Ertapenem in outpatient parenteral antimicrobial therapy for complicated urinary tract infections.

BACKGROUND: Ertapenem is a broad-spectrum antibiotic that is increasingly being utilized. Its dosing convenience renders it suitable for outpatient therapy, and its pharmacokinetic characteristics favour its use against complicated urinary tract infections (cUTIs). Despite this, sufficient clinical data are lacking for its use against cUTIs in the outpatient setting. We assessed the microbiological and clinical cure rates associated with ertapenem treatment for cUTIs in two outpatient parenteral antimicrobial therapy (OPAT) departments. METHODS: We undertook a prospective observational study of adult patients who received ertapenem for cUTIs between August 2010 and August 2014. Data on patient characteristics, clinical progress and microbiological results were collected and analysed. RESULTS: Sixty-one patients were enrolled. The median age was 59 years (range 24, 83) and 61% were male. The most common diagnoses were pyelonephritis (39%) and prostatitis (15%). The most common causative organism was Escherichia coli (67%). Extended-spectrum ß-lactamase (ESBL)-producing organisms were detected in 72% of infections. Microbiological cure was achieved in 67% overall, and was less likely in those with Klebsiella pneumoniae infection (OR = 0.21 [95%CI: 0.05 to 0.85] p = 0.029). Clinical cure was observed in 92% of patients. CONCLUSION: In this study of treating cUTIs with ertapenem, we have demonstrated good clinical outcomes. A lower than expected microbiological cure rate was observed in those with Klebsiella pneumoniae infection.

Pharmacokinetics of ertapenem in outpatients with complicated urinary tract infections.

OBJECTIVES: Ertapenem is a broad-spectrum carbapenem antibiotic used to treat severe bacterial infections. In view of its dosing convenience, it is increasingly used as outpatient therapy. The objective of this study was to determine the pharmacokinetics and renal disposition of ertapenem in outpatients with complicated urinary tract infections. METHODS: Ertapenem was administered as a daily intravenous infusion of 1 g over 30 min. At steady-state, blood and urine samples were collected over one dosing interval. Drug concentrations in serum and urine were determined using a validated liquid chromatography-tandem mass spectrometry method. A population pharmacokinetic model was used to characterize ertapenem serum and urine profiles. The likelihood of the standard dosing achieving a favourable pharmacokinetic-pharmacodynamic exposure was evaluated using Monte Carlo simulations. RESULTS: Ten adult male patients were studied. Concentration-time profiles of ertapenem in both serum (r(2) =0.997) and urine (r(2) =0.982) were captured satisfactorily. Mean values for volume of distribution, clearance and elimination t½ were 4.8 L, 0.7 L/h and 6.1 h, respectively. A high ertapenem concentration (>128 mg/L) could be attained in the urine at 40% of the dosing interval. CONCLUSIONS: The pharmacokinetics of ertapenem in serum and urine were characterized. Our simulations suggested that a sufficiently high ertapenem concentration could be achieved in urine to overcome low to intermediate resistance. Clinical investigations to validate our findings are warranted.

An outcomes analysis of outpatient parenteral antibiotic therapy (OPAT) in a large Asian cohort.

Outpatient parenteral antibiotic therapy (OPAT) facilitates early discharge, easing demands on inpatient resources and allowing patients the opportunity to restore home life. In Singapore, two large hospitals established a common prospective database in 2006. This study presents an analysis of all enrolled cases over 6 years to consider factors potentially causing adverse outcomes. In this prospective observational study, patients' first OPAT episodes, from initiation to completion, re-admission or early cessation, were recorded and analysed using Cox regression to identify factors associated with clinical deterioration leading to unplanned hospital re-admission. Of 2229 first episodes, 1874 (84.1%) completed treatment in OPAT as planned; 201 episodes (9.0%) were complicated by clinical deterioration and re-admitted. Other patients who failed to complete treatment were either re-admitted for elective procedures, experienced adverse drug reactions or peripherally inserted central catheter-related complications, or had other reasons for not completing treatment. Increased risk of clinical deterioration was associated with homecare OPAT (aHR=2.5, 95% CI 1.7-3.8; P<0.001), age >70 years (aHR=1.6, 95% CI 1.1-2.2; P=0.008) and non-private care (aHR=1.8, 95% CI 1.0-3.0; P=0.033). Diagnosis and type of antibiotic treatment were not significant risk factors for re-admission. OPAT provides intravenous antibiotics to those who would otherwise remain as hospital inpatients. In this large Asian cohort, clinical factors did not relate to the ability of patients to complete their treatment in OPAT. Criteria identified as significant warrant ongoing consideration as patients are assessed for acceptance into OPAT programmes.

