Do specific antimicrobial stewardship interventions have an impact on carbapenem resistance in Gram-negative bacilli? A multicentre quasi-experimental ecological study: time-trend analysis and characterization of carbapenemases.

BACKGROUND: Carbapenem-resistant Gram-negative bacilli (CR-GNB) are among the most threatening microorganisms worldwide and carbapenem use facilitates their spread. Antimicrobial stewardship programmes (ASPs) can help to optimize the use of antibiotics. This study evaluates the impact of a multifaceted educational ASP on carbapenem use and on the epidemiology of CR-GNB. METHODS: We conducted a quasi-experimental, time-series study in seven hospitals, from January 2014 to September 2018. The key intervention was composed of educational interviews promoting the appropriate use of carbapenems. The primary endpoints were carbapenem consumption and incidence density (ID) of CR-GNB. All non-duplicated CR-GNB clinical isolates were tested using phenotypic assays and PCR for the presence of carbapenemases. Joinpoint regression and interrupted time-series analyses were used to determine trends. RESULTS: A decrease in carbapenem consumption throughout the study period [average quarterly percentage change (AQPC) -1.5%, P < 0.001] and a -8.170 (-16.064 to -0.277) level change following the intervention were observed. The ID of CR-Acinetobacter baumannii decreased (AQPC -3.5%, P = 0.02) and the overall ID of CR-GNB remained stable (AQPC -0.4%, P = 0.52). CR-GNB, CR-Pseudomonas aeruginosa and CR-A. baumannii IDs per hospital correlated with the local consumption of carbapenems. The most prevalent carbapenem resistance mechanisms were OXA-23 for CR-A. baumannii (76.1%), OXA-48 for CR-Klebsiella pneumoniae (66%) and no carbapenemases for CR-P. aeruginosa (91.7%). The epidemiology of carbapenemases was heterogeneous throughout the study, especially for carbapenemase-producing Enterobacteriaceae. CONCLUSIONS: In conclusion, a multifaceted, educational interview-based ASP targeting carbapenem prescribing reduced carbapenem use and the ID of CR-A. baumannii.

The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers.

BACKGROUNDPersistent controllers (PCs) maintain antiretroviral-free HIV-1 control indefinitely over time, while transient controllers (TCs) eventually lose virological control. It is essential to characterize the quality of the HIV reservoir in terms of these phenotypes in order to identify the factors that lead to HIV progression and to open new avenues toward an HIV cure.METHODSThe characterization of HIV-1 reservoir from peripheral blood mononuclear cells was performed using next-generation sequencing techniques, such as full-length individual and matched integration site proviral sequencing (FLIP-Seq; MIP-Seq).RESULTSPCs and TCs, before losing virological control, presented significantly lower total, intact, and defective proviruses compared with those of participants on antiretroviral therapy (ART). No differences were found in total and defective proviruses between PCs and TCs. However, intact provirus levels were lower in PCs compared with TCs; indeed the intact/defective HIV-DNA ratio was significantly higher in TCs. Clonally expanded intact proviruses were found only in PCs and located in centromeric satellite DNA or zinc-finger genes, both associated with heterochromatin features. In contrast, sampled intact proviruses were located in permissive genic euchromatic positions in TCs.CONCLUSIONSThese results suggest the need for, and can give guidance to, the design of future research to identify a distinct proviral landscape that may be associated with the persistent control of HIV-1 without ART.FUNDINGInstituto de Salud Carlos III (FI17/00186, FI19/00083, MV20/00057, PI18/01532, PI19/01127 and PI22/01796), Gilead Fellowships (GLD22/00147). NIH grants AI155171, AI116228, AI078799, HL134539, DA047034, MH134823, amfAR ARCHE and the Bill and Melinda Gates Foundation.

Dalbavancin as suppressive antibiotic therapy in patients with prosthetic infections: efficacy and safety.

