Real-World Effectiveness of Intravenous and Oral Antibiotic Stepdown Strategies for Gram-Negative Complicated Urinary Tract Infection With Bacteremia.

Background: Robust data are lacking regarding the optimal route, duration, and antibiotic choice for gram-negative bloodstream infection from a complicated urinary tract infection source (GN-BSI/cUTI). Methods: In this multicenter observational cohort study, we simulated a 4-arm registry trial using a causal inference method to compare effectiveness of the following regimens for GN-BSI/cUTI: complete course of an intravenous ß-lactam (IVBL) or oral stepdown therapy within 7 days using fluoroquinolones (FQs), trimethoprim-sulfamethoxazole (TMP-SMX), or high-bioavailability ß-lactams (HBBLs). Adults treated between January 2016 and December 2022 for Escherichia coli or Klebsiella species GN-BSI/cUTI were included. Propensity weighting was used to balance characteristics between groups. The 60-day recurrence was compared using a multinomial Cox proportional hazards model with probability of treatment weighting. Results: Of 2571 patients screened, 759 (30%) were included. Characteristics were similar between groups. Compared with IVBLs, we did not observe a difference in effectiveness for FQs (adjusted hazard ratio, 1.09 [95% confidence interval, .49-2.43]) or TMP-SMX (1.44 [.54-3.87]), and the effectiveness of TMP-SMX/FQ appeared to be optimal at durations of >10 days. HBBLs were associated with nearly 4-fold higher risk of recurrence (adjusted hazard ratio, 3.83 [95% confidence interval, 1.76-8.33]), which was not mitigated by longer treatment durations. Most HBBLs (67%) were not optimally dosed for bacteremia. Results were robust to multiple sensitivity analyses. Conclusions: These real-world data suggest that oral stepdown therapy with FQs or TMP-SMX have similar effectiveness as IVBLs. HBBLs were associated with higher recurrence rates, but dosing was suboptimal. Further data are needed to define optimal dosing and duration to mitigate treatment failures.

Oral ß-Lactams, Fluoroquinolones, or Trimethoprim-Sulfamethoxazole for Definitive Treatment of Uncomplicated Escherichia coli or Klebsiella Species Bacteremia From a Urinary Tract Source.

Background: Fluoroquinolones (FQs) are effective for oral step-down therapy for gram-negative bloodstream infections but are associated with unfavorable toxic effects. Robust data are lacking for trimethoprim-sulfamethoxazole (TMP-SMX) and high-bioavailability ß-lactams (HBBLs). Methods: In this multicenter observational cohort study, we simulated a 3-arm registry trial using causal inference methods to compare the effectiveness of FQs, TMP-SMX, or HBBLs for gram-negative bloodstream infections oral step-down therapy. The study included adults treated between January 2016 and December 2022 for uncomplicated Escherichia coli or Klebsiella species bacteremia of urinary tract origin who were who were transitioned to an oral regimen after ≤4 days of effective intravenous antibiotics. Propensity weighting was used to balance characteristics between groups. 60-day recurrence was compared using a multinomial Cox proportional hazards model with probability of treatment weighting. Results: Of 2571 patients screened, 648 (25%) were included. Their median age (interquartile range) was 67 (45-78) years, and only 103 (16%) were male. Characteristics were well balanced between groups. Compared with FQs, TMP-SMX had similar effectiveness (adjusted hazard ratio, 0.91 [95% confidence interval, .30-2.78]), and HBBLs had a higher risk of recurrence (2.19 [.95-5.01]), although this difference was not statistically significant. Most HBBLs (70%) were not optimally dosed for bacteremia. A total antibiotic duration ≤8 days was associated with a higher recurrence rate in select patients with risk factors for failure. Conclusions: FQs and TMP-SMX had similar effectiveness in this real-world data set. HBBLs were associated with higher recurrence rates but suboptimal dosing may have contributed. Further studies are needed to define optimal BL dosing and duration to mitigate treatment failures.

