Impact of coronavirus disease 2019 (COVID-19) on antimicrobial resistance among major pathogens causing healthcare-associated infection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused great impact on healthcare systems, including antibiotic usage and multi-drug resistant (MDR) bacterial infections at hospitals. We aim to investigate the trends of antimicrobial resistance among the major pathogens causing healthcare-associated infection (HAI) at intensive care units (ICU). MATERIAL AND METHODS: The demographic characteristics of hospitalization, usage of antimicrobial agents, counted by half-an-year DID (defined daily dose per 1000 patient-days), and HAI density of five major MDR bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumoniae (CRKP), and carbapenem-resistant Pseudomonas aeruginosa (CRPA), of ICU patients at a medical center in Taiwan during January 2017 to December 2021 were collected and analyzed. RESULTS: The total antibiotic usage, counted by DID, had a significant increasing trend, before COVID-19 occurrence in 2017-2019, but no further increase during the pandemic period in 2020-2021. However, comparing the two time periods, antibiotics consumption was significantly increased during pandemic period. There was no significant change of HAI density in MRSA, VRE, CRAB, CRKP, and CRPA, comparing the pandemic to the pre-pandemic period. Although, CRKP and CRPA infection rates were increasing during the pre-pandemic period, there was no further increase of CRKP and CRPA HAI rates during the pandemic period. CONCLUSION: During COVID-19 pandemic, there was no significant increase in HAI density of five major MDR bacteria at ICU in Taiwan, despite increased antibiotic usage. Strict infection prevention measures for COVID-19 precautions and sustained antimicrobial stewardship probably bring these effects.

Evaluation of the Negative Predictive Value of Methicillin-Resistant Staphylococcus aureus Nasal Swab Screening in the Medical Intensive Care Units and Its Effect on Antibiotic Duration.

Background: In addition to active surveillance of methicillin-resistant Staphylococcus aureus (MRSA) carrier, MRSA nasal screening can be valuable for antibiotic de-escalation. This study aimed to assess the correlations between the MRSA nasal swab and subsequent culture results in patients admitted to medical intensive care units (MICU). The impact of MRSA nasal swab on the antibiotic duration was also evaluated. Materials and Methods: This retrospective study enrolled patients who received glycopeptides in the MICU of a medical center in 2019. Patients treated with glycopeptides for over 2 days before MICU admission were excluded. The associated data were collected through the electronic medical record system. The negative predictive value (NPV) of MRSA nasal swabs for MRSA infection was calculated, and their influence on empirical glycopeptide treatment duration was analyzed. Results: Of the 338 patients who met the inclusion criteria, 277 underwent MRSA nasal screening. The NPV of MRSA-negative nasal swab for subsequent MRSA infection was 98.4%. The glycopeptide treatment duration of the patients with and without nasal screening was not significantly different (4.2 ± 2.8 vs 4.4 ± 3.0 days, p = 0.577). Of the 120 patients with MRSA-negative nasal swab and no subsequent MRSA infection, 75 continued empirical glycopeptides therapy. The additional treatment time was 3 days (interquartile range: 2-6 days). Conclusion: The MRSA nasal swabs have high NPV for MRSA infection in critically ill patients. However, it has no impact on the empirical glycopeptide treatment duration. The value of MRSA nasal swabs should be advocated to optimize antibiotic therapy.

Comparison of risk of acute kidney injury between patients receiving the combination of teicoplanin and piperacillin/tazobactam versus vancomycin and piperacillin/tazobactam.

BACKGROUND/PURPOSE: To compare the risk of acute kidney injury (AKI) among patients receiving teicoplanin (TA) plus piperacillin/tazobactam (TZP) versus vancomycin (VAN) plus TZP. METHODS: This was a retrospective cohort study using electronic health records. Patients were included if a combination of glycopeptide and TZP or other selected ß-lactams were used during hospitalization. In the main analysis, two study groups were identified: TA + TZP and VAN + TZP. We used 1:1 propensity score matching to control for potential confounders, and hazard ratio (HR) of AKI between study groups was calculated. We further compared the risk of AKI between patients receiving VAN + TZP and VAN + ß-lactams as an auxiliary analysis to verify the validity of the study design. RESULTS: The final sample contained 211 pairs of patients receiving either TA + TZP or VAN + TZP. The median dosage of TA and VAN were 10.3 and 26.7 mg/kg/day, respectively. The median trough level of VAN was 12.3 mg/L. The AKI risk in the TA + TZP group was similar to that in the VAN + TZP group (12.3% vs. 11.4%; HR = 1.25 [0.72-2.18], p = 0.44). The auxiliary analysis showed a higher risk of AKI in the VAN + TZP group than in the VAN + ß-lactam group (13.2% vs. 9.6%; HR = 1.63 [1.04-2.55], p = 0.03). CONCLUSION: Our study results showed that the risk of AKI were similar for patients receiving TA + TZP and VAN + TZP. However, low VAN and high TA dose may play a role in this finding. Further investigation on the association between AKI and TA + TZP is required.

Nephrotoxicity of teicoplanin-based combination therapy: focus on piperacillin/tazobactam and other anti-pseudomonal ß-lactams.