Suppressive antibiotic therapy (SAT) is a strategy to alleviate symptoms and/or to reduce the progression of an infection when other treatment options cannot be used. Dalbavancin, due to its prolonged half-life, enables (bi) weekly dosing. Here, we report our multicenter real-life clinical experience with dalbavancin used as SAT in patients with prosthetic joint or vascular infections. Medical records of all adult patients with documented vascular or orthopedic chronic prosthetic infections, who received dalbavancin as SAT between 2016 and 2018 from four Spanish hospitals were reviewed for inclusion. Descriptive analysis of demographic characteristics, Charlson Comorbidity index, Barthel index, isolated pathogens and indication, concomitant antibiotic use, adverse events, and clinical outcome of SAT were performed. Eight patients were eligible for inclusion, where six patients had prosthetic vascular infections (aortic valve) and two patients had knee prosthetic joint infections. The most common pathogens were methicillin-susceptible Staphylococcus aureus and Enterococcus faecium. All patients had a history of prior antibiotic treatment for the prosthetic infection [median duration of antibiotic days 125 days (IQR, 28-203 days)]. The median number of dalbavancin doses was 29 (IQR, 9-61) and concomitant antibiotic use (n = 5, 62.5%). Clinical success was reported in 75% (n = 6) of patients. Adverse events were reported in two patients (mild renal and hepatic impairment). The median estimated cost savings due to the avoided hospital days was €60185 (IQR, 19,916-94984) per patient. Despite the limitations of our study, this preliminary data provides valuable insight to support further evaluation of dalbavancin for SAT in patients with prosthetic infections in the outpatient setting when alternative treatments are not feasible.

Mpox Infection and Sexually Transmitted Infections: A Cross-Sectional Study from a Secondary Hospital in the May-September 2022 International Outbreak.

The aims of this study were to describe the characteristics of patients infected by mpox in our setting, to determine the prevalence of mpox in samples that are classically used for diagnosing sexually transmitted infections (STIs) such as anal, urethral, pharyngeal, and urine, and to assess the prevalence of coinfection with STIs in the same samples. A cross-sectional study was conducted, collecting all confirmed cases of mpox between June and July 2022 using polymerase chain reaction. Sociodemographic data, HIV and other STI status, and prevalence of mpox and STIs in urethral, anal, pharyngeal, or urine samples were collected. Data from 22 patients were extracted, all of whom were men who have sex with men (MSM) and 54.5% were previously HIV positive. The median age was 43 years. All the skin samples were positive for mpox, followed by anal samples (n = 10, 45.5%). Mpox was isolated in 2 or more samples simultaneously in 12 (54%) cases. Nine (41%) patients were positive for an STI and four of them had more than one STIs (18.2%). Human mpox has been epidemiologically significant among MSM. Mpox should be investigated not only in skin lesions but also in samples classically used for STIs. Mpox, such as other STIs, shares ways of transmission and coinfection may be underdiagnosed.

Expanding HIV clinical monitoring: the role of CD4, CD8, and CD4/CD8 ratio in predicting non-AIDS events.

BACKGROUND: While a low CD4/CD8 ratio during HIV treatment correlates with immunosenescence, its value in identifying patients at an increased risk for clinical events remains unclear. METHODS: We analyzed data from the CoRIS cohort to determine whether CD4 count, CD8 count, and CD4/CD8 ratio at year two of antiretroviral therapy (ART) could predict the risk of serious non-AIDS events (SNAEs) during the next five years. These included major adverse cardiovascular events, non-AIDS-defining malignancies, and non-accidental deaths. We used pooled logistic regression with inverse probability weighting to estimate the survival curves and cumulative risk of clinical events. FINDINGS: The study included 4625 participants, 83% male, of whom 200 (4.3%) experienced an SNAE during the follow-up period. A CD4/CD8 ratio <0.3 predicted an increased risk of SNAEs during the next five years (OR 1.63, 95% CI 1.03-2.58). The effect was stronger at a CD4/CD8 ratio cut-off of <0.2 (OR 3.09, 95% CI 1.57-6.07). Additionally, low CD4 count at cut-offs of <500 cells/µL predicted an increased risk of clinical events. Among participants with a CD4 count ≥500 cells/µL, a CD8 count ≥1500 cells/µL or a CD4/CD8 ratio <0.4 predicted increased SNAE risk. INTERPRETATION: Our results support the use of the CD4/CD8 ratio and CD8 count as predictors of clinical progression. Patients with CD4/CD8 ratio <0.3 or CD8 count ≥1500/µL, regardless of their CD4 count, may benefit from closer monitoring and targeted preventive interventions. FUNDING: This work was supported by CIBER (CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea-NextGenerationEU; by the Spanish AIDS Research Network (RIS) RD16/0025/0001 project as part of the Plan Nacional R + D + I, and cofinanced by Instituto de Salud Carlos III (ISCIII)- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER), ISCIII projects PI18/00154, PI21/00141, and ERDF, "A way to make Europe", ICI20/00058.

