Comparative outcomes of ?-lactam antibiotics in outpatient parenteral antibiotic therapy: treatment success, readmissions and antibiotic switches.
ABSTRACT: ?-Lactam antibiotics are commonly used in outpatient parenteral antimicrobial therapy (OPAT), but data regarding outcomes of long-term therapy are limited. The purpose of this study was to compare treatment success, readmission and antibiotic switch rates in patients treated with ?-lactam antibiotics as OPAT.We carried out a retrospective review of all patients, discharged from Tufts Medical Center with cefazolin, ceftriaxone, ertapenem or oxacillin, between January 2009 and June 2013. A competing risks analysis was used to compare the cumulative incidence of first occurrence of treatment success, antibiotic switch and 30 day readmission for each drug.Four hundred patients were identified (cefazolin n?=?38, ceftriaxone n?=?104, ertapenem n?=?128 and oxacillin n?=?130). Baseline demographics were similar. Treatment success rates were higher for ceftriaxone and ertapenem (cefazolin 61%, ceftriaxone 81%, ertapenem 73% and oxacillin 58%; P?
Project description:AbstractBackgroundOutpatient parenteral antimicrobial therapy (OPAT) has shifted from being a novel concept to an accepted model of care for some conditions. However, concerns remain that have limited its broader roll out: the use of daily ceftriaxone regarding its efficacy and impact on antibiotic resistance, intravenous (IV) catheter complications, risk of treating an acute infection directly from the emergency room (ER), and concern that OPAT has shifted the burden of cost from hospitals to patients. We aimed to address these questions with the first randomized controlled trial (RCT) of OPAT efficacy in children: comparing OPAT directly from the ER using IV ceftriaxone with hospitalization using IV flucloxacillin for moderate/severe cellulitis.MethodsThe RCT was set at a tertiary pediatric hospital from January 2015 to June 2017. Inclusion criteria: children 6 months–18 years with uncomplicated cellulitis needing IV antibiotics. Patients were randomized to ceftriaxone via OPAT at home or flucloxacillin in hospital, using a peripheral catheter. Primary outcome: treatment failure within 48 hours due to lack of improvement or adverse events. Secondary outcomes: complications, readmission, acquisition of nasal and stool-resistant bacteria and costs.ResultsA total of 188 children were randomized: 93 to OPAT and 95 to hospital. In the intention-to-treat population, there was no difference in treatment failure between OPAT and hospital (2% vs. 7%, 0.09). Per protocol, OPAT had less failure (1% vs. 8%, 0.03). There was no increased acquisition of MRSA, ESBL, VRE or with OPAT compared with in hospital at 1 week or 3 months ( 0.05). Complication rates were similar (6% vs. 7%, 0.78), and repeat IV catheterization was less with OPAT (3% vs. 15%, 0.002). Readmission was 1% on OPAT. The cost to families was significantly less with OPAT (AUD213 vs. AUD733, 0.001).ConclusionDespite the acuity of the infection, OPAT with IV ceftriaxone for moderate/severe cellulitis in children is efficacious with complications and readmissions no different from hospital care with IV flucloxacillin. Short-term ceftriaxone use in healthy children on OPAT is not associated with increased acquisition of resistant organisms, and has reduced burden of costs to families (ClinicalTrials.gov NCT02334124).Disclosures No reported disclosures.
Project description:A streamlined transition from inpatient to outpatient care can decrease 30-day readmissions. Outpatient parenteral antibiotic therapy (OPAT) programs have not reduced readmissions; an OPAT bundle has been suggested to improve outcomes. We implemented a transition-of-care (TOC) OPAT bundle and assessed the effects on all-cause, 30-day hospital readmission.Retrospectively, patients receiving postdischarge intravenous antibiotics were evaluated before and after implementation of a TOC-OPAT program in Bronx, New York, between July, 2015 and February, 2016. Pearson's ?2 test was used to compare 30-day readmissions between groups, and logistic regression was used to adjust for covariates. Time from discharge to readmission was analyzed to assess readmission risk, using log-rank test to compare survival curves and Cox proportional hazards model to adjust for covariates. Secondary outcomes, 30-day emergency department (ED) visits, and mortality were analyzed similarly.Compared with previous standard care (n = 184), the TOC-OPAT group (n = 146) had significantly lower 30-day readmissions before (13.0% vs 26.1%, P < .01) and after adjustment for covariates (odds ratio [OR] = 0.51; 95% confidence interval [CI], 0.27-0.94; P = .03). In time-dependent analyses, TOC-OPAT patients were at significantly lower risk for readmission (log-rank test, P < .01; hazard ratio = 0.56; 95% CI, 0.32-0.97; P = .04). Propensity-matched sensitivity analysis showed lower readmissions in the TOC-OPAT group (13.6% vs 24.6%, P = .04), which was attenuated after adjustment (OR = 0.51; 95% CI, 0.25-1.05; P = .07). Mortality and ED visits were similar in both groups.Our TOC-OPAT patients had reduced 30-day readmissions compared with the previous standard of care. An effective TOC-OPAT bundle can successfully improve patient outcomes in an economically disadvantaged area.
