Adjunctive transferrin to reduce the emergence of antibiotic resistance in Gram-negative bacteria.

BACKGROUND: New strategies are needed to slow the emergence of antibiotic resistance among bacterial pathogens. In particular, society is experiencing a crisis of antibiotic-resistant infections caused by Gram-negative bacterial pathogens and novel therapeutics are desperately needed to combat such diseases. Acquisition of iron from the host is a nearly universal requirement for microbial pathogens-including Gram-negative bacteria-to cause infection. We have previously reported that apo-transferrin (lacking iron) can inhibit the growth of Staphylococcus aureus in culture and diminish emergence of resistance to rifampicin. OBJECTIVES: To define the potential of apo-transferrin to inhibit in vitro growth of Klebsiella pneumoniae and Acinetobacter baumannii, key Gram-negative pathogens, and to reduce emergence of resistance to antibiotics. METHODS: The efficacy of apo-transferrin alone or in combination with meropenem or ciprofloxacin against K. pneumoniae and A. baumannii clinical isolates was tested by MIC assay, time-kill assay and assays for the selection of resistant mutants. RESULTS: We confirmed that apo-transferrin had detectable MICs for all strains tested of both pathogens. Apo-transferrin mediated an additive antimicrobial effect for both antibiotics against multiple strains in time-kill assays. Finally, adding apo-transferrin to ciprofloxacin or meropenem reduced the emergence of resistant mutants during 20 day serial passaging of both species. CONCLUSIONS: These results suggest that apo-transferrin may have promise to suppress the emergence of antibiotic-resistant mutants when treating infections caused by Gram-negative bacteria.

Inverse Probability Weighting Enhances Absolute Risk Estimation in Three Common Study Designs of Nosocomial Infections.

Purpose: When studying nosocomial infections, resource-efficient sampling designs such as nested case-control, case-cohort, and point prevalence studies are preferred. However, standard analyses of these study designs can introduce selection bias, especially when interested in absolute rates and risks. Moreover, nosocomial infection studies are often subject to competing risks. We aim to demonstrate in this tutorial how to address these challenges for all three study designs using simple weighting techniques. Patients and Methods: We discuss the study designs and explain how inverse probability weights (IPW) are applied to obtain unbiased hazard ratios (HR), odds ratios and cumulative incidences. We illustrate these methods in a multi-state framework using a dataset from a nosocomial infections study (n = 2286) in Moscow, Russia. Results: Including IPW in the analysis corrects the unweighted naïve analyses and enables the estimation of absolute risks. Resulting estimates are close to the full cohort estimates using substantially smaller numbers of patients. Conclusion: IPW is a powerful tool to account for the unequal selection of controls in case-cohort, nested case-control and point prevalence studies. Findings can be generalized to the full population and absolute risks can be estimated. When applied to a multi-state model, competing risks are also taken into account.

The incidence and outcomes of healthcare-associated respiratory tract infections in non-ventilated neurocritical care patients: Results of a 10-year cohort study.

The incidence of healthcare-associated respiratory tract infections in non-ventilated patients (NVA-HARTI) in neurosurgical intensive care units (ICUs) is unknown. The impact of NVA-HARTI on patient outcomes and differences between NVA-HARTI and ventilator-associated healthcare-associated respiratory tract infections (VA-HARTI) are poorly understood. Our objectives were to report the incidence, hospital length of stay (LOS), ICU LOS, and mortality in NVA-HARTI patients and compare these characteristics to VA-HARTI in neurocritical care patients. This cohort study was conducted in a neurosurgical ICU in Moscow. From 2011 to 2020, all patients with an ICU LOS > 48 h were included. A competing risk model was used for survival and risk analysis. A total of 3,937 ICU admissions were analyzed. NVA-HARTI vs VA-HARTI results were as follows: cumulative incidence 7.2 (95%CI: 6.4-8.0) vs 15.4 (95%CI: 14.2-16.5) per 100 ICU admissions; incidence rate 4.2 ± 2.0 vs 9.5 ± 3.0 per 1000 patient-days in the ICU; median LOS 32 [Q1Q3: 21, 48.5] vs 46 [Q1Q3: 28, 76.5] days; median ICU LOS 15 [Q1Q3: 10, 28.75] vs 26 [Q1Q3: 17, 43] days; mortality 12.3% (95%CI: 7.9-16.8) vs 16.7% (95%CI: 13.6-19.7). The incidence of VA-HARTI decreased over ten years while NVA-HARTI incidence did not change. VA-HARTI was an independent risk factor of death, OR 1.54 (1.11-2.14), while NVA-HARTI was not. Our findings suggest that NVA-HARTI in neurocritical care patients represents a significant healthcare burden with relatively high incidence and associated poor outcomes. Unlike VA-HARTI, the incidence of NVA-HARTI remained constant despite preventive measures. This suggests that extrapolating VA-HARTI research findings to NVA-HARTI should be avoided.

ERAS for Head and Neck Tissue Transfer Reduces Opioid Usage, Peak Pain Scores, and Blood Utilization.