Standardized outpatient management of Klebsiella pneumoniae liver abscesses.

OBJECTIVES: Community-acquired Klebsiella pneumoniae has emerged as a major cause of liver abscess in Asia. Using a standardized protocol, we conducted a prospective cohort study of all cases of K. pneumoniae liver abscess treated from 2005 to 2011 at two outpatient parenteral antimicrobial therapy (OPAT) centers in Singapore, to assess the safety and efficacy of treatment. METHODS: We included all OPAT eligible patients with radiologically confirmed (computed tomography or ultrasound) liver abscesses and K. pneumoniae-positive microbiological cultures obtained from abscess fluid and/or blood at two university teaching hospitals. The endpoints investigated were cure, clinical response, readmission, and mortality. RESULTS: All 109 patients enrolled in the study successfully completed treatment in OPAT. Nine patients required a short-term readmission due to clinical deterioration. There were no deaths or relapses at 30 days post cessation of antibiotics. Abscess size greater than 5 cm was associated with a delayed clinical response (odds ratio 5.34, 95% confidence interval 1.25-22.91, p = 0.02). CONCLUSION: The management of K. pneumoniae liver abscesses via OPAT using a standardized protocol is a safe and effective alternative to inpatient intravenous antibiotics.

Efficacy of continuous infusion of vancomycin for the outpatient treatment of methicillin-resistant Staphylococcus aureus infections.

OBJECTIVES: Recently published guidelines on the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections recommend against administering vancomycin by continuous infusion on the basis of insufficient studies comparing this with intermittent infusion. We compared outcomes of patients treated with continuous infusion and intermittent infusion of vancomycin. PATIENTS AND METHODS: Data for outpatients treated with continuous infusion and intermittent infusion of vancomycin were compared utilizing rates of clinical failure defined as the need for unplanned re-admission, change of antibiotics or extension of therapy. RESULTS: A total of 244 patients met the inclusion criteria, with 188 receiving continuous infusion and 56 intermittent infusion of vancomycin. The endpoint occurred in 21.3% and 30.4% of those receiving continuous infusion and intermittent infusion, respectively (relative risk 0.701, 95% CI 0.432-1.136, P = 0.159). Patient characteristics differed slightly between the two groups; however, logistic regression to adjust for differences in age, co-morbidity, subtherapeutic levels and prosthetic devices did not substantially alter this result. CONCLUSIONS: No difference in rates of clinical failure of continuous infusion and intermittent infusion of vancomycin was observed in this outpatient cohort.

Renal safety of tenofovir containing antiretroviral regimen in a Singapore cohort.

BACKGROUND: Tenofovirdisoproxilfumarate (TDF) is a nucleotide analogue widely recommended in international HIV treatment guidelines. The association of TDF and renal dysfunction has remained an area of interest. FINDINGS: We conducted a retrospective review of all patients on TDF from July 2007 to December 2009 in our institution and evaluated their renal function. Absolute change of creatinine clearance (CLCr) using Cockroft-Gault equation from baseline was calculated at 6, 12, 18 and 24 months. Overall, 226 patients were included in the study. Ninety percent were male. The median age was 46 yrs old (23-82), median weight was 60 kg (IQR 53.75-68), median CD4 count was 127 cells/mm3 (IQR 38-258) and median CLCr 82.7 mL/min (IQR 71.4-101.7) on initiation of TDF. The median decline of CLCr from baseline was -3.9 ml/min (IQR -12.3 to 7.6), and -3.6 ml/min (IQR -12.4 to 6.7) at 12 (n = 102), 24 months (n = 75) respectively. Eighteen of 226 patients had a decline in renal function to