A case of fatal monkeypox infection: necropsy and molecular findings, with some considerations related to clinical management.

OBJECTIVE: Human monkeypox (mpox) is usually self-limited infection; however, rising data show a worse outcome in patients with impaired immune status, particularly those co-infected with HIV [Mitjà O, Alemany A, Marks M, Lezama Mora JI, Rodríguez-Aldama JC, Torres Silva MS et al. Mpox in people with advanced HIV infection: A global case series. Lancet. 2023; 401:939-49. DOI:https://doi.org/10.1016/S0140-6736(23)00273-8] [Govind A, Lazarte SM, Kitchell E, Chow JY, Estelle CD, Fixsen E et al. Severe mpox infections in people with uncontrolled human immunodeficiency virus (HIV). Clin Infect Dis. 2023; 76:1843-6. DOI:https://doi.org/10.1093/cid/ciad052]. METHODS: We report the clinical, pathological, and molecular study of a patient with mpox infection and a late HIV diagnosis, with fatal outcome. RESULTS: Necropsy revealed visceral spread of mpox. Mpox virus was sequenced twice during the admission, uncovering an emerging mutation near a genomic region where mutations associated with tecovirimat resistance have been documented. DISCUSSION: Monkeypox can manifest as an opportunistic infection in individuals with advanced HIV-associated immunosuppression.

Stability Studies of Antipseudomonal Beta Lactam Agents for Outpatient Therapy.

Outpatient parenteral antimicrobial therapy (OPAT) is a useful treatment strategy against Pseudomonas aeruginosa and other multidrug-resistant bacteria. However, it is hindered by the lack of stability data for the administration of antibiotics under OPAT conditions. Our objective was to investigate the stability of nine antipseudomonal and broad-spectrum beta lactam antibiotics (aztreonam, cefepime, cefiderocol, ceftazidime, ceftazidime/avibactam, ceftolozane/tazobactam, meropenem, meropenem/vaborbactam, and piperacillin/tazobactam) to allow the spread of OPAT programs. All the antibiotics were diluted in 500 mL 0.9% sodium chloride and stored at 4, 25, 32, and 37 °C for 72 h in two different devices (infusion bags and elastomeric pumps). The solutions were considered stable if the color, clearness, and pH remained unchanged and if the percentage of intact drug was ≥90%. All the antimicrobials remained stable 72 h under refrigerated conditions and at least 30 h at 25 °C. At 32 °C, all the antibiotics except for meropenem and meropenem/vaborbactam remained stable for 24 h or more. At 37 °C, only aztreonam, piperacillin/tazobactam, cefepime, cefiderocol, and ceftolozane/tazobactam were stable for at least 24 h. The stability results were the same in the two devices tested. All the antibiotics studied are actual alternatives for the treatment of antipseudomonal or multidrug-resistant infections in OPAT programs, although the temperature of the devices is crucial to ensure antibiotic stability.

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort.

OBJECTIVES: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). METHODS: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. RESULTS: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. CONCLUSION: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective.

Stability of temocillin in outpatient parenteral antimicrobial therapy: is it a real option?

BACKGROUND: Temocillin is an interesting alternative to carbapenems for susceptible Enterobacteriaceae. Although its use in outpatient parenteral antimicrobial therapy (OPAT) programmes has generated interest, this has been hampered by the lack of stability data. OBJECTIVES: The purpose of the present study was to evaluate the physical and chemical stability of temocillin at the recommended dose for its use in OPAT programmes, contained in polypropylene infusion bags or polyisoprene elastomeric devices at different temperatures, and to describe a novel LC-MS/MS developed for the quantification of temocillin. METHODS: Temocillin daily dose (6 g) was diluted in 500 mL of 0.9% sodium chloride to obtain a final concentration of 12 g/L. This solution was stored at 4°C, 25°C, 32°C and 37°C for 72 h, both in polypropylene infusion bags and in polyisoprene elastomeric pumps. Physical and chemical stability were evaluated during 72 h after manufacturing. Solutions were considered stable if colour, clearness and pH remained unchanged and if the percentage of intact drug was ≥90%. RESULTS: Temocillin attained the chemical stability criterion of ≥90% of the original concentration for the whole experiment in both devices at 4°C, 25°C and 32°C. At 37°C, temocillin was stable for 24 h but its concentration dropped below 90% from that timepoint. No precipitation occurred and minor colour changes were observed. CONCLUSIONS: Temocillin is stable under OPAT conditions and it would be an appropriate candidate for the treatment of patients who can be discharged to complete therapy in an OPAT programme. For this study, an LC-MS/MS method was developed.