Outcomes of patients with bacteriuria/pyuria of clinically undetermined significance (BPCUS) treated with antibiotics in 23 community hospital emergency departments.

The optimal management of bacteriuria/pyuria of clinically undetermined significance (BPCUS) is unknown. Among 220 emergency department patients prescribed antibiotics for BPCUS, we found frequent readmissions, which were mitigated by outpatient follow-up visits. Observation and follow-up for an unknown diagnosis should be emphasized over antibiotics due to high likelihood of readmissions.

Impact of a Multifaceted Intervention on Antibiotic Prescribing for Cystitis and Asymptomatic Bacteriuria in 23 Community Hospital Emergency Departments.

Background: Urinary tract infections (UTIs) are over-diagnosed and over-treated in the emergency department (ED) leading to unnecessary antibiotic exposure and avoidable side effects. However, data describing effective large-scale antimicrobial stewardship program (ASP) interventions to improve UTI and asymptomatic bacteriuria (ASB) management in the ED are lacking. Methods: We implemented a multifaceted intervention across 23 community hospital EDs in Utah and Idaho consisting of in-person education for ED prescribers, updated electronic order sets, and implementation/dissemination of UTI guidelines for our healthcare system. We compared ED UTI antibiotic prescribing in 2021 (post-intervention) to baseline data from 2017 (pre-intervention). The primary outcomes were the percent of cystitis patients prescribed fluoroquinolones or prolonged antibiotic durations (>7 days). Secondary outcomes included the percent of patients treated for UTI who met ASB criteria, and 14-day UTI-related readmissions. Results: There was a significant decrease in prolonged treatment duration for cystitis (29% vs 12%, P < .01) and treatment of cystitis with a fluoroquinolone (32% vs 7%, P < .01). The percent of patients treated for UTI who met ASB criteria did not change following the intervention (28% pre-intervention versus 29% post-intervention, P = .97). A subgroup analysis indicated that ASB prescriptions were highly variable by facility (range 11%-53%) and provider (range 0%-71%) and were driven by a few high prescribers. Conclusions: The intervention was associated with improved antibiotic selection and duration for cystitis, but future interventions to improve urine testing and provide individualized prescriber feedback are likely needed to improve ASB prescribing practice.

Effect of tele-COVID rounds and a tele-stewardship intervention on antibiotic use in COVID-19 patients admitted to 17 small community hospitals.

Antibiotic stewardship interventions are urgently needed to reduce antibiotic overuse in hospitalized COVID-19 patients, particularly in small community hospitals (SCHs), who often lack access to infectious diseases (ID) and stewardship resources. We implemented multidisciplinary tele-COVID rounds plus tele-antibiotic stewardship surveillance in 17 SCHs to standardize COVID management and evaluate concurrent antibiotics for discontinuation. Antibiotic use was compared in the 4 months preintervention versus 10 months postintervention. Interrupted time-series analysis demonstrated an immediate decrease in antibiotic use by 339 days of therapy/1000 COVID-19 patient days (p < .001), and an estimated 5258 antibiotic days avoided during the postintervention period. Thirty-day mortality was not significantly different, and a significant reduction in transfers was observed following the intervention (23.3% vs. 7.8%, p < .001). A novel tele-ID and tele-stewardship intervention significantly decreased antibiotic use and transfers among COVID-19 patients at 17 SCHs, demonstrating that telehealth is a feasible way to provide ID expertise in community and rural settings.

An Implementation Roadmap for Establishing Remote Infectious Disease Specialist Support for Consultation and Antibiotic Stewardship in Resource-Limited Settings.

