited. Main Text: We analyzed the current recommendations for the therapy of pediatric community-acquired pneumonia (CAP) that all converge on the identification of aminopenicillins and beta-lactams as the optimal treatment for CAP. We also conducted a review of the current literature on antibiotic regimens used for pediatric CAP to identify the current state of guidelines implementation in different settings. We selected 37 studies published from 2010 to 2016, including both retrospective and prospective studies, mainly cross-sectional and hospital based. The results show a global heterogeneity in the antibiotics prescription for pediatric CAP, with application of guidelines varying from 0% to more than 91% and with important differences even within the same country. Conclusions: Our review has demonstrated that the implementation of the guidelines is still limited but also that achieving the optimal prescription is possible and can be done in both developed and developing countries.

Disseminated Mycobacterium chimaera infection after open heart surgery in an Italian woman: a case report and a review of the literature.

We report the first Italian case of Mycobacterium chimaera disseminated infection in a patient with a history of cardiac surgery. The patient was initially diagnosed with sarcoidosis and started on immunosuppressive therapy. Ten months later she developed a vertebral osteomyelitis: M. chimaera was isolated from bone specimen. A review of the literature shows that M. chimaera infection occurs specifically in this population of patients, due to contamination of heater-cooler units used during cardiosurgery. Devices responsible for the transmission were produced by Sorin Group Deutschland. Mycobacterium chimaera infection should be included in the differential diagnosis for patients undergoing cardiac surgery.

Comparing imported malaria in adults and children presenting to an Italian teaching hospital: A 10-year retrospective study.

BACKGROUND: Malaria is not endemic in Italy, but it still represents an important threat to the travelers' health. With this study we wanted to compare the characteristics of imported malaria between adults and children. METHOD: This retrospective observational study includes all patients admitted to the Infectious Diseases Unit and in the Pediatric Department of Padua (Italy), and discharged with a diagnosis of malaria from 2005 to 2015. The variables considered are epidemiological and clinical. RESULTS: 172 cases of imported malaria were studied (124 adults and 48 children), P. falciparum was responsible for 90,7% of the cases, and was contracted mostly in Africa (96,5%), especially by foreigners visiting friends and relatives (VFR). Chemoprophylaxis was adopted only by few patients. 93% of all the patients developed the uncomplicated malaria, but pediatric patients had severe malaria significantly more often than adults (OR = 4,06, p = 0,015). Children also had significantly lower hemoglobin levels and higher parasitemia. The drugs used to treat the two groups were substantially different, but both had a good overall outcome. CONCLUSIONS: In order to reduce the risk of imported malaria, educational actions should target potential VFR travelers, and they should underline the different risk of severe malaria in adults and children. A further implementation of the recommended therapies could improve the patients' outcome.