Project description:Objective:Beta-lactam antibiotics are recommended as first-line for treatment of methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia. The objective of this study was to compare effectiveness of anti-MSSA therapies among bacteremia patients exclusively exposed to 1 antimicrobial. Method:This was a national retrospective cohort study of patients hospitalized in Veterans Affairs medical centers with MSSA bacteremia from January 1, 2002, to October 1, 2015. Patients were included if they were treated exclusively with nafcillin, oxacillin, cefazolin, piperacillin/tazobactam, or fluoroquinolones (moxifloxacin and levofloxacin). We assessed 30-day mortality, time to discharge, inpatient mortality, 30-day readmission, and 30-day S. aureus reinfection. Hazard ratios (HRs) and 95% confidence intervals (CI) were calculated using propensity-score (PS) matched Cox proportional hazards regression model. Results:When comparing nafcillin/oxacillin (n = 105) with cefazolin (n = 107), 30-day mortality was similar between groups (PS matched n = 44; HR, 0.67; 95% CI, 0.11-4.00), as were rates of the other outcomes assessed. As clinical outcomes did not vary between nafcillin/oxacillin and cefazolin, they were combined for comparison with piperacillin/tazobactam (n = 113) and fluoroquinolones (n = 103). Mortality in the 30 days after culture was significantly lower in the nafcillin/oxacillin/cefazolin group compared with piperacillin/tazobactam (PS matched n = 48; HR, 0.10; 95% CI, 0.01-0.78), and similar when compared with fluoroquinolones (PS matched n = 32; HR, 1.33; 95% CI, 0.30-5.96). Conclusions:In hospitalized patients with MSSA bacteremia, no difference in mortality was observed between nafcillin/oxacillin and cefazolin or fluoroquinolones. However, higher mortality was observed with piperacillin/tazobactam as compared with nafcillin/oxacillin/cefazolin, suggesting it may not be as effective as a monotherapy in MSSA bacteremia.
Project description:BACKGROUND: Ertapenem is a once-a-day carbapenem and has excellent activity against many gram-positive and gram-negative aerobic, facultative, and anaerobic bacteria. The susceptibility of isolates of community-acquired bacteremia to ertapenem has not been reported yet. The present study assesses the in vitro activity of ertapenem against aerobic and facultative bacterial pathogens isolated from patients with community-acquired bacteremia by determining and comparing the MICs of cefepime, cefoxitin, ceftazidime, ceftriaxone, ertapenem, piperacillin, piperacillin-tazobactam, ciprofloxacin, amikacin and gentamicin. The prevalence of extended broad spectrum beta-lactamases (ESBL) producing strains of community-acquired bacteremia and their susceptibility to these antibiotics are investigated. METHODS: Aerobic and facultative bacteria isolated from blood obtained from hospitalized patients with community-acquired bacteremia within 48 hours of admission between August 1, 2004 and September 30, 2004 in Chang Gung Memorial Hospital at Keelung, Taiwan, were identified using standard procedures. Antimicrobial susceptibility was evaluated by Etest according to the standard guidelines provided by the manufacturer and document M100-S16 Performance Standards of the Clinical Laboratory of Standard Institute. Antimicrobial agents including cefepime, cefoxitin, ceftazidime, ceftriaxone, ertapenem, piperacillin, piperacillin-tazobactam, ciprofloxacin, amikacin and gentamicin were used against the bacterial isolates to test their MICs as determined by Etest. For Staphylococcus aureus isolates, MICs of oxacillin were also tested by Etest to differentiate oxacillin-sensitive and oxacillin-resistant S. aureus. RESULTS: Ertapenem was highly active in vitro against many aerobic and facultative bacterial pathogens commonly recovered from patients with community-acquired bacteremia (128/159, 80.5 %). Ertapenem had more potent activity than ceftriaxone, piperacillin-tazobactam, or ciprofloxacin against oxacillin-susceptible S. aureus (17/17, 100%)and was more active than any of these agents against enterobacteriaceae (82/82, 100%). CONCLUSION: Based on the microbiology pattern of community-acquired bacteremia, initial empiric treatment that requires coverage of a broad spectrum of both gram-negative and gram-positive aerobic bacteria, such as ertapenem, may be justified in moderately severe cases of community-acquired bacteremia in non-immunocompromised hosts.