Treatment of Enterococcus faecalis Infective Endocarditis: A Continuing Challenge.

Today, Enterococcus faecalis is one of the main causes of infective endocarditis in the world, generally affecting an elderly and fragile population, with a high mortality rate. Enterococci are partially resistant to many commonly used antimicrobial agents such as penicillin and ampicillin, as well as high-level resistance to most cephalosporins and sometimes carbapenems, because of low-affinity penicillin-binding proteins, that lead to an unacceptable number of therapeutic failures with monotherapy. For many years, the synergistic combination of penicillins and aminoglycosides has been the cornerstone of treatment, but the emergence of strains with high resistance to aminoglycosides led to the search for new alternatives, like dual beta-lactam therapy. The development of multi-drug resistant strains of Enterococcus faecium is a matter of considerable concern due to its probable spread to E. faecalis and have necessitated the search of new guidelines with the combination of daptomycin, fosfomycin or tigecycline. Some of them have scarce clinical experience and others are still under investigation and will be analyzed in this review. In addition, the need for prolonged treatment (6-8 weeks) to avoid relapses has forced to the consideration of other viable options as outpatient parenteral strategies, long-acting administrations with the new lipoglycopeptides (dalbavancin or oritavancin), and sequential oral treatments, which will also be discussed.

Stability of Ampicillin plus Ceftriaxone Combined in Elastomeric Infusion Devices for Outpatient Parenteral Antimicrobial Therapy.

Currently, ampicillin plus ceftriaxone (AC) is one of the preferred treatments for Enterococcus faecalis infective endocarditis. However, there is a lack of stability data for the combination of both drugs in elastomeric devices, so the inclusion of AC in Outpatient Parenteral Antimicrobial Therapy (OPAT) programs is challenging. The objective of the study was to determine the stability of AC in elastomeric pumps when stored at 8 ± 2 °C, 25 ± 2 °C, 30 ± 2 °C and 37 ± 2 °C using LC-MS/MS. The combination was diluted in 0.9% sodium chloride and the final concentrations were ampicillin 24 g/L plus ceftriaxone 8 g/L. Physical and chemical stability were evaluated at 12, 20, 24, 36 and 48 h after preparation. Stability was met at each time point if the percentage of intact drug was ≥90% of its respective baseline concentration and color and clearness remained unchanged. The drug combination was stable for 48 h when it was kept at 8 ± 2 °C. At 25 ± 2 °C and 30 ± 2 °C, they were stable for 24 h of storage. At 37 ± 2 °C, the stability criterion was not met at any time point. These results prove that AC could be included in OPAT programs using elastomeric infusion devices for the treatment of E. faecalis infections.

[Epidemiology of leptospirosis in the wetlands of Southern Spain]. / Epidemiología de la leptospirosis en los humedales del sur de España.

