Sara Alosaimy

Acinetobacter baumannii , particularly when carbapenem resistant (CRAB), is one of the most challenging pathogens in the health care setting. This is complicated by the fact that there is no consensus guideline regarding management of A. baumannii infections.

Vancomycin (VAN)-associated acute kidney injury (AKI) is increased when VAN is combined with certain beta-lactams (BLs) such as piperacillin-tazobactam (TZP) but has not been evaluated with ceftolozane-tazobactam (C/T). Our aim was to investigate the AKI incidence of VAN in combination with C/T (VAN/C/T) compared with VAN in combination to TZP (VAN-TZP). We conducted a multicenter, observational, comparative study across the United States. The primary analysis was a composite outcome of AKI and risk, injury, failure, loss, end stage renal disease; Acute Kidney Injury Network; or VAN-induced nephrotoxicity according to the consensus guidelines. Multivariable logistic regression analysis was conducted to adjust for confounding variables and stratified Kaplan–Meir analysis to assess the time to nephrotoxicity between the 2 groups. We included VAN/C/T (n = 90) and VAN-TZP (n = 284) at an enrollment ratio of 3:1. The primary outcome occurred in 12.2% vs 25.0% in the VAN-C/T and VAN-TZP groups, respectively (P = .011). After adjusting for confounding variables, VAN-TZP was associated with increased odds of AKI compared with VAN-C/T; with an adjusted odds ratio of 3.308 (95% confidence interval, 1.560–6.993). Results of the stratified Kaplan–Meir analysis with log-rank time-to-nephrotoxicity analysis indicate that time to AKI was significantly shorter among patients who received VAN-TZP (P = .004). Cox proportional hazards analysis demonstrated that TZP was consistent with the primary analysis (P = .001). Collectively, our results suggest that the AKI is not likely to be related to tazobactam but rather to piperacillin, which is a component in VAN-TZP but not in VAN-C/T.

A multicenter case series of 21 patients were treated with imipenem-cilastatin-relebactam. There were mixed infection sources, with pulmonary infections (11/21,52%) composing the majority. The primary pathogen was Pseudomonas aeruginosa (16/21, 76%), and 15/16 (94%) isolates were multidrug-resistant. Thirty-day survival occurred in 14/21 (67%) patients. Two patients experienced adverse effects.

People who inject drugs (PWID) are at high risk for infective endocarditis (IE) with high-mortality pathogens such as methicillin-resistant Staphylococcus aureus (MRSA). Stigma against PWID may cause differences in treatment and outcomes between these patients infected with MRSA IE. Single center retrospective cohort study from August 2006 to February 2021 that includes adult patients diagnosed with IE. Primary outcomes included 90-day all-cause mortality, 60-day MRSA recurrence, 60-day readmission, and hospital length of stay (LOS). Statistical analysis was performed by chi-square, t-test, and Mann-Whitney-U as appropriate. A total of 214 patients were diagnosed with MRSA IE; 89 PWID and 125 non-PWID. The mean (SD) age was 47.4±12.4 years (PWID) vs 59.3 ±16.0 years (non-PWID) (p< 0.001). Patients were primarily male (56%), but differed in terms of race 34% African-American (AA) (PWID) vs 66% AA (non-PWID) (p< 0001). Mean APACHE II scores differed between groups: 16(±9.9) (PWID) vs 19(±8.1) (non-PWID) (p< 0.008). Among patients who cleared bacteremia, mean (SD) duration was 5.7(±3.9) days and was not significant between groups (p< 0.64). Valve-type was 93% native and 7% prosthetic and not different between groups (p< 0.16). Infectious Diseases consult did not differ at 96% overall (p< 0.31), but pursuit of source control nearly reached significance at 27% for PWID vs 41% non-PWID (p< 0.06). Similarly, use of combination therapy daptomycin and ceftaroline was nearly significant: 21% (PWID) vs 12% (non-PWID) (p< 0.09). Odds ratio of PWID and combination therapy remained non-significant after regression: 0.39(0.14-1.1,p< 0.07). Primary 90-day mortality was lower in PWID vs non-PWID (15% vs 30%) respectively (p< 0.01), but did not differ in 60-day MRSA recurrence (p< 1.0) at 9%, 60-day readmission (p< 1.0) at 33%, or median LOS (IQR) (p< 0.46) at 15 (10-24) days overall. While PWID are significantly younger, less critically ill, and have lower mortality compared to non-PWID, they have similar LOS, MRSA recurrence, and readmission rates. Analyses suggest a potential difference in the pursuit of source control and combination therapy among PWID, however more studies may be needed to achieve significance. Michael J. Rybak, PharmD, MPH, PhD, Paratek Pharmaceuticals (Research Grant or Support)

Methicillin-resistant Staphylococcus aureus (MRSA) is associated with substantial morbidity and mortality. Vancomycin (VAN) has been used as the gold standard treatment for invasive MRSA infections for decades but, unfortunately, the reliance of VAN as the primary treatment option against these infections has led to a reduction in VAN susceptibility in MRSA isolates. Although daptomycin (DAP) is another common treatment option against invasive MRSA infections, it has been shown that the development of VAN resistance can lead to DAP nonsusceptibility. VAN or DAP backbone regimens in combination with other antibiotics has been advocated as an alternative approach to improve patient outcomes in VAN/DAP-susceptible infections, enhance outcomes in infections caused by isolates with reduced VAN/DAP susceptibility, and/or prevent the emergence of VAN/DAP resistance or further resistance. A peer-reviewed literature search was conducted using Medline, Google Scholar and PubMed databases. The primary purpose of this review is to describe the mechanisms and epidemiology of MRSA isolates with a reduction in VAN and/or DAP susceptibility, evaluate in vitro and in vivo literature describing combination therapy (CT) against MRSA isolates with reduced VAN and/or DAP susceptibility and describe studies involving the clinical outcomes of patients treated with CT against invasive MRSA infections.

Older adults have a seven times greater risk than younger adults of being hospitalized due to an adverse drug event.