Infectious Disease (ID)-trained specialists, defined as ID pharmacists and ID physicians, improve hospital care by providing consultations to patients with complicated infections and by leading programs that monitor and improve antibiotic prescribing. However, many hospitals and nursing homes lack access to ID specialists. Telehealth is an effective tool to deliver ID specialist expertise to resource-limited settings. Telehealth services are most useful when they are adapted to meet the needs and resources of the local setting. In this step-by-step guide, we describe how a tailored telehealth program can be implemented to provide remote ID specialist support for direct patient consultation and to support local antibiotic stewardship activities. We outline 3 major phases of putting a telehealth program into effect: pre-implementation, implementation, and sustainment. To increase the likelihood of success, we recommend actively involving local leadership and other stakeholders in all aspects of developing, implementing, measuring, and refining programmatic activities.

A Fully Integrated Infectious Diseases and Antimicrobial Stewardship Telehealth Service Improves Staphylococcus aureus Bacteremia Bundle Adherence and Outcomes in 16 Small Community Hospitals.

Background: Infectious diseases (ID) and antimicrobial stewardship (AS) improve Staphylococcus aureus bacteremia (SAB) outcomes. However, many small community hospitals (SCHs) lack on-site access to these services, and it is not known if ID telehealth (IDt) offers the same benefit for SAB. We evaluated the impact of an integrated IDt service on SAB outcomes in 16 SCHs. Methods: An IDt service offering IDt physician consultation plus IDt pharmacist surveillance was implemented in October 2016. Patients treated for SAB in 16 SCHs between January 2009 and August 2019 were identified for review. We compared SAB bundle adherence and outcomes between patients with and without an IDt consult (IDt group and control group, respectively). Results: A total of 423 patients met inclusion criteria: 157 in the IDt group and 266 in the control group. Baseline characteristics were similar between groups. Among patients completing their admission at an SCH, IDt consultation increased SAB bundle adherence (79% vs 23%; odds ratio [OR], 16.9; 95% CI, 9.2-31.0). Thirty-day mortality and 90-day SAB recurrence favored the IDt group, but the differences were not statistically significant (5% vs 9%; P = .2; and 2% vs 6%; P = .09; respectively). IDt consultation significantly decreased 30-day SAB-related readmissions (9% vs 17%; P = .045) and increased length of stay (median [IQR], 5 [5-8] days vs 5 [3-7] days; P = .04). In a subgroup of SAB patients with a controllable source, IDt appeared to have a mortality benefit (2% vs 9%; OR, 0.12; 95% CI, 0.01-0.98). Conclusions: An integrated ID/AS telehealth service improved SAB management and outcomes at 16 SCHs. These findings provide important insights for other IDt programs.

No Implementation Without Representation: Real-Time Pharmacist Intervention Optimizes Rapid Diagnostic Tests for Bacteremia at a Small Community Hospital.

Background: Rapid diagnostic tests (RDTs) for bacteremia allow for early antimicrobial therapy modification based on organism and resistance gene identification. Studies suggest patient outcomes are optimized when infectious disease (ID)-trained antimicrobial stewardship personnel intervene on RDT results. However, data are limited regarding RDT implementation at small community hospitals, which often lack access to on-site ID clinicians. Methods: This study evaluated the impact of RDTs with and without real-time pharmacist intervention (RTPI) at a small community hospital with local pharmacist training and asynchronous support from a remote ID Telehealth pharmacist. Time to targeted therapy (TTT) in patients with bacteremia was compared retrospectively across 3 different time periods: a control without RDT, RDT-only, and RDT with RTPI. Results: Median TTT was significantly faster in both the RDT with RTPI and RDT-only groups compared with the control group (2 vs 25 vs 51 hours respectively; P < .001). TTT was numerically faster for RDT with RTPI compared with RDT-only but did not reach statistical significance (P = .078). Median time to any de-escalation was significantly shorter for RDT with RTPI compared with both RDT-only (14 vs 33 hours; P = .012) and the control group (14 vs 45 hours; P < .001). Median length of stay was also significantly shorter in both RDT groups compared with the control group (4.0 vs 4.1 vs 5.5 hours; P = .013). Conclusion: This study supports RDT use for bacteremia in a small community hospital with ID Telehealth support, suggesting additional benefit with RTPI.

Implementation of an Infectious Diseases Telehealth Consultation and Antibiotic Stewardship Program for 16 Small Community Hospitals.

