Cost-effectiveness of linezolid to ventilator-associated pneumonia in Colombia.

INTRODUCTION: Ventilator-associated pneumonia (VAP) is a prominent cause of morbidity and mortality in intensive care unit (ICU) patients. Due to the increase in Methicillin resistant Staphylococcus aureus infection, it is important to consider other more effective and safer alternatives compared to vancomycin. This motivates evaluating whether the use of an apparently more expensive drug such as linezolid can be cost-effective in Colombia. METHODS: A decision tree was used to simulate the results in terms of the cost and proportion of cured patients. In the simulation, patients can receive antibiotic treatment with linezolid (LZD 600 mg IV/12 h) or vancomycin (VCM 15 mg/kg iv/12 h) for 7 days, patients they can experience events adverse (renal failure and thrombocytopenia). The model was analyzed probabilistically, and a value of information analysis was conducted to inform the value of conducting further research to reduce current uncertainties in the evidence base. Cost-effectiveness was evaluated at a willingness-to-pay (WTP) value of US$5180. RESULTS: The mean incremental cost of LZD versus VCM is US$-517. This suggests that LZD is less costly. The proportion of patients cured when treated with LZD compared with VCM is 53 vs. 43%, respectively. The mean incremental benefit of LZD versus VCM is 10 This position of absolute dominance (LZD has lower costs and higher proportion of clinical cure than no supplementation) is unnecessary to estimate the incremental cost-effectiveness ratio. There is uncertainty with a 0.999 probability that LZD is more cost-effective than VCM. Our base-case results were robust to variations in all assumptions and parameters. CONCLUSION: LNZ is a cost-effective strategy for patients, ≥ 18 years of age, with VAP in Colombia- Our study provides evidence that can be used by decision-makers to improve clinical practice guidelines.

RISK FACTORS OF IN-HOSPITAL INFECTIONS OCCURRENCE IN HEALTHCARE INSTITUTIONS IN UKRAINE AND EU COUNTRIES.

The rapid development of modern scientific medicine and practice (development of genetic engineering, coronary angiography, use of microprocessors (microminiature implant in eye retina, 3D-print of implants, prostheses) is connected with the scientific-technical progress in recent years, which gave impetus to introduction of extremely complex treatment and diagnostic methods. The use of high-tech medical equipment requires the implementation of modern sanitary and anti-epidemic measures of disinfection and sterilization after each manipulation to prevent in-hospital infection/infectious diseases which are related to the grant of medicare (IHI/IPNMD). Every year in the USA, up to 2 million patients who received medical services are registered with IHI/IPNMD cases. IHI/IPNMD is the cause of increased mortality, disability, lengthens stay period of patients in hospitals, increases the financial burden on both patients and healthcare system. According to WHO data mortality from IHI/IPNMD among adult patients ranges from 18.5% to 29.6% and in countries with low- and middle-income level fluctuate in the range of 8.8%-88.9%. Thus, the vital issue today is to strengthen the control system over IHI/IPNMD at all stages of its spread, namely: early detection of sick persons and carriers among patients and medical personnel, monitoring resistance to antibiotics and control over their use in patients treatment, expanding the range of scientific research in the development of new groups of antibacterial drugs, compliance with the sanitary-epidemic regime in hospitals, including the elaboration of modern disinfectants and sterilization agents.

Assessment of the pneumonia severity score in community-acquired and nursing and healthcare-associated pneumonia due to COVID-19.

INTRODUCTION: The Japanese Respiratory Society (JRS) pneumonia guidelines recommend simple predictive rules, the A-DROP scoring system, for assessment of the severity of community-acquired pneumonia (CAP) and nursing and healthcare-associated pneumonia (NHCAP). We evaluated whether the A-DROP system can be adapted for assessment of the severity of coronavirus disease 2019 (COVID-19) pneumonia. METHODS: Data from 1141 patients with COVID-19 pneumonia were analyzed, comprising 502 patients observed in the 1st to 3rd wave period, 338 patients in the 4th wave and 301 patients in the 5th wave in Japan. RESULTS: The mortality rate and mechanical ventilation rate were 0% and 1.4% in patients classified with mild disease (A-DROP score, 0 point), 3.2% and 46.7% in those with moderate disease (1 or 2 points), 20.8% and 78.3% with severe disease (3 points), and 55.0% and 100% with extremely severe disease (4 or 5 points), indicating an increase in the mortality and mechanical ventilation rates in accordance with severity (Cochran-Armitage trend test; p = <0.001). This significant relationship between the severity in the A-DROP scoring system and either the mortality rate or mechanical ventilation rate was observed in patients with COVID-19 CAP and NHCAP. In each of the five COVID-19 waves, the same significant relationship was observed. CONCLUSIONS: The mortality rate and mechanical ventilation rate in patients with COVID-19 pneumonia increased depending on severity classified according to the A-DROP scoring system. Our results suggest that the A-DROP scoring system can be adapted for the assessment of severity of COVID-19 CAP and NHCAP.