OBJECTIVE: To find out whether the leptospirosis incidence rate among red swamp crayfish collectors in the harvesting season is higher than in the general population, and to identify risk factors and assess the direct and indirect health costs associated with leptospirosis seroconversion. METHOD: This study was carried out between 1 July 2017 and 31 March 2018 in the municipality of Isla Mayor (Seville, Spain). It took the form of a prospective cohort study (exposed population: swamp crayfish collectors; non-exposed population: general population). The population was invited to take part in a prevalence study to be conducted using the ELISA qualitative technique, and informed consent was obtained from those who agreed. Negative serology cases were then included in the cohort study. Both cohorts were monitored clinically and symptomatic cases were serology tested. A second serum sample was taken from the swamp crayfish collectors at the end of the monitoring period to detect asymptomatic cases. Serovars were confirmed by microscopic agglutination testing. A bivariate descriptive analysis was carried out and cumulative incidence and relative risk were calculated, with positive serology being taken as the dependent variable. RESULTS: A total of 278 people were included in the study, of whom 92 made up the swamp crayfish collectors cohort and 186 the general population cohort. Women made up 46.8% of the sample, but only 29.3% of the collectors cohort. The mean age was 45.1 (±16.4) years. Nine cases of seroconversion were detected: eight among swamp crayfish collectors and one in the general population. Overall cumulative incidence was therefore 3.2%: 8.7% in the exposed group and 0.5% in the non-exposed group. Relative risk was 16.2% (95% confidence interval: 2.1-127.4). The total cost of medical assistance and illness-related losses associated with leptospirosis was 1568€/case. CONCLUSIONS: Leptospirosis in Isla Mayor is strongly associated with red swamp crayfish collecting. It's incidence here is much higher than that reported in studies published in other countries.

Epidemiología de la leptospirosis en los humedales del sur de España / Epidemiology of leptospirosis in the wetlands of Southern Spain

Objetivo: Conocer si la incidencia de leptospirosis en los capturadores de cangrejo rojo durante el periodo de captura es superior a la de la población general, así como identificar factores de riesgo y estimar los costes sanitarios directos e indirectos asociados a los casos de seroconversión de dicha enfermedad.Método: Este estudio se realizó desde el 1 de julio de 2017 hasta el 31 de marzo de 2018. Se llevó a cabo un estudio de cohortes prospectivo (población expuesta: capturadores de cangrejo rojo; población no expuesta: población general) en el municipio de Isla Mayor (Sevilla, España). Previo consentimiento informado, se invitó a la población al estudio de prevalencia mediante la técnica cualitativa ELISA. Los que tuvieron serología negativa fueron incluidos en el estudio de cohortes. Ambas cohortes se siguieron clínicamente y a los casos sintomáticos se les realizó serología. A los capturadores de cangrejo rojo se les tomó una segunda muestra de suero al final del seguimiento para detectar asintomáticos. La serovariedad se confirmó mediante aglutinación microscópica. Se realizó un análisis descriptivo bivariado y se calcularon la incidencia acumulada y el riesgo relativo. La serología positiva se tomó como variable dependiente.Resultados:Se incluyeron en el estudio 278 personas, de las que 92 constituían la cohorte de capturadores y 186 la de población general. El 46,8% de la muestra eran mujeres, aunque entre los capturadores de cangrejo rojo estas solo representaban el 29,3%. La edad media de la muestra fue de 45,1 (± 16,4) años. Se detectaron nueve seroconversiones: ocho en capturadores de cangrejo rojo y una en población general. Por lo tanto, la incidencia acumulada fue de 8,7% en capturadores de cangrejo rojo y de 0,5% en población general, siendo el riesgo relativo de 16,2 (intervalo de confianza del 95%: 2,1-127,4). El coste total de la asistencia sanitaria y de las pérdidas por enfermedad asociadas a la leptospirosis fue de 1568 € por caso(AU)

