Stevens, Ryan W.

Abstract Background Fluoroquinolones (FQs) are known to be accompanied by significant risks. However, the incidence of adverse events (ADEs) resulting in unplanned drug discontinuation when used for periprosthetic joint infections (PJIs) is currently unknown. Methods This study included 156 patients over the age of 18 treated for staphylococcal PJI with debridement, antibiotics, and implant retention between 1 January 2007 and 21 November 2019. Of the 156 patients, 64 had total hip arthroplasty (THA) and 92 had total knee arthroplasty (TKA) infections. The primary outcome was rate of unplanned drug discontinuation. Secondary outcomes included incidence of severe ADEs, unplanned rifamycin discontinuation, mean time to unplanned regimen discontinuation, and all-cause mortality. Results Overall, unplanned drug discontinuation occurred in 35.6% of patients in the FQ group and 3% of patients in the non-FQ group. The rate of unplanned discontinuation of FQ regimens as compared with non-FQ regimens was 27.5% vs 4.2% (P = .021) in THA infections and 42% vs 2.4% (P < .001) in TKA infections. There was no significant difference in severe ADEs between FQ and non-FQ regimens in both THA and TKA infections. The overall rate of nonsevere ADEs in FQ compared with non-FQ regimens was 43.3% vs 6.1% (P < .001). FQs were associated with tendinopathy, myalgia, arthralgia, and nausea. Conclusions A significantly higher rate of unplanned drug discontinuation was associated with FQ as compared with non-FQ regimens. This provides a real-world view of the implications of FQ-related ADEs on unplanned discontinuation when used in prolonged durations for the management of staphylococcal PJIs.

Abstract Background The use of extracorporeal membrane oxygenation (ECMO) in critically ill adults is increasing. There are currently no guidelines for antimicrobial prophylaxis. We analyzed 7 years of prophylactic antimicrobial use across 3 time series for patients on ECMO at our institution in the development, improvement, and streamlining of our ECMO antimicrobial prophylaxis protocol. Methods In this quasi-experimental interrupted time series analysis, we evaluated the impact of an initial ECMO antimicrobial prophylaxis protocol, implemented in 2014, on antimicrobial use and National Healthcare Safety Network–reportable infection rates. Then, following a revision and streamlining of the protocol in November 2018, we reevaluated the same metrics. Results Our study population included 338 intensive care unit patients who received ECMO between July 2011 and November 2019. After implementation of the first version of the protocol, we did not observe significant changes in antimicrobial use or infection rates in these patients; however, following revision and streamlining of the protocol, we demonstrated a significant reduction in broad-spectrum antimicrobial use for prophylaxis in patients on ECMO without any evidence of a compensatory increase in infection rates. Conclusions Our final protocol significantly reduces broad-spectrum antimicrobial use for prophylaxis in patients on ECMO. We propose a standard antimicrobial prophylaxis regimen for patients on ECMO based on current evidence and our experience. Summary: There are no guidelines for antimicrobial prophylaxis in patients on extracorporeal membrane oxygenation (ECMO). A rational approach employing concepts of antimicrobial stewardship can drive logical antimicrobial selection for prophylaxis in patients on ECMO without adversely impacting outcomes.

Abstract Background Omadacycline (OMC) is an aminomethylcycline antibiotic in the tetracycline class that has been Food and Drug Administration-approved for acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. OMC has been shown to have potent in vitro activity against a broad-spectrum of Gram-positive and Gram-negative organisms, as well as Nontuberculous Mycobacteria (NTM). Due to it’s unique activity and availability as an oral agent, off-label use of OMC has been increasing. We evaluated the real-world effectiveness and safety of OMC for a variety of infections. Methods This was a multicenter, retrospective, observational study that was conducted from January 2020 to June 2020. We included all patients ≥ 18 years of age that received OMC for ≥ 72 hours for any indication and/or pathogen. The primary outcome was clinical success, defined as a lack of 30-day (non-NTM) or 90-day (NTM) mortality or microbiologic recurrence and absence of therapy escalation or alteration. Reasons for OMC utilization and incidence of potential adverse effects attributable to OMC were also analyzed. Results A total of 18 patients were included from six geographically distinct academic health systems (median age: 56 (IQR, 49-60.5) years; 61% male; 72% Caucasian). The majority of OMC use was in NTM (61%; 100% Mycobacterium abscessus) and in Acinetobacter baumannii (22%) for bone/joint (39%) and respiratory tract (33%) infections. OMC was used primarily in the outpatient setting alone (83%) and most isolates did not have OMC susceptibility conducted (89%). Clinical success was reported in 83% of the total population (71% non-NTM and 91% NTM). The majority of patients were prescribed OMC due to antimicrobial resistance to previous antibiotic(s) (61%) and/or due to OMC’s availability as an oral agent (44%). Three patients experienced side effects while on therapy (serum creatinine elevation, AST/ALT increase, and gastrointestinal distress). Conclusion OMC appears to be effective and well-tolerated for a variety of infections caused by various pathogens, including M. abscessus and A. baumannii. Disclosures Michael J. Rybak, PharmD, MPH, PhD, Paratek (Grant/Research Support)

The use of the kidney function biomarker cystatin C (cysC) can improve the accuracy of vancomycin dosing for target trough attainment in nonobese patients. It is unknown whether cysC can also improve vancomycin target trough attainment in overweight and obese patients. We conducted a retrospective observational study of overweight or obese hospitalized adults with stable renal function administered intravenous vancomycin between January 2011 and July 2019. Linear regression models were used to predict initial steady-state vancomycin troughs using several factors, including various cysC- and serum creatinine (SCr)-based estimates of kidney function.