BACKGROUND: Telehealth improves access to infectious diseases (ID) and antibiotic stewardship (AS) services in small community hospitals (SCHs), but the optimal model has not been defined. We describe implementation and impact of an integrated ID telehealth (IDt) service for 16 SCHs in the Intermountain Healthcare system. METHODS: The Intermountain IDt service included a 24-hour advice line, eConsults, telemedicine consultations (TCs), daily AS surveillance, long-term AS program (ASP) support by an IDt pharmacist, and a monthly telementoring webinar. We evaluated program measures from November 2016 through April 2018. RESULTS: A total of 2487 IDt physician interactions with SCHs were recorded: 859 phone calls (35% of interactions), 761 eConsults (30%), and 867 TCs (35%). Of 1628 eConsults and TCs, 1400 (86%) were SCH provider requests, while 228 (14%) were IDt pharmacist generated. Six SCHs accounted for >95% of interactions. Median consultation times for each initial telehealth interaction type were 5 (interquartile range [IQR], 5-10) minutes for phone calls, 20 (IQR, 15-25) minutes for eConsults, and 50 (IQR, 35-60) minutes for TCs. Thirty-two percent of consults led to in-person ID clinic follow-up. Bacteremia was the most common reason for consultation (764/2487 [31%]) and Staphylococcus aureus the most common organism identified. ASPs were established at 16 facilities. Daily AS surveillance led to 2229 SCH pharmacist and 1305 IDt pharmacist recommendations. Eight projects were completed with IDt pharmacist support, leading to significant reductions in meropenem, vancomycin, and fluoroquinolone use. CONCLUSIONS: An integrated IDt model led to collaborative ID/ASP interventions and improvements in antibiotic use at 16 SCHs. These findings provide insight into clinical and logistical considerations for IDt program implementation.

Pharmacokinetics and Pharmacodynamics of High-Dose Piperacillin-Tazobactam in Obese Patients.

BACKGROUND AND OBJECTIVE: Standard piperacillin-tazobactam (P-T) dosing may be suboptimal in obesity, but high-dose regimens have not been studied. We prospectively evaluated the pharmacokinetics and pharmacodynamics of standard- and high-dose P-T in obese adult inpatients. METHODS: Those receiving standard-dose P-T with BMI ≥ 30 kg/m2 weighing 105-139 kg or ≥ 140 kg were given up to 6.75 g or 9 g every 6 h, respectively. Patients were monitored closely for safety. Elimination phase blood samples were drawn for 28 patients on standard and high doses to calculate the pharmacokinetic values using a one-compartment model. The likelihood of pharmacodynamic target attainment (100% fT > 16/4 mg/L) on various P-T regimens was calculated using each patient's own pharmacokinetic values. RESULTS: Piperacillin and tazobactam half-lives ranged from 0.5-10.6 to 0.9-15.0 h, while volumes of distribution ranged from 13.6-54.8 to 11.5-60.1 L, respectively. Predicted dose requirements for target attainment ranged from 2.25 g every 6 h in hemodialysis patients to a 27 g/24-h continuous infusion in a patient with a short P-T half-life. An amount of 4.5 g every 6 h would have met the target for only 1/12 (8%) patients with creatinine clearance ≥ 80 mL/min and 13/28 (46%) for all enrolled patients. One patient (3%) experienced an adverse event deemed probably related to high-dose P-T. CONCLUSION: Some patients required high P-T doses for target attainment, but dosing requirements were highly variable. Doses up to 6.75 g or 9 g every 6 h may be tolerable; however, studies are needed to see if high dosing, prolonged infusions, or real-time therapeutic drug monitoring improves outcomes in obese patients. CLINICAL TRIAL REGISTRATION (CLINICALTRIALS.GOV): NCT01923363.

Antibiotic prescribing for adult bacteriuria and pyuria in community hospital emergency departments.

