No abstract

Two patients developed symptoms of neurotoxicity after receiving intravenous polymyxin B for the treatment of MDR gram-negative infections.

Background Immunosuppressive therapies proposed for Coronavirus disease 2019 (COVID-19) management may predispose to secondary infections. We evaluated the association of immunosuppressive therapies with bloodstream-infections (BSIs) in hospitalized COVID-19 patients. Methods This was an institutional review board-approved retrospective, multicenter, cohort study of adults hospitalized with COVID-19 over a 5-month period. We obtained clinical, microbiologic and laboratory data from electronic medical records. Propensity-score-matching helped create balanced exposure groups. Demographic characteristics were compared across outcome groups (BSI/no BSI) using two-sample t-test and Chi-Square test for continuous and categorical variables respectively, while immunosuppressive therapy use was compared using McNemar’s test. Conditional logistic regression helped assess the association between immunosuppressive therapies and BSIs. Results 13,007 patients were originally included, with propensity-score-matching producing a sample of 6,520 patients. 3.74% and 3.97% were diagnosed with clinically significant BSIs in the original and propensity-score-matched populations respectively. COVID-19 patients with BSIs had significantly longer hospitalizations, higher intensive care unit admission and mortality rates compared to those without BSIs. On univariable analysis, combinations of corticosteroids/anakinra [odds-ratio (OR) 2.00, 95% confidence intervals (C.I.) 1.05-3.80, P value.0342] and corticosteroids/tocilizumab [OR 2.13, 95% C.I. 1.16–3.94, P value .0155] were significantly associated with BSIs. On multivariable analysis (adjusting for confounders), combination corticosteroids/tocilizumab were significantly associated with any BSI [OR 1.97, 95% C.I. 1.04–3.73, P value.0386] and with bacterial BSIs [OR 2.13, 95% C.I. 1.12–4.05, p-value 0.0217]. Conclusions Combination immunosuppressive therapies were significantly associated with BSI occurrence in COVID-19 patients; their use warrants increased BSI surveillance. Further studies are needed to establish their causative role.

This study was conducted to determine whether an antimicrobially induced (ASP-250) increase in serum IGF-I was the result of differences in feed intake. Serum IGF-I concentrations were measured in crossbred pigs that were fed a control diet or a diet supplemented with ASP-250 either for ad libitum consumption or limited to 85% of the control pigs' consumption. The pigs that consumed either diet ad libitum, control or ASP-250, consumed similar quantities of feed. The ASP-250 ad libitum-intake pigs had serum IGF-I concentrations that were greater (P<.01) than those of their ad libitum-intake control littermates. Similarly, the ASP-250 limit-fed pigs had serum IGF-I concentrations that were greater (P<.01) than those of the controls. Although the serum IGF-I concentrations of pigs fed the ASP-250-supplemented diet for ad libitum intake were greater than the serum IGF-I concentrations of the pigs limit-fed the ASP-250-supplemented diet, the differences were not significant (P<.08). The ASP-250-fed pigs had higher serum IGF binding protein (BP)-3 concentrations than did their control littermates (P<.003). A time course of antimicrobially induced alterations in serum IGF-I concentrations revealed that the effect of increased serum IGF-I levels in ASP-250-supplemented pigs (P<.02) was observed within 4 d and was maintained throughout the 4-wk study. These findings show that feed intake is not responsible for the increase in serum IGF-I observed with ASP-250 supplementation. Additionally, the antimicrobially induced increase in serum IGF-I concentrations occurs within a few days after initiation of the treatment.

Background: Polymyxin B’s package insert recommends renal adjustment. Contemporary studies suggest it does not require renal adjustment. Objective: To determine whether time to acute kidney injury (AKI) differs between renally adjusted and nonadjusted intravenous (IV) polymyxin B. Methods: This retrospective chart review compared time to AKI after renally adjusted and nonadjusted IV polymyxin B administration. It included patients who were 18 years or older, received IV polymyxin B, and had creatinine clearance below 80 mL/min, and excluded ones who had AKI, received renal replacement therapy, or were pregnant. Results: Fifty-four patients were included. There was not any statistical association between dosing type and time to AKI ( P = .13). Incidence of nephrotoxicity, mortality, and length of stay (LOS) were higher in the renally adjusted arm (21.7% vs 6.5%, 17.4% vs 6.5%, and 16 vs 14 days, respectively). Four patients received concomitant ascorbic acid; not one developed AKI. Conclusion: A significant association between IV polymyxin B dosing type and time to AKI was not found. Adverse events were higher in the renally adjusted arm. This suggests that nonadjusted IV polymyxin B may be preferred in patients with renal impairment. Ascorbic acid may mitigate IV polymyxin B's nephrotoxic potential. Further studies are needed to corroborate these findings.