Objective: To find out whether the leptospirosis incidence rate among red swamp crayfish collectors in the harvesting season is higher than in the general population, and to identify risk factors and assess the direct and indirect health costs associated with leptospirosis seroconversion. Method: This study was carried out between 1 July 2017 and 31 March 2018 in the municipality of Isla Mayor (Seville, Spain). It took the form of a prospective cohort study (exposed population: swamp crayfish collectors; non-exposed population: general population). The population was invited to take part in a prevalence study to be conducted using the ELISA qualitative technique, and informed consent was obtained from those who agreed. Negative serology cases were then included in the cohort study. Both cohorts were monitored clinically and symptomatic cases were serology tested. A second serum sample was taken from the swamp crayfish collectors at the end of the monitoring period to detect asymptomatic cases. Serovars were confirmed by microscopic agglutination testing. A bivariate descriptive analysis was carried out and cumulative incidence and relative risk were calculated, with positive serology being taken as the dependent variable. Results: A total of 278 people were included in the study, of whom 92 made up the swamp crayfish collectors cohort and 186 the general population cohort. Women made up 46.8% of the sample, but only 29.3% of the collectors cohort. The mean age was 45.1 (±16.4) years. Nine cases of seroconversion were detected: eight among swamp crayfish collectors and one in the general population. Overall cumulative incidence was therefore 3.2%: 8.7% in the exposed group and 0.5% in the non-exposed group. Relative risk was 16.2% (95% confidence interval: 2.1-127.4). The total cost of medical assistance and illness-related losses associated with leptospirosis was 1568€/case. (AU)

Clinical Outcomes of an Innovative Cefazolin Delivery Program for MSSA Infections in OPAT.

Cefazolin is a recommended treatment for methicillin-susceptible Staphylococcus aureus (MSSA) infections that has been successfully used in outpatient parenteral antibiotic therapy (OPAT) programs. The aim of this study was to assess the clinical outcomes of cefazolin delivered each day (Group 24) vs. every two days (Group 48) for MSSA infections in OPAT programs. It was a prospective observational study with retrospective analysis of a cohort of MSSA infections attended in OPAT. The primary outcome was treatment success, defined as completing the antimicrobial regimen without death, treatment discontinuation, or readmission during treatment and follow-up. A univariate and multivariate logistic regression model was built. A two-sided p < 0.05 was considered statistically significant. Of the 149 MSSA infections treated with cefazolin 2 g/8 h in OPATs, 94 and 55 patients were included in the delivery Group 24 and Group 48, respectively. Treatment failure and unplanned readmission rates were similar in both groups (11.7% vs. 7.3% p = 0.752 and 8.5% vs. 5.5% p = 0.491). There was a significant increase in vascular access complications in Group 24 (33.0%) with respect to Group 48 (7.3%) (p < 0.001). Treating uncomplicated MSSA infection with cefazolin home-delivered every two days through an OPAT program is not associated with an increased risk of treatment failure and entails a significant reduction in resource consumption compared to daily delivery.

Probable ertapenem-induced encephalopathy; case report and suggested alternatives for chronic prostatitis.

Ertapenem is a carbapenem antibiotic usually reserved for complicated infections. Drug-induced neurotoxicity is a rare adverse reaction associated with ertapenem, and may be directly related to its chemical structure. We report a case of a 64-year-old male with a hematological history and chronic prostatitis that was admitted to hospital for gait instability, clumsiness, dysarthria and tremors. He started ertapenem intravenous 1 g once daily a week prior to admission. Creatinine clearance calculation by the Cockcroft-Gault method was 52 mL/min and total protein levels were low. Ertapenem's administration was discontinued and the patient's neurological symptoms improved dramatically just one day after. The result of the Naranjo Scale was six, suggesting a probable adverse drug reaction. We discussed if he could receive meropenem in case of severe infection such as septic shock. Considering the patient's medical history, the chemical structure of meropenem and the fact that there are almost no reported cases of neurotoxicity from this drug, we assume that meropenem could be used in case of severe infection in patients with history of neurotoxicity caused by ertapenem if no added risk factors are present, such as renal failure.

Blood culture-negative infective endocarditis: a worse outcome? Results from a large multicentre retrospective Spanish cohort study.