OBJECTIVE: To describe emergency department (ED) antibiotic prescribing for urinary tract infections (UTIs) and asymptomatic bacteriuria (ASB) and to identify improvement opportunities. METHODS: Patients treated for UTI in 16 community hospital EDs were reviewed to identify prescribing that was unnecessary (any treatment for ASB, duration >7 days for cystitis or >14 days for pyelonephritis) or suboptimal [ineffective antibiotics (nitrofurantoin/fosfomycin) or duration <7 days for pyelonephritis]. Duration criteria were based on recommendations for complicated UTI since criteria for uncomplicated UTI were not reviewed. 14-day repeat ED visits were evaluated. RESULTS: Of 250,788 ED visits, UTI was diagnosed in 13,466 patients (5%), and 1427 of these (11%) were manually reviewed. 286/1427 [20%, 95% CI: 18-22%] met criteria for ASB and received 2068 unnecessary antibiotic days [mean (±SD) 7 (2) days]. Mean treatment duration was 7 (2) days for cystitis and 9 (2) days for pyelonephritis. Of 446 patients with cystitis, 128 (29%) were prescribed >7 days (total 396 unnecessary). Of 422 pyelonephritis patients, 0 (0%) were prescribed >14 days, 20 (5%) were prescribed <7 days, and 9 (2%) were given ineffective antibiotics. Overall, prescribing was unnecessary or suboptimal in 443/1427 [31%, 95% CI: 29-33%] resulting in 2464/11,192 (22%) unnecessary antibiotic days and 8 (0.5%) preventable ED visits. CONCLUSIONS: Among reviewed patients, poor UTI prescribing in 16 EDs resulted in unnecessary antibiotic days and preventable readmissions. Key areas for improvement include non-treatment of ASB and shorter durations for cystitis.

Antimicrobial Stewardship in Community Hospitals.

Antibiotic stewardship programs are needed in all health care facilities, regardless of size and location. Community hospitals that have fewer resources may have different priorities and require different strategies when defining antibiotic stewardship program components and implementing interventions. By following the Centers for Disease Control and Prevention Core Elements and using the strategies suggested in this article, readers should be able to design, develop, participate in, or improve antibiotic stewardship programs within community hospitals.

Individualized Pharmacokinetic Dosing of Vancomycin Reduces Time to Therapeutic Trough Concentrations in Critically Ill Patients.

Dosing vancomycin in critically ill patients often results in subtherapeutic and supratherapeutic trough concentrations. In this retrospective study, we compared the time to goal trough attainment and incidence of acute kidney injury in intensive care unit (ICU) patients whose vancomycin was dosed by a pharmacy pharmacokinetic (PK) dosing and monitoring service to the standard of care. Three-hundred fifty adult ICU patients at a Level 1 trauma, teaching hospital who received vancomycin for >24 hours from February 1, 2016, to November 30, 2016, were screened. Patients were included in the PK group if consecutive serum concentrations were used to calculate individualized PK and determine a dosing regimen. Patients who were dosed using troughs only were then matched 1-to-1 to the PK group by date of vancomycin initiation and included in the traditional group. Fifty patients were included in each group. Baseline characteristics were similar, except the PK group had more patients under the care of the neuromedical ICU service (42% vs 18%; P = .02) and fewer patients with a corrected creatinine clearance <30 mL/min/1.73 m2 (22% vs 46%; P = .02). Attainment of goal trough concentrations for the PK and traditional groups were 84.4% and 29.4% by 48 hours (P = .0001), 88.4% and 60.7% by 72 hours (P = .009), and 92.9% and 77.8% by 96 hours (P = .1), respectively. Incidence of acute kidney injury between the PK and traditional groups was not statistically significant (8.3% vs 14%; P = .5). Utilization of individualized pharmacokinetic dosing of vancomycin in critically ill patients resulted in faster goal trough attainment without an increase in nephrotoxicity.

Use of Individual Pharmacokinetics to Improve Time to Therapeutic Vancomycin Trough in Pediatric Oncology Patients.