BACKGROUND: The concurrent use of vancomycin and piperacillin/tazobactam increases the risk of acute kidney injury (AKI) compared with vancomycin use with other anti-pseudomonal ß-lactams (OAPBs). Teicoplanin is a glycopeptide antibiotic with lower nephrotoxicity than that of vancomycin. Whether the concomitant use of teicoplanin and piperacillin/tazobactam also increases the risk of AKI remains unknown. OBJECTIVES: To evaluate the AKI risk between teicoplanin-piperacillin/tazobactam and teicoplanin-OAPBs. METHODS: This was a retrospective, propensity score-matched cohort study. Adult patients receiving teicoplanin-based combination therapy were included. OAPBs included cefepime, cefoperazone/sulbactam, ceftazidime, doripenem, imipenem/cilastatin and meropenem. Propensity score matching was performed to balance demographic and confounding factors. The primary endpoint was AKI during combination therapy. RESULTS: After propensity score matching, 954 patients (teicoplanin-piperacillin/tazobactam: teicoplanin-OAPBs, 1:3 matched, 243 pairs in total) were included for analysis. The mean age was 66.3 years in the matched cohort and 17.1% of patients had shock. Use of nephrotoxic medications (45.7% versus 48.7%) and baseline renal function (78.88 ± 31.26 versus 81.05 ± 31.53 mL/min/1.73 m2) were similar in the two groups. The median teicoplanin dose was 10.7 mg/kg in both groups. The groups did not differ significantly in terms of AKI risk (14.8% versus 14.2%, P = 0.815). However, the time to AKI appeared shorter in the teicoplanin-piperacillin/tazobactam group (4.64 ± 2.33 versus 6.29 ± 4.72 days, P = 0.039). CONCLUSIONS: The combination of teicoplanin and piperacillin/tazobactam was not associated with an increased risk of AKI compared with teicoplanin and OAPBs.

Augmented renal clearance is associated with inadequate antibiotic pharmacokinetic/pharmacodynamic target in Asian ICU population: a prospective observational study.

BACKGROUND: Augmented renal clearance (ARC) is common in critically ill patients and could result in subtherapeutic antibiotic concentration. However, data in the Asian population are still lacking. The aim of this study was to explore the incidence and risk factors of ARC and its effect on ß-lactam pharmacokinetics/pharmacodynamics (PK/PD) in Asian populations admitted to a medical ICU. In addition, we evaluated the appropriateness of using three estimated glomerular filtration (eGFR) formulas [Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)] as screening tools. METHODS: We measured 2-, 8-, and 24-hr creatinine clearance (CLCr) and calculated eGFR by using three formulas for each. ARC was defined as CLCr24hr >130 mL/min/1.73 m2. Concentrations at the mid-dosing interval and prior to the next dose were collected if patients received the ß-lactam antibiotic of piperacillin/tazobactam, cefepime, and meropenem, to determine the PK/PD index of fT > MIC. Multiple logistic regression analysis was conducted to identify the risk factors for ARC. Pearson correlation coefficient and the Bland and Altman method were applied to assess the accuracy of CLCr2hr, CLCr8hr, and eGFR for predicting ARC. RESULTS: Of 100 patients, 46 (46%) manifested ARC. Younger age (<50 years) and lower Sequential Organ Failure Assessment score increased the likelihood of ARC. ARC resulted in a low chance of achieving 50% fT >4MIC (33% vs 75%, p<0.01), 100% fT > MIC (23% vs 69%, p<0.01), and 100% fT >4MIC (3% vs 25%, p<0.02). CLCr8hr wielded the best correlation and agreement with CLCr24hr. eGFRCG was the most appropriate screening tool, and the optimal cutoff value for detecting ARC was 130.5 mL/min/1.73 m2. CONCLUSION: ARC is associated with inadequate ß-lactam PK/PD target in Asian ICU.

Safety of high-dose daptomycin in patients with severe renal impairment.

BACKGROUND: Treatment options are limited for infections due to multidrug-resistant Gram-positive pathogens. Daptomycin is a lipopeptide antibiotic with concentration-dependent killing characteristic and dose-dependent post-antibiotic effect. To achieve optimized pharma-codynamic effect, some experts advocated using a high dose of daptomycin (≥9 mg/kg) for severe infections. However, the safety of high-dose therapy in patients with renal impairment remains unknown. This study was aimed to evaluate the safety of daptomycin in patients with severe renal impairment. METHODS: This was a retrospective study performed by reviewing electronic medical records. Patients with severe renal impairment who were treated with daptomycin in a tertiary teaching hospital between January 1, 2013, and June 30, 2016, were included for evaluation. The incidence rates of creatine kinase (CK) elevation between high-dose (≥9 mg/kg) and standard-dose (<9 mg/kg) groups were compared. RESULTS: Overall, 164 patients met the inclusion criteria, and 114 (69.5%) of them were on renal replacement therapy. Vancomycin-resistant enterococci were the most common pathogens (61.3%) of the patients with documented pathogens. The treatment success rate was 51.6% in the 91 patients with bacteremia. The average dose of daptomycin was 8.0±2.3 mg/kg, and 37 (22.6%) patients received ≥9 mg/kg. CK levels were followed in 108 (65.9%) patients. Significantly higher incidence of CK elevation was found in the high-dose group compared with that in the standard-dose group (10.8% vs 1.6%, P<0.05). Moreover, patients with elevated CK received a higher dose of daptomycin than those without (9.3±1.2 vs 7.9±2.3 mg/kg, P<0.05). There was no significant difference in the rate of CK elevation between patients treated with different dosing frequency or with the concurrent use of statins, fibrate, or colchicine. CONCLUSIONS: In patients with severe renal impairment, high-dose (≥9 mg/kg) daptomycin therapy may result in a significantly higher incidence of CK elevation. More frequent CK monitoring is warranted to avoid potential harm in this population.