The direct medical economic burden of healthcare-associated infections and antimicrobial resistance: A preliminary study in a teaching hospital of Nepal.

OBJECTIVES: Healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) have posed major challenges to South Asia. The purpose of this study is to explore the direct medical economic burden attributable to HAIs and AMR in Nepal. METHODS: A prospective study was conducted in a teaching hospital of Nepal from 16 December 2017 to 16 April 2018. The demographic, clinical, and financial expense data were extracted from medical records, laboratory reports, and hospital information system. STATA 12.0 was used to conduct descriptive analysis, χ2 test, t test, and propensity score matching. RESULTS: The prevalence of HAIs was 3.31% in the hospital. The additional total medical expenses, medicine expenses, out-of-pocket expenses, and hospitalisation days per inpatient attributable to HAIs were $164.63, $114.96, $150.79, and 7 days, respectively. In contrast, the additional direct medical economic burden attributable to HAIs-AMR were US$ 381.15, US$ 202.37, US$ 370.56, and 9 days for each of the counterpart variables. The percentage of out-of-pocket expenses to total medical expenses was 94.24% among the HAIs inpatients, and the percentage was 96.75% among the HAIs-AMR inpatients. CONCLUSIONS: The prevalence of HAIs in the hospital was low, which might be underestimated in a resource-constrained setting. Therefore, this study can only be considered a preliminary one. Moreover, the additional direct medical economic burden was extraordinarily high among the HAIs and the HAIs-AMR inpatients, and most of the expenses were borne by themselves. A systemic solution for sustainable governance is required.

Cost of antibiotics in medical intensive care.

BACKGROUND: Intensive care units are a prime target for monitoring antibiotic consumption and conducting pharmacoeconomic studies because of their considerable antibiotic use. AIM: To evaluate the consumption and cost of antibiotics globally, per family, and for nosocomial and multidrug-resistant infections. METHODS: This is a monocentric, retrospective, and observational study spanning one year (January 1st, 2018, to December 31st, 2018), and covering all patients hospitalized in the medical intensive care unit of Ibn Rochd University Hospital of Casablanca in Morocco. FINDINGS: The global annual consumption of antibiotics accounted for 1410.21 defined daily doses (DDD) per 1000 bed-days from which ß-lactams were the most consumed (768.95 DDD per 1000 bed-days). Community-acquired infections resulted in annual antibiotic consumption of 1340.82 vs 2483.69 g DDD for nosocomial infections. Multidrug-resistant infections resulted in annual consumption of 737.5 g DDD (52.2%). The global cost of prescribed antibiotics amounted to US$118,224.32. The consumption of ß-lactams (38%) and fluoroquinolones (21%) combined cost ∼60% of the total budget. The cost spent on antibiotics for the treatment of nosocomial infections was US$57,544.11 vs 60,859.41 for the treatment of community-acquired infections. The cost of antibiotics prescribed for the treatment of multidrug-resistant infections reached US$47,744.14. CONCLUSION: This study made it possible to identify several aspects of misuse and overconsumption which allowed estimating certain expenses that could be entirely avoidable. As a result, this evaluation would be the first step towards the rationalization of antibiotic use.

A dosing nomograph for cerebrospinal fluid penetration of meropenem applied by continuous infusion in patients with nosocomial ventriculitis.

OBJECTIVES: In difficult-to-treat infections such as nosocomial ventriculitis, meropenem exposure in the infected compartment is often uncertain but crucial for antibacterial effects. The aim of this study was to investigate the cerebrospinal fluid (CSF) penetration of meropenem in patients with nosocomial ventriculitis and to derive a nomograph to predict effective meropenem doses as a function of clinical parameters. METHODS: Retrospective patient data including meropenem serum and CSF levels as well as CSF inflammation markers were analyzed using NONMEM to assess the general pharmacokinetics and CSF penetration. Monte Carlo simulations were used to evaluate different meropenem dosing regimens. Probability of target attainment (PTA) in CSF was assessed, and a nomograph to achieve a target twice the minimal inhibitory concentration (MIC) during the dosing interval (100 %fT > 2x MIC) was developed. RESULTS: A one-compartment model with meropenem clearance dependent on the estimated glomerular filtration rate (CKD-EPI eGFR, p < 0.001) best described meropenem serum pharmacokinetics of 51 critically ill patients. CSF penetration ratio was correlated with the amount of protein in CSF (p < 0.001), with higher CSF protein levels accounting for higher penetration ratios. Preserved renal function (CKD-EPI eGFR >50 mL/min/1.73 m2) and low CSF protein levels (<500 mg/L) resulted in 80% PTA 100 %fT >2xMIC) for a meropenem dose of 6 g/24 h. DISCUSSION: High interindividual variability in meropenem CSF concentration was observed in patients with nosocomial ventriculitis. A nomograph to predict the daily meropenem dose required for target attainment for a given eGFR and CSF protein count was developed.