OBJECTIVE: Optimization of vancomycin dosing is difficult in children, given rapid drug clearance and patient heterogeneity. We sought to evaluate the impact of dosing using individual pharmacokinetic parameters on time to goal trough concentration in pediatric oncology patients. METHODS: A retrospective review was conducted to assess vancomycin dosing in the pediatric oncology unit at Loma Linda University Children's Hospital between January 2013 and August 2013 (standard dosing group [SDG]). These patients were compared to those in a prospective arm that used pharmacokinetic dosing (pharmacokinetic dosing group [PKG]) between March 2014 and May 2015. Outcomes included percent of patients reaching a target trough by the specified time points, number of dose adjustments, number of serum concentrations drawn, and number of patients with supratherapeutic troughs. RESULTS: Of 35 patients meeting inclusion criteria for the SDG, 2 (5.7%) reached goal trough concentration by 48 hours, compared with 14 of 16 patients (87%) in the PKG (p = 0.0001). Significantly more patients reached their goal trough at each time point in the PKG. There was no difference in number of dose adjustments, but significantly more concentrations were drawn on average in the PKG (mean, 4.6 versus 3.1, p = 0.02). In the SDG and PKG, respectively, 1 patient and 3 patients had supratherapeutic trough concentrations (p = 0.09). CONCLUSIONS: Dosing using individual pharmacokinetic parameters led to a significant reduction in time to attain the desired vancomycin trough concentration in our pediatric oncology patients. Given the wide variation in dose requirements in this and other studies, application of patient-specific pharmacokinetics is essential to optimize vancomycin dosing in pediatric patients.

Outcomes of Vancomycin plus a ß-Lactam versus Vancomycin Only for Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia.

The objective of this retrospective study was to compare the rates of treatment failure, which was a composite of clinical and microbiologic failure, of patients receiving vancomycin and a ß-lactam to those receiving vancomycin only for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Patients 16 to 89 years of age with MRSA bacteremia admitted to a university-affiliated hospital from 1 January 2014 to 31 December 2016 were screened for study inclusion. Patients were eligible if they received >48 h of vancomycin and a ß-lactam (combination group) or vancomycin only (standard group) within 48 h after bacteremia onset. A total of 182 patients were screened: 47 were included in the standard group, and 63 were in the combination group. The combination group had a higher baseline body mass index (29.2 ± 8.0 kg/m2 versus 25.8 ± 7.1 kg/m2, P = 0.022), acute physiologic assessment and chronic health evaluation-II (APACHE-II) score (median [interquartile range], 21 [15 to 26] versus 16 [10 to 22], P = 0.003), and incidence of septic shock (31.8% versus 14.9%, P = 0.047). Using multivariate analysis, combination therapy was the only variable that decreased treatment failures (odds ratio [95% confidence interval], 0.337 [0.142 to 0.997]), while vancomycin MIC > 1 mg/liter and male gender increased treatment failures (4.018 [1.297 to 12.444] and 2.971 [1.040 to 8.488], respectively). The 30-day mortality rates (15.0% versus 14.9%, P = 1.000) and the incidence of adverse drug events (19.1% versus 23.4%, P = 0.816) were not statistically different between the combination and standard groups. Combination therapy of vancomycin with a ß-lactam led to significantly fewer treatment failures than vancomycin monotherapy for MRSA bacteremia.

Pharmacokinetics of Ceftazidime-Avibactam in Two Patients With KPC-Producing Klebsiella pneumoniae Bacteremia and Renal Impairment.