AbstractIn an effort to “flatten the curve” of SARS-CoV-2, society is urged to practice social distancing. However, the management of other disease states may require some patients to undergo outpatient parenteral antimicrobial therapy (OPAT). Practical considerations for OPAT management during an infectious pandemic are reviewed. These include shortening durations of therapy, utilizing the oral route, avoiding medications requiring therapeutic drug monitoring, selecting antimicrobials with long durations, decreasing frequency of laboratory blood draws, and performing tele-health visits.

Abstract Purpose A case of vancomycin enzyme immunoassay (EIA) interference confirmed by high-performance liquid chromatography (HPLC) is described. Summary Therapeutic drug monitoring is standard of practice in vancomycin dosing and monitoring in order to maximize the pharmacodynamic effects and minimize toxicity. After a 52-year-old woman received 5 doses of vancomycin, serum concentrations continued to rise for several days in the absence of ongoing vancomycin administration. Despite persistently elevated vancomycin concentrations, the patient clinically deteriorated and required treatment with an alternative agent. Subsequently, serum concentrations were processed via HPLC and analyzed for percent protein binding. Confirmatory analysis revealed substantially lower concentrations by HPLC than were obtained by EIA and an abnormal elevation in protein binding. After discharge from the index admission, the patient returned 11 months later and had a dectectable vancomycin concentration by EIA prior to receipt of vancomycin. HPLC analysis confirmed the true concentration was undetectable. Though the exact interfering substance was not identified, the above discrepancy in concentrations between the two assay methods indicates the presence of assay interference, and adds to the available literature suggesting similar occurrences. This case is particularly troubling given that the level of interference was not such that it would lead a clinician to immediately suspect interference, and the patient experienced treatment failure. Conclusion Falsely elevated values for serum vancomycin concentration, measured by EIA, contributed to treatment failure in a patient. The substance presumably responsible for EIA interferences was not identified.

Multidrug‐resistant (MDR) Pseudomonas aeruginosa infections often represent a therapeutic challenge requiring utilization of older, more toxic antibiotics, or new agents with limited data. Once susceptibility to β‐lactam and fluoroquinolone antibiotics has been lost, other therapeutic options such as aminoglycoside or polymyxin antibiotics carry significant adverse effects such as nephrotoxicity, neurotoxicity, and ototoxicity. A novel cephalosporin, cefiderocol, lacks gram‐positive and anaerobic activity but offers broad coverage of gram‐negative bacteria, including P. aeruginosa . A unique catechol side chain gives it activity as a siderophore, thereby increasing bacterial uptake and decreasing efflux. Additionally, cefiderocol is stable against a wide array of β‐lactamases. Despite these promising characteristics, there are minimal data currently available in the literature detailing the use of cefiderocol in the treatment of MDR P. aeruginosa infections. We present a case of a 46‐year‐old man who developed an MDR P. aeruginosa intraabdominal infection where serious and life‐threatening toxicities to aminoglycosides and polymyxin antibiotics led to the utilization of cefiderocol on compassionate use approval. The isolate was susceptible to cefiderocol, and the patient was treated for 28 days of therapy. He demonstrated clinical and radiographic resolution of his infection and was discharged to home.

AbstractBackgroundPrevention of skin cancer includes early diagnosis and photoprotection, such as by physician‐performed total skin examination (TSE) and patient‐performed self‐skin examination (SSE). Hypothesizing that 90% of our patients receive an annual TSE, photoprotection counseling, and SSE instruction, we assessed the extent to which this was documented in patients' records. We also sought to identify differences in documentation of TSE, photoprotection counseling, and instruction on SSE with or without use of a dictation template prompting documentation.Materials and methodsRetrospective review of a random sample of 400 patients in an outpatient dermatology practice of a tertiary care academic medical center for any dermatology appointment between May 1 and July 31, 2007. Exclusion criteria included refusal to undergo TSE, lack of access to skin (e.g. wheelchair‐bound or in cast), or inappropriate visit type (e.g. for acne, psoriasis, or lupus).ResultsOf 400 randomly selected patients, 313 met inclusion criteria. The dictation template was used in 133; of these, 89% (119/133) had documentation in their clinical note of a TSE (exclusive of the buttocks or groin area), and 98% (130/133) had documentation of instruction on sun protection and SSE. Without use of the dictation template, these percentages dropped to 78% (140/180) and 20% (36/180), respectively. Physicians using a dictation template were more likely to document having conducted a TSE and instructed patients on photoprotection and SSE.ConclusionsA dictation template aids documentation of annual TSE and patient education efforts on photoprotection and SSE.