Project description:This study investigates the evolution of an Escherichia coli sequence type 219 clone in a patient with recurrent urinary tract infection, comparing isolate EC974 obtained prior to antibiotic treatment and isolate EC1515 recovered after exposure to several ?-lactam antibiotics (ceftriaxone, cefixime, and imipenem). EC974 had a smooth colony morphology, while EC1515 had a rough colony morphology on sheep blood agar. RAPD-PCR analysis suggested that both isolates belonged to the same clone. Antimicrobial susceptibility tests showed that EC1515 was more resistant to piperacillin/tazobactam, cefepime, cefpirome, and ertapenem than EC974. Comparative genomic analysis was used to investigate the genetic changes of EC974 and EC1515 within the host, and showed three plasmids with replicons IncI1, P0111, and IncFII in both isolates. P0111-type plasmids pEC974-2 and pEC1515-2, contained the antibiotic resistance genes aadA2, tetA, and drfA12. IncFII-type plasmids pEC974-3 and pEC1515-3 contained the antibiotic resistance genes blaTEM-1, aadA1, aadA22, sul3, and inuF. Interestingly, blaCMY-111 and blaCMY-4 were found in very similar IncI1 plasmids that also contained aadA22 and aac(3)-IId, from isolates EC974 (pEC974-1) and EC1515 (pEC1515-1), respectively. The results showed in vivo amino acid substitutions converting blaCMY-111 to blaCMY-4 (R221W and A238V substitutions). Conjugation experiments showed a high frequency of IncI1 and IncFII plasmid co-transference. Transconjugants and DH5? cells harboring blaCMY-4 or blaCMY-111 showed higher levels of resistance to ampicillin, amoxicillin, cefazolin, cefuroxime, cefotaxime, cefixime, and ceftazidime, but not piperacillin/tazobactam, cefpime, or ertapenem. All known genes (outer membrane proteins and extended-spectrum AmpC ?-lactamases) involved in ETP resistance in E. coli were identical between EC974 and EC1515. This is the first study to identify the evolution of an IncI1 plasmid within the host, and to characterize blaCMY-111 in E. coli.
Project description:There is a dearth of guidance on the management of prosthetic joint infections (PJIs), in particular because of the lack of high-quality evidence for optimal antibiotics. Thus, we designed a nine-question survey of current practices and preferences among members of the Emerging Infections Network, a CDC-sponsored network of infectious diseases physicians, which was distributed in May 2012. In total, 556 (47.2%) of 1178 network members responded. As first-line antibiotic choice for MSSA PJI, 59% of responders indicated oxacillin/nafcillin, 33% cefazolin and 7% ceftriaxone; the commonest alternative was cefazolin (46%). For MRSA PJI, 90% preferred vancomycin, 7% daptomycin and 0.8% ceftaroline; the commonest alternative was daptomycin (65%). Antibiotic selection for coagulase-negative staphylococci varied depending on methicillin susceptibility. For staphylococcal PJIs with retained hardware, most providers would add rifampicin. Propionibacterium is usually treated with vancomycin (40%), penicillin (23%) or ceftriaxone (17%). Most responders thought 10-19% of all PJIs were culture-negative. Culture-negative PJIs of the lower extremities are usually treated with a vancomycin/fluoroquinolone combination, and culture-negative shoulder PJIs with vancomycin/ceftriaxone. The most cited criteria for selecting antibiotics were ease of administration and the safety profile. A treatment duration of 6-8 weeks is preferred (by 77% of responders) and is mostly guided by clinical response and inflammatory markers. Ninety-nine percent of responders recommend oral antibiotic suppression (for varying durations) in patients with retained hardware. In conclusion, there is considerable variation in treatment of PJIs both with identified pathogens and those with negative cultures. Future studies should aim to identify optimum treatment strategies.