Dalbavancin is a novel antimicrobial against Gram-positive pathogens: clinical experience beyond labelled indications.

Very limited labelled indications have been approved for the newer antimicrobials. Data on the clinical uses, efficacy and safety of dalbavancin are scarce, thus here we sought to describe our clinical experience. 16-month observational prospective study was performed. 19 (86%) were used under off-label indications. 10 (46%) for osteoarticular infections, 5 (23%) bloodstream infections and 3 (14%) endocarditis. To highlight, one patient received dalbavancin as long-term suppressive therapy. Most frequent use reasons were promptly hospital discharge, 11 (65%), and the presence of resistant organisms involving limited treatment options, 5 (23%). Successful outcome was observed in >95% of the patients and only 1 (4.5%) adverse event was reported. Further evidence beyond labelled indications is urgently needed. Despite the limitations, dalbavancin appears to be a safe and efficient option for adult patients who have tried and/or failed other therapies due to multidrug-resistant Gram-positive organisms.

Efficacy and safety of replacing lopinavir with atazanavir in HIV-infected patients with undetectable plasma viraemia: final results of the SLOAT trial.

BACKGROUND: Atazanavir seems to be a protease inhibitor (PI) with a more favourable metabolic profile. Information regarding the potential benefit of replacing lopinavir/ritonavir by atazanavir in HIV-infected patients with prolonged viral suppression is scarce. If proved, this strategy could be particularly attractive for the subset of patients with greater cardiovascular risk. METHODS: SLOAT was a prospective, open, comparative trial in which patients receiving lopinavir/ritonavir-based regimens and having undetectable plasma HIV-RNA for longer than 24 weeks were randomized to continue on the same therapy or switch to atazanavir. Outcomes in viral rebound, CD4 counts, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides and glucose were compared in both groups of patients at 48 weeks of follow-up. RESULTS: A total of 189 patients were recruited and took at least the first dose of the assigned treatment arm. Overall, 102 switched to atazanavir (49 on 400 mg once daily, and 53 on 300 mg plus 100 mg of ritonavir once daily due to concomitant tenofovir use) and 87 continued on lopinavir/ritonavir. All patients received the PI along with two nucleoside analogues. Virological failure occurred in 12 patients switched to atazanavir and 9 continuing on lopinavir/ritonavir. A reduction (P < 0.001) in median total cholesterol (-19 mg/dL) and triglycerides (-80 mg/dL) was observed after 48 weeks of atazanavir switching, whereas no significant changes occurred in the lopinavir/ritonavir arm. Greater reductions in total cholesterol and triglycerides were seen in patients switched to atazanavir without ritonavir boosting. CONCLUSIONS: The replacement of lopinavir/ritonavir by atazanavir provides an overall significant reduction in total cholesterol and triglycerides, without increased risk of virological failure.

Cómo comunicar malas noticias en la era COVID / How to communicate bad news in the COVID era

Comunicar en el ámbito de las ciencias de la Salud no es sencillo, la formación es escasa y poco reglada. La información a comunicar no suele ser buena y dependiendo de cómo se haga se puede contener mucho dolor o agravar el sufrimiento del que la recibe. En tiempos de pandemia, la cuestión de la comunicación se agrava debido a las restricciones en el acceso a los pacientes y familia, sumada las tensiones propias de momentos de máxima presión asistencial. Un enfoque práctico, humano, centrado en el receptor de la información es lo que pretendo transmitir. (AU)

Outbreak of syphilis, but not of acute hepatitis C, among HIV-infected homosexual men in Madrid.

BACKGROUND: Clustered cases of acute hepatitis C virus (HCV) infection, frequently accompanied by sexually transmitted diseases, have recently been reported among men who have sex with men (MSM) in several European cities. METHOD: We performed a retrospective record of cases of syphilis in a large cohort of HIV-infected individuals on regular follow-up in Madrid, Spain. HCV testing was carried out in all of them. RESULTS: A total of 53 diagnosis of syphilis were made during the previous 4 years (2002 to 2005) in 729 HIV-infected MSM on regular follow-up. However, in only 2 of them (3.7%) asymptomatic HCV seroconversion occurred at the time of the syphilis episode. Both patients developed chronic hepatitis C. CONCLUSION: Acute HCV infection should periodically be ruled out in all HIV-infected MSM engaged in sexual risky behaviors presenting with syphilis.