BACKGROUND: To assess the impact of blood cultures negative infective endocarditis (BCNIE) on in-hospital mortality. METHODS: Prospective multicentre study with retrospective analysis of a Spanish cohort including adult patients with definite IE. Cardiac implantable devices infection were excluded. Comparisons between blood cultures positive and BCNIE groups were performed to analyse in-hospital mortality. RESULTS: 1001 cases were included of which 83 (8.3%) had BCNIE. Alternative microbiological diagnosis was achieved for 39 (47%) out 83 cases. The most frequent identifications were: Coxiella burnetii (11; 28.2%), Tropheryma whipplei (4; 10.3%), Streptococcus gallolyticus (4;10.3%) and Staphylococcus epidermidis (3; 7.7%). Surgery was performed more frequently in BCNIE group (57.8 vs. 36.9%, p < .001). All-cause in-hospital mortality rate was 26.7% without statistical difference between compared groups. BCNIE was not associated to worse mortality rate in Cox regression model (aHR = 1.37, 95% CI 0.90-2.07, p = .14). Absence of microbiological diagnosis was also not associated to worse in-hospital prognosis (aHR = 1.62, 95% CI 0.99-2.64, p = .06). CONCLUSIONS: In our cohort, BCNIE was not associated to greater in-hospital mortality based in multivariate Cox regression models. The variables most frequently associated with mortality were indicated but not performed surgery (aHR = 2.48, 95% CI 1.73-3.56, p < .001), septic shock (aHR = 2.24, 95% CI 1.68-2.99, p < .001), age over 65 years (aHR = 1.88, 95% CI 1.40-2.52, p < .001) and complicated endocarditis (aHR = 1.79, 95% CI 1.36-2.37, p < .001).

Stability of Antimicrobials in Elastomeric Pumps: A Systematic Review.

Outpatient parenteral antimicrobial therapy (OPAThttp) programs have become an important healthcare tool around the world. Portable elastomeric infusion pumps are functional devices for ambulatory delivery of antimicrobial drugs, and their stability is an essential point to guarantee an appropriate infusion administration. We conducted a systematic review to provide a synthesis and a critical evaluation of the current evidence regarding antimicrobial stability in elastomeric pumps. Data sources were PubMed, EMBASE, and Web of Sciences. The review protocol was registered on the Center for Open Science, and it was carried out following the PRISMA guidelines. Studies were eligible if the aim was the evaluation of the physicochemical stability of an antimicrobial agent stored in an elastomeric device. Of the 613 papers identified, 33 met the inclusion criteria. The most studied group of antimicrobials was penicillins, followed by cephalosporins and carbapenems. In general, the stability results of the antimicrobials that have been studied in more than one article agree with each other, with the exception of ampicillin, flucloxacillin, and ceftazidime. The antibiotics that displayed a longer stability were glycopeptides and clindamycin. Regarding the stability of antifungals and antivirals, only caspofungin, voriconazole, and ganciclovir have been investigated. The information provided in this article should be considered in patient treatments within the OPAT setting. Further stability studies are needed to confirm the appropriate use of the antimicrobials included in this program to ensure optimal patient outcomes.

Ampicillin Plus Ceftriaxone Combined Therapy for Enterococcus faecalis Infective Endocarditis in OPAT.

Ampicillin plus ceftriaxone (AC) is a well-recognized inpatient regimen for Enterococcus faecalis infective endocarditis (IE). In this regimen, ceftriaxone is usually administered 2 g every 2 h (AC12). The administration of AC in outpatient parenteral antibiotic treatment (OPAT) programs is challenging because multiple daily doses are required. AC regimens useful for OPAT programs include once-daily high-dose administration of ceftriaxone (AC24) or AC co-diluted and jointly administered in bolus every 4 h (ACjoined). In this retrospective analysis of prospectively collected cases, we aimed to assess the clinical effectivity and safety of three AC regimens for the treatment of E. faecalis IE. Fifty-nine patients were treated with AC combinations (AC12 n = 32, AC24 n = 17, and ACjoined n = 10). Six relapses occurred in the whole cohort: five (29.4%) treated with AC24 regimen and one (10.0%) with ACjoined. Patients were cured in 30 (93.3%), 16 (94.1%), and eight (80.0%) cases in the AC12, AC24 and ACjoined groups, respectively. Unplanned readmission occurred in eight (25.0%), six (35.3%), and two (20.0%) patients in the AC12, AC24 and ACjoined groups, respectively. The outcome of patients with E. faecalis IE treated with AC in OPAT programs relies on an optimization of the delivery of the combination. AC24 exhibit an unexpected rate of failures, however, ACjoined might be an effective alternative which clinical results should corroborate in further studies.