OBJECTIVES: We implement a novel enhanced recovery after surgery (ERAS) protocol with pre-operative non-opioid loading, total intravenous anesthesia, multimodal peri-operative analgesia, and restricted red blood cell (pRBC) transfusions. 1) Compare differences in mean postoperative peak pain scores, opioid usage, and pRBC transfusions. 2) Examine changes in overall length of stay (LOS), intensive care unit LOS, complications, and 30-day readmissions. METHODS: Retrospective cohort study comparing 132 ERAS vs. 66 non-ERAS patients after HNC tissue transfer reconstruction. Data was collected in a double-blind fashion by two teams. RESULTS: Mean postoperative peak pain scores were lower in the ERAS group up to postoperative day (POD) 2. POD0: 4.6 ± 3.6 vs. 6.5 ± 3.5; P = .004) (POD1: 5.2 ± 3.5 vs. 7.3 ± 2.3; P = .002) (POD2: 4.1 ± 3.5 vs. 6.6 ± 2.8; P = .000). Opioid utilization, converted into morphine milligram equivalents, was decreased in the ERAS group (POD0: 6.0 ± 9.8 vs. 10.3 ± 10.8; P = .010) (POD1: 14.1 ± 22.1 vs. 34.2 ± 23.2; P = .000) (POD2: 11.4 ± 19.7 vs. 37.6 ± 31.7; P = .000) (POD3: 13.7 ± 20.5 vs. 37.9 ± 42.3; P = .000) (POD4: 11.7 ± 17.9 vs. 36.2 ± 39.2; P = .000) (POD5: 10.3 ± 17.9 vs. 35.4 ± 45.6; P = .000). Mean pRBC transfusion rate was lower in ERAS patients (2.1 vs. 3.1 units, P = .017). There were no differences between ERAS and non-ERAS patients in hospital LOS, ICU LOS, complication rates, and 30-day readmissions. CONCLUSION: Our ERAS pathway reduced postoperative pain, opioid usage, and pRBC transfusions after HNC reconstruction. These benefits were obtained without an increase in hospital or ICU LOS, complications, or readmission rates. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E792-E799, 2021.

Healthcare-associated ventriculitis and meningitis in a neuro-ICU: Incidence and risk factors selected by machine learning approach.

PURPOSE: To define the incidence of healthcare-associated ventriculitis and meningitis (HAVM) in the neuro-ICU and to identify HAVM risk factors using tree-based machine learning (ML) algorithms. METHODS: An observational cohort study was conducted in Russia from 2010 to 2017, and included high-risk neuro-ICU patients. We utilized relative risk analysis, regressions, and ML to identify factors associated with HAVM development. RESULTS: 2286 patients of all ages were included, 216 of them had HAVM. The cumulative incidence of HAVM was 9.45% [95% CI 8.25-10.65]. The incidence of EVD-associated HAVM was 17.2 per 1000 EVD-days or 4.3% [95% CI 3.47-5.13] per 100 patients. Combining all three methods, we selected four important factors contributing to HAVM development: EVD, craniotomy, superficial surgical site infections after neurosurgery, and CSF leakage. The ML models performed better than regressions. CONCLUSION: We first reported HAVM incidence in a neuro-ICU in Russia. We showed that tree-based ML is an effective approach to study risk factors because it enables the identification of nonlinear interaction across factors. We suggest that the number of found risk factors and the duration of their presence in patients should be reduced to prevent HAVM.

Implementing an infection control and prevention program decreases the incidence of healthcare-associated infections and antibiotic resistance in a Russian neuro-ICU.

Background: The impact of infection prevention and control (IPC) programs in limited resource countries such as Russia are largely unknown due to a lack of reliable data. The aim of this study is to evaluate the effect of an IPC program with respect to healthcare associated infection (HAI) prevention and to define the incidence of HAIs in a Russian ICU. Methods: A pioneering IPC program was implemented in a neuro-ICU at Burdenko Neurosurgery Institute in 2010 and included hand hygiene, surveillance, contact precautions, patient isolation, and environmental cleaning measures. This prospective observational cohort study lasted from 2011 to 2016, included high-risk ICU patients, and evaluated the dynamics of incidence, etiological spectrum, and resistance profile of four types of HAIs, including subgroup analysis of device-associated infections. Survival analysis compared patients with and without HAIs. Results: We included 2038 high-risk patients. By 2016, HAI cumulative incidence decreased significantly for respiratory HAIs (36.1% vs. 24.5%, p-value = 0.0003), urinary-tract HAIs (29.1% vs. 21.3%, p-value = 0.0006), and healthcare-associated ventriculitis and meningitis (HAVM) (16% vs. 7.8%, p-value = 0.004). The incidence rate of EVD-related HAVM dropped from 22.2 to 13.5 cases per 1000 EVD-days. The proportion of invasive isolates of Klebsiella pneumoniae and Acinetobacter baumannii resistant to carbapenems decreased 1.7 and 2 fold, respectively. HAVM significantly impaired survival and independently increasing the probability of death by 1.43. Conclusions: The implementation of an evidence-based IPC program in a middle-income country (Russia) was highly effective in HAI prevention with meaningful reductions in antibiotic resistance.

Surgical correction of pectus arcuatum.

BACKGROUND: Pectus arcuatum is a rear congenital chest wall deformity and methods of surgical correction are debatable. METHODS: Surgical correction of pectus arcuatum always includes one or more horizontal sternal osteotomies, resection of deformed rib cartilages and finally anterior chest wall stabilization. The study is approved by the institutional ethical committee and has obtained the informed consent from every patient. RESULTS: In this video we show our modification of pectus arcuatum correction with only partial sternal osteotomy and further stabilization by vertical parallel titanium plates. CONCLUSIONS: Reported method is a feasible option for surgical correction of pectus arcuatum.