Burden of illness in carbapenem-resistant Acinetobacter baumannii infections in US hospitals between 2014 and 2019.

BACKGROUND: Carbapenem-resistant (CR) Acinetobacter baumannii is a concerning pathogen in the USA and worldwide. METHODS: To assess the comparative burden of CR vs carbapenem-susceptible (CS) A. baumannii, this retrospective cohort study analyzed data from adult patients in 250 US hospitals from the Premier HealthCare Database (2014-2019). The outcomes analyzed included hospital length of stay (LOS), intensive care unit (ICU) utilization, discharge status, in-hospital mortality, readmission rates and hospital charges. Logistic regression was used for univariate and multivariable assessment of the independent relationship between relevant covariates, with a focus on CR status, and in-hospital mortality. RESULTS: 2047 Patients with CR and 3476 patients with CS A. baumannii infections were included. CR A. baumannii was more commonly isolated in respiratory tract infections (CR 40.7% and CS 27.0%, P < 0.01), whereas CS A. baumannii was more frequently associated with bloodstream infections (CS 16.7% and CR 8.6%, P < 0.01). Patients with CR A. baumannii infections had higher in-hospital (CR 16.4% vs CS 10.0%; P < 0.01) and 30-day (CR 32.2% vs CS 21.6%; P < 0.01) mortality compared to those with CS infections. After adjusting for age, sex, admission source, infection site, comorbidities, and treatment with in vitro active antibiotics within 72 h, carbapenem resistance was independently associated with increased mortality (adjusted odds ratio 1.42 [95% confidence interval 1.15; 1.75], P < 0.01). CR infections were also associated with increases in hospital length of stay (CR 11 days vs CS 9 days; P < 0.01), rate of intensive care unit utilization (CR 62.3% vs CS 45.1%; P < 0.01), rate of readmission with A. baumannii infections (CR 17.8% vs CS 4.0%; P < 0.01) and hospital charges. CONCLUSIONS: These data suggest that the burden of illness is significantly greater for patients with CR A. baumannii infections and are at higher risk of mortality compared with CS infections in US hospitals.

A retrospective study on risk factors and disease burden for hospital-acquired pneumonia caused by multi-drug-resistant bacteria in patients with intracranial cerebral hemorrhage.

PURPOSE: Hospital-acquired pneumonia (HAP) is becoming a serious problem in China, especially caused by multi-drug resistant (MDR), which is a risk factor for poor prognosis of intracranial cerebral hemorrhage (ICH). We investigate the risk factors for HAP among patients with ICH and study the antibiotic use and medical costs of MDR infection. METHODS: We performed a retrospective, case-control, parallel study in Xiangya Hospital. Patients included in this study and diagnosed with basal ganglia hemorrhage were admitted between January 2017 and December 2019. RESULTS: Univariate analysis discovered some personal risk factors including gender (p = .002), age (p = .023), and underlying conditions such as diabetes (p = .036), coronary heart disease (p = .009), and renal insufficiency (p = .001). Invasive medical operations including endotracheal intubation, tracheotomy, ventilator use, lumbar puncture, urinary catheter insertion, and peripherally inserted central catheter (PICC) (p < .001 all) were also risk factors for HAP. Binary logistics regression indicated hospital duration, antibiotic exposure, and urinary catheter insertion explained 91.4% of the variance on HAP (p < 0.01). As for the antibiotic treatment, there were no difference in the duration of use days and total dose per patient between MDR and non-MDR group, except for Tigecycline. Antibiotic costs for the MDR group were significantly higher than those for the non-MDR group and no infection group (p < 0.001). CONCLUSION: To better prevent HAP particularly caused by MDR bacteria, we emphasize the aseptic technique especially in the management of equipment in patient care.