Antifungal treatment administered in OPAT programs is a safe and effective option in selected patients / Tratamiento antifúngico endovenoso domiciliario: una alternativa segura y eficaz

INTRODUCTION: Outpatient parenteral antimicrobial therapy (OPAT) has been recognised as a useful, cost-effective and safe alternative to inpatient treatment. Nevertheless, the most common antimicrobials used are antibiotics, and there is less information about the use of antifungal therapy (AT). The aim of this study is to analyse a cohort of patients treated with AT administered via OPAT and to compare them with patients from the rest of the cohort (RC) treated with antibiotics. METHODS: Prospective observational study with post hoc (or retrospective) analysis of a cohort of patients treated in the OPAT program. We selected the patients treated with antifungals between July 2012 and December 2018. We recorded demographic and clinical data to analyse the validity of the treatment and to compare the differences between the AT and the RC. RESULTS: Of the 1101 patients included in the OPAT program, 24 (2.18%) were treated with AT, 12 Liposomal Amphotericin B, 6 echinocandins and 6 fluconazole. This result is similar to other cohorts. There were differences between the AT vs RC in the number of patients with neoplasia (58.3% vs 28%; p = 0.001), IC Charlson > 2 (58.3% vs 38.8; p = 0.053), duration of treatment (15 days vs 10.39 days; p = 0.001) and patients with central catheters (54.2% vs 21.7%; p = 0.0001). These differences are justified because there were more hematologic patients included in the AT group. Nevertheless, there were no differences in adverse reactions (25% vs 32.3%; p = 0.45) or re-admissions (12.5% vs 10%; p = 0.686) and OPAT with AT was successful in 21/24 patients (87.5%). CONCLUSIONS: AT can be successfully administered in OPAT programs in selected patients, that are clinically stable and monitored by an infectious disease physician

INTRODUCCIÓN: El tratamiento antimicrobiano domiciliario endovenoso (TADE) ha sido reconocido como una alternativa al tratamiento hospitalario útil, eficiente y seguro. Sin embargo, los antimicrobianos más utilizados son los antibióticos, y existe menos información sobre el uso de la terapia antimicótica (TA). El objetivo de este estudio es analizar una cohorte de pacientes tratados con TA administrada mediante TADE y compararlos con pacientes del resto de la cohorte (RC) tratados con otros antibióticos. MÉTODOS: Estudio prospectivo observacional con análisis post hoc (o retrospectivo) de una cohorte de pacientes atendidos en el programa TADE. Seleccionamos a los pacientes tratados con antifúngicos entre julio de 2012 y diciembre de 2018. Registramos los datos demográficos y clínicos para analizar la validez del tratamiento y comparar las diferencias entre la TA y el RC. RESULTADOS: De los 1.101 pacientes incluidos en el programa TADE, 24 (2,18%) fueron tratados con TA: 12 anfotericina B liposómica, 6 equinocandinas y 6 fluconazol. Este resultado es similar a otras cohortes. Hubo diferencias entre la TA vs. RC en el número de pacientes con neoplasia (58,3 vs. 28%; p = 0,001), índice de Charlson > 2 (58,3 vs. 38,8; p = 0,053), duración del tratamiento (15 vs. 10,39 días; p = 0,001) y pacientes con catéteres centrales (54,2 vs. 21,7%; p = 0,0001). Estas diferencias están justificadas porque en el grupo TA se incluyeron más pacientes hematológicos. Sin embargo, no hubo diferencias en las reacciones adversas (25 vs. 32,3%; p = 0,45) o reingresos (12,5 vs. 10%; p = 0,686) y el TADE con TA tuvo éxito en 21/24 pacientes (87,5%). CONCLUSIONES: En pacientes seleccionados, clínicamente estables y en seguimiento por un médico de enfermedades infecciosas, la TA podría administrarse en programas TADE