Limited data exist regarding optimal dosing of ceftazidime/avibactam (C/A) in patients with unique physiology, who were excluded from published clinical trials. Data are also lacking regarding clinical efficacy of C/A in patients with infections due to multidrug-resistant gram-negative pathogens. To expand knowledge in these areas, we present pharmacokinetic data from two patients with Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae bloodstream infections, both of whom had renal impairment, and one of whom was morbidly obese. C/A was initiated in both patients at higher doses than those recommended in the package insert. To assess adequacy of dosing at steady state, a trough was drawn before and consecutive levels were drawn after a C/A dose such that half-life and volume of distribution for ceftazidime and avibactam could be calculated using the Sawchuk-Zaske method. Both patients cleared their bloodstream infection without evidence of toxicity. Patient 1 and patient 2 had prolonged half-lives for ceftazidime (22.8 and 14.5 hours, respectively) and avibactam (19.6 and 11.3 hours, respectively). Both patients had volumes of distribution significantly larger than those listed in the package insert: ceftazidime 47.1 L and 24.7 L and avibactam 50.3 L and 38.7 L for patients 1 and 2, respectively. Considering the larger volumes of distribution and levels observed in our patients, recommended doses and intervals may not be sufficient for obese patients with renal failure, especially for those infected with KPC-producing organisms. Additional efficacy and pharmacokinetic data are still needed for this agent to define optimal dosing strategies in patients commonly encountered in clinical practice.

A simple and rapid RP-HPLC method for the simultaneous determination of piperacillin and tazobactam in human plasma.

A rapid and sensitive reverse phase HPLC (RP-HPLC) method for the simultaneous quantitation of piperacillin and tazobactam in human plasma has been developed and validated. The method utilizes a novel, simple and rapid solid phase extraction step, which results in an improved extraction yield of analytes from human plasma, as well as significantly reduced interference from serum components at low UV wavelength detection compared to previously published liquid-liquid extraction methods. Chromatographic separation was carried out on a Hypersil ODS C18, 3µm column using an acetonitrile-trifluoroacetic acid-water gradient elution with dual wavelength quantitation at 254nm for piperacillin and 218nm for tazobactam. Linear relationships between peak area and drug concentration were obtained in the range of 1.0-200µg/mL for piperacillin and 0.78-50µg/mL for tazobactam, with r2=0.9997 and 0.9994 respectively. The assay proved to be sensitive (with a lower limit of quantitation of 1µg/mL for piperacillin and 0.78µg/mL for tazobactam), specific (no interference from plasma components at either 218nm or 254nm), and reproducible (both intra- and inter- day coefficients of variation were ≤6%). With a total process/assay time of less than 30min, the method provides a simple, precise and reproducible assay for monitoring piperacillin and tazobactam plasma levels that can be readily adapted for routine clinical use.

Ertapenem-Induced Hallucinations and Delirium in an Elderly Patient.

OBJECTIVE: To report a case of ertapenem-induced hallucinations and delirium in an elderly, morbidly obese patient. SETTING/PRACTICE DESCRIPTION: A 71-year-old male was receiving intravenous antibiotics at an outside nursing facility through our Outpatient Parenteral Antimicrobial Therapy (OPAT) program, which has enrolled more than 800 patients since 2009. He was admitted to our medical center, a 673-bed tertiary health care facility, which provides care to more than 100,000 veterans in Northeast Ohio. MAIN OUTCOME/RESULTS: Our patient was admitted with an acute heart failure exacerbation after being discharged four weeks prior with a plan to complete six weeks of intravenous daptomycin 1 g daily and ertapenem 1 g daily for a left-calcaneal diabetic foot osteomyelitis. On initial exam, in addition to volume overload, he was noted to have fluctuating orientation, hallucinations, and suicidal ideations, which were all a significant change from his baseline mentation. A physical, laboratory, and radiologic workup revealed no conclusive etiology for his symptoms, at which point drug-induced toxicity was suspected. Upon discontinuation of ertapenem, the patient rapidly improved over the next 72 hours, including return to baseline mentation and absence of any suicidal thoughts. Use of the Naranjo probability scale indicated a probable relationship between ertapenem and the adverse effects experienced by our patient. CONCLUSION: This case report and literature review demonstrates the potential severity of non-seizure-related neurotoxicity associated with ertapenem. As this toxicity can be life-threatening if unrecognized, it is crucial that clinicians across all practice settings be proactive in detecting and preventing it.