Cost-effectiveness of carbapenem-resistant Enterobacteriaceae (CRE) surveillance in Maryland.

OBJECTIVE: We analyzed the efficacy, cost, and cost-effectiveness of predictive decision-support systems based on surveillance interventions to reduce the spread of carbapenem-resistant Enterobacteriaceae (CRE). DESIGN: We developed a computational model that included patient movement between acute-care hospitals (ACHs), long-term care facilities (LTCFs), and communities to simulate the transmission and epidemiology of CRE. A comparative cost-effectiveness analysis was conducted on several surveillance strategies to detect asymptomatic CRE colonization, which included screening in ICUs at select or all hospitals, a statewide registry, or a combination of hospital screening and a statewide registry. SETTING: We investigated 51 ACHs, 222 LTCFs, and skilled nursing facilities, and 464 ZIP codes in the state of Maryland. PATIENTS OR PARTICIPANTS: The model was informed using 2013-2016 patient-mix data from the Maryland Health Services Cost Review Commission. This model included all patients that were admitted to an ACH. RESULTS: On average, the implementation of a statewide CRE registry reduced annual CRE infections by 6.3% (18.8 cases). Policies of screening in select or all ICUs without a statewide registry had no significant impact on the incidence of CRE infections. Predictive algorithms, which identified any high-risk patient, reduced colonization incidence by an average of 1.2% (3.7 cases) without a registry and 7.0% (20.9 cases) with a registry. Implementation of the registry was estimated to save $572,000 statewide in averted infections per year. CONCLUSIONS: Although hospital-level surveillance provided minimal reductions in CRE infections, regional coordination with a statewide registry of CRE patients reduced infections and was cost-effective.

Mortality, Length of Stay, and Healthcare Costs Associated With Multidrug-Resistant Bacterial Infections Among Elderly Hospitalized Patients in the United States.

BACKGROUND: This study reports estimates of the healthcare costs, length of stay, and mortality associated with infections due to multidrug-resistant bacteria among elderly individuals in the United States. METHODS: We conducted a retrospective cohort analysis of patients aged ≥65 admitted for inpatient stays in the Department of Veterans Affairs healthcare system between 1/2007-12/2018. We identified those with positive cultures for multidrug-resistant bacteria and matched each infected patient to ≤10 control patients. We then performed multivariable regression models to estimate the attributable cost and mortality due to the infection. We also constructed multistate models to estimate the attributable length of stay due to the infection. Finally, we multiplied these pathogen-specific attributable cost, length of stay, and mortality estimates by national case counts from hospitalized patients in 2017. RESULTS: Our cohort consisted of 87 509 patients with infections and 835 048 matched controls. Costs were higher for hospital-onset invasive infections, with attributable costs ranging from $22 293 (95% confidence interval: $19 101-$24 485) for methicillin-resistant Staphylococcus aureus (MRSA) to $57 390 ($34 070-$80 710) for carbapenem-resistant (CR) Acinetobacter. Similarly, for hospital-onset invasive infections, attributable mortality estimates ranged from 14.2% (12.2-16.2%) for MRSA to 24.1% (12.1-36.0%) for CR Acinetobacter. The aggregate cost of these infections was an estimated $1.9 billion ($1.3 billion-$2.5 billion) with 11 852 (8719-14 985) deaths and 448 224 (354 513-541 934) inpatient days in 2017. CONCLUSIONS: Efforts to prevent these infections due to multidrug-resistant bacteria could save a significant number of lives and healthcare resources.

The 2018 Global Point Prevalence Survey of antimicrobial consumption and resistance in 47 Canadian hospitals: a cross-sectional survey.