Sustained virological response following HCV therapy is associated with non-progression of liver fibrosis in HCV/HIV-coinfected patients.

BACKGROUND: Chronic hepatitis C leads to progressive liver fibrosis, which is accelerated in HIV-coinfected patients. Unfortunately, hepatitis C virus (HCV) therapy provides sustained virological response (SVR) to only 40% of coinfected patients. Little is known about the regression of hepatic fibrosis in treated patients. METHODS: All coinfected patients who had completed a full course of HCV therapy at our institution were identified. Liver fibrosis staging was estimated using non-invasive procedures at the time of initiating HCV therapy and reassessed at the last patient's follow-up using elastometry (FibroScan). RESULTS: A total of 103 coinfected patients were identified. HCV genotype distribution was 1 (63%), 3 (29%) and 4 (8%). SVR had been attained by 34 individuals, while the remaining 69 were non-responders and/or relapsers. The mean lag time between the end of HCV therapy and the current assessment of liver fibrosis was 40 months, without differences between groups. Metavir score estimates were comparable before initiating HCV therapy in SVR and non-SVR patients. By contrast, current Metavir scores were lower in SVR than in non-SVR patients; for instance, F3-F4 estimates were 12% versus 54%, respectively (P < 0.001). Moreover, the longer the time elapsed after HCV therapy, the lower the liver fibrosis in SVR patients (rho = -0.39; P = 0.02). Conversely, liver fibrosis staging directly correlated with the lag following HCV therapy in non-SVR patients (rho = 0.25; P = 0.03). CONCLUSIONS: SVR after HCV therapy is associated with non-progression of liver fibrosis in HCV/HIV-coinfected patients, although this benefit may not be universal and improvement only been recognizable after several years of follow-up.

Brote de bacteriemia por Pantoea agglomerans en hemodiálisis. Una infección por un invitado no esperado / Bacteremia outbreak due to Pantoea agglomerans in hemodialysis, an infection by an unexpected guest

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Acerca de un caso de coproporfiria hereditaria con afectación neurológica, hematológica y renal / A case report of hereditary coproporphyria with neurological, haematological and renal involvement

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Fracaso renal agudo posrenal secundario a seudomixoma peritoneal tras apendicectomía; una entidad infrecuente / Post-renal acute renal failure secondary to peritoneal Pseudomyxoma after appendectomy; an uncommon entity

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Telbivudine: a new option for the treatment of chronic hepatitis B.

Chronic hepatitis B virus (HBV) infection affects > 350 million individuals worldwide. Chronic hepatitis B is associated with complications of end-stage liver disease, including cirrhosis and hepatocellular carcinoma. HBV replication is the best predictor of liver disease progression to cancer, and antiviral therapy may diminish or halt this unfavorable outcome. Six drugs have been approved for the treatment of chronic hepatitis B: interferon-alpha(2b), pegylated interferon-alpha(2a), lamivudine, adefovir, entecavir and telbivudine. Most agents designed to target hepatitis B are hindered by the development of resistance, poor tolerability or limited efficacy; therefore, new agents and treatment strategies are needed. Telbivudine is the latest approved anti-HBV agent; it is an orally administered nucleoside analog that selectively inhibits HBV replication. It has demonstrated potent activity against HBV in Phase III clinical studies, with good tolerance, lack of mitochondrial toxicity and no dose-limiting side effects.

Treatment of chronic hepatitis B or C in HIV-infected patients with dual viral hepatitis.

Dual chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are recognized in 3%-5% of human immunodeficiency virus (HIV)-infected individuals. More severe liver disease is seen in these patients. Viral interference may account for the fact that replication of one virus generally predominates over replication of the other. The impact that treatment of HBV or HCV infection has on this reciprocal inhibition is not well established. No evidence of reactivation of either HBV or HCV was seen when complete suppression of the other predominant virus was achieved with specific therapy in 21 subjects with HIV infection and dual HBV/HCV infections. This information has important pathogenic implications and may influence therapeutic decisions.