Project description:BACKGROUND:The incidence and impact of adverse drug events (ADEs) leading to hospitalization and as a predominant risk factor for late graft loss has not been studied in transplantation. METHODS:This was a longitudinal cohort study of adult kidney recipients transplanted between 2005 and 2010 and followed through 2013. There were 3 cohorts: no readmissions, readmissions not due to an adverse drug event, and adverse drug events contributing to readmissions. The rationale of the adverse drug events contribution to the readmission was categorized in terms of probability, preventability, and severity. RESULTS:A total of 837 patients with 963 hospital readmissions were included; 47.9% had at least one hospital readmission and 65.0% of readmissions were deemed as having an ADE contribute. The predominant causes of readmissions related to ADEs included non-opportunistic infections (39.6%), opportunistic infections (10.5%), rejection (18.1%), and acute kidney injury (11.8%). Over time, readmissions due to under-immunosuppression (rejection) significantly decreased (-1.6% per year), while those due to over-immunosuppression (infection, cancer, or cytopenias) significantly increased (2.1% increase per year [difference 3.7%, P = .026]). Delayed graft function, rejection, creatinine, graft loss, and death were all significantly greater in those with an ADE that contributed to a readmission compared the other two cohorts (P < .05). CONCLUSION:These results demonstrate that ADEs may be associated with a significant increase in the risk of hospital readmission after kidney transplant and subsequent graft loss.
Project description:Teicoplanin possesses several convenient properties for use in the delivery of outpatient parenteral antimicrobial therapy (OPAT) services. However, its use is not widespread and data on its efficacy in the OPAT setting are limited. Here we present a case series of patients undergoing OPAT care being treated by either teicoplanin-based (n = 107) or ceftriaxone-based (n = 191) antibiotic regimens. Clinical failure with teicoplanin occurred in five episodes of care (4.7%) compared with only two episodes of ceftriaxone-based OPAT care (1.0%). Teicoplanin-associated clinical failure was observed in 2 (33.3%) of 6 patients with Enterococcus infections compared with 3 (3.0%) of 101 patients with non-Enterococcus infections. Overall, there were four (2.9%) drug-related adverse events for teicoplanin and four (1.8%) for ceftriaxone, prompting a switch to teicoplanin in three patients. These findings support the continued use of teicoplanin in OPAT as well as its consideration in centres where it is not currently being offered.
Project description:Background:To better monitor patients on outpatient parenteral antimicrobial therapy (OPAT), we need an improved understanding of risk factors for and timing of OPAT-associated adverse drug events (ADEs). Methods:We analyzed a prospective cohort of patients on OPAT discharged from 2 academic medical centers. Patients underwent chart abstraction and a telephone survey. Multivariable analyses estimated adjusted incident rate ratios (aIRR) between clinical and demographic risk factors and clinician-determined clinically significant ADEs. Descriptive data were used to present patient-reported ADEs. Results:Of 339 patients enrolled in the study, 18.0% experienced an ADE (N = 65), of which 49 were significant (14.5%, 2.24/1000 home-OPAT days). Patients with longer courses of therapy had lower rates of ADEs compared with patients treated for 0-13 days (14-27 days: aIRR, 0.44; 95% confidence interval [CI], 0.20-0.99; at least 28 days: aIRR, 0.11; 95% CI, 0.056-0.21). Risk factors for ADEs included female gender and receipt of daptomycin or vancomycin, while treatment for uncomplicated bacteremia and empiric treatment were associated with lower rates of ADEs. Conclusions:OPAT-related ADEs were common and often occurred within 2 weeks of hospital discharge. Patients on OPAT should be monitored more closely for ADEs, including clinical assessment and laboratory monitoring, especially within the first weeks after hospital discharge and particularly among women and patients who receive vancomycin.
Project description:We developed a rapid high-throughput PCR test and evaluated highly antibiotic-resistant clinical isolates of Escherichia coli (n?= 2,919), Klebsiella pneumoniae (n?= 1,974), Proteus mirabilis (n?= 1,150), and Pseudomonas aeruginosa (n?= 1,484) for several antibiotic resistance genes for comparison with phenotypic resistance across penicillins, cephalosporins, carbapenems, aminoglycosides, trimethoprim-sulfamethoxazole, fluoroquinolones, and macrolides. The isolates originated from hospitals in North America (34%), Europe (23%), Asia (13%), South America (12%), Africa (7%), or Oceania (1%) or were of unknown origin (9%). We developed statistical methods to predict phenotypic resistance from resistance genes for 49 antibiotic-organism combinations, including gentamicin, tobramycin, ciprofloxacin, levofloxacin, trimethoprim-sulfamethoxazole, ertapenem, imipenem, cefazolin, cefepime, cefotaxime, ceftazidime, ceftriaxone, ampicillin, and aztreonam. Average positive predictive values for genotypic prediction of phenotypic resistance were 91% for E. coli, 93% for K. pneumoniae, 87% for P. mirabilis, and 92% for P. aeruginosa across the various antibiotics for this highly resistant cohort of bacterial isolates.