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.

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).

Antifungal treatment administered in OPAT programs is a safe and effective option in selected patients.

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.

[Portal vein thrombosis associated with biliary tract infection]. / Trombosis portal asociada a infección de vía biliar.

OBJECTIVE: To describe the etiology, symptoms and management of portal vein thrombosis associated with biliary tract infection and to compare our findings with classical causes of pylephlebitis. MATERIAL AND METHODS: We performed a retrospective descriptive study of 10 patients in a tertiary hospital. RESULTS: Portal vein thrombosis was associated with biliary tract infection in seven patients and with classical causes of pylephlebitis in three. In both groups, symptoms consisted of fever and abdominal pain accompanied by leukocytosis and increased liver enzymes. Blood cultures were positive in most patients and the main complication was liver abscess. The therapeutic management and outcomes were similar in both groups. CONCLUSIONS: Portal vein thrombosis can be associated with biliary tract infection. Clinical presentation and outcomes are highly similar to those in classical causes of pylephlebitis.