BACKGROUND: Patient-level surveillance of antimicrobial use (AMU) in Canadian hospitals empowers the reduction of inappropriate AMU and was piloted in 2017 among 14 hospitals in Canada. We aimed to describe AMU on the basis of patient-level data in Canadian hospitals in 2018 in terms of antimicrobial prescribing prevalence and proportions, antimicrobial indications, and agent selection in medical, surgical and intensive care wards. METHODS: Canadian adult, pediatric and neonatal hospitals were invited to participate in the standardized web-based cross-sectional Global Point Prevalence Survey of Antimicrobial Consumption and Resistance (Global-PPS) conducted in 2018. An identified site administrator assigned all wards admitting inpatients to specific surveyors. A physician, pharmacist or nurse with infectious disease training performed the survey. The primary outcomes were point prevalence rates for AMU over the study period regarding prescriptions, indications and agent selection in medical, surgical and intensive care wards. The secondary outcomes were AMU for resistant organisms and practice appropriateness evaluated on the basis of quality indicators. Antimicrobial consumption is presented in terms of prevalence and proportions. RESULTS: Forty-seven of 118 (39.8%) hospitals participated in the survey; 9 hospitals were primary care centres, 15 were secondary care centres and 23 were tertiary or specialized care centres. Of 13 272 patients included, 33.5% (n = 4447) received a total of 6525 antimicrobials. Overall, 74.1% (4832/6525) of antimicrobials were for therapeutic use, 12.6% (n = 825) were for medical prophylaxis, 8.9% (n = 578) were for surgical prophylaxis, 2.2% (n = 143) were for other use and 2.3% (n = 147) were for unidentified reasons. A diagnosis or indication was documented in the patient's file at the initiation for 87.3% (n = 5699) of antimicrobials; 62.9% (n = 4106) of antimicrobials had a stop or review date; and 72.0% (n = 4697) of prescriptions were guided by local guidelines. INTERPRETATION: Overall, three-quarters of AMU was for therapeutic use across participating hospitals. Canadian hospitals should be further incentivized to create and adapt local guidelines on the basis of recent antimicrobial resistance data.

The Epidemiology and Pathogenesis and Treatment of Pseudomonas aeruginosa Infections: An Update.

Pseudomonas aeruginosa is a Gram-negative bacterial pathogen that is a common cause of nosocomial infections, particularly pneumonia, infection in immunocompromised hosts, and in those with structural lung disease such as cystic fibrosis. Epidemiological studies have identified increasing trends of antimicrobial resistance, including multi-drug resistant (MDR) isolates in recent years. P. aeruginosa has several virulence mechanisms that increase its ability to cause severe infections, such as secreted toxins, quorum sensing and biofilm formation. Management of P. aeruginosa infections focuses on prevention when possible, obtaining cultures, and prompt initiation of antimicrobial therapy, occasionally with combination therapy depending on the clinical scenario to ensure activity against P. aeruginosa. Newer anti-pseudomonal antibiotics are available and are increasingly being used in the management of MDR P. aeruginosa.

Assessment of the In Vitro and In Vivo Antifungal Activity of NSC319726 against Candida auris.

Candida auris is an emerging yeast pathogen of candidemia with the ability to develop resistance to all current antifungal drug classes. Novel antifungal therapies against C. auris are warranted. NSC319726 is a thiosemicarbazone with an inhibitory effect on fungal ribosome biogenesis that has demonstrated some antifungal activity. In this study, we assessed the in vitro activity and in vivo efficacy of NSC319726 against C. auris. NSC319726 was active in vitro against 22 C. auris isolates from different clades, with MICs ranging from 0.125 to 0.25 mg/liter. Despite complete visual growth inhibition, the effect was described as fungistatic in time-kill curves. Interactions with fluconazole, amphotericin B, and micafungin, as tested by the checkerboard dilution method, were described as indifferent. NSC319726 demonstrated significant effects in rescuing G. mellonella larvae infected with two distinct C. auris isolates, compared to the untreated group. In conclusion, NSC319726 demonstrated in vitro activity against C. auris and in vivo efficacy in an invertebrate model of infection. Its potential role as a novel antifungal therapy in humans should be further investigated. IMPORTANCE Candida auris is emerging as a major public health threat because of its ability to cause nosocomial outbreaks of severe invasive candidiasis. Management of C. auris infection is difficult because of its frequent multidrug-resistant profile for currently licensed antifungals. Here, we show that the thiosemicarbazone NSC319726 was active in vitro against a large collection of C. auris isolates from different clades. Moreover, the drug was well tolerated and effective for the treatment of C. auris infection in an invertebrate model of Galleria mellonella. We conclude that NSC319726 might represent an interesting drug candidate for the treatment of C. auris infection.

Probabilistic modelling of effects of antibiotics and calendar time on transmission of healthcare-associated infection.

Healthcare-associated infection and antimicrobial resistance are major concerns. However, the extent to which antibiotic exposure affects transmission and detection of infections such as MRSA is unclear. Additionally, temporal trends are typically reported in terms of changes in incidence, rather than analysing underling transmission processes. We present a data-augmented Markov chain Monte Carlo approach for inferring changing transmission parameters over time, screening test sensitivity, and the effect of antibiotics on detection and transmission. We expand a basic model to allow use of typing information when inferring sources of infections. Using simulated data, we show that the algorithms are accurate, well-calibrated and able to identify antibiotic effects in sufficiently large datasets. We apply the models to study MRSA transmission in an intensive care unit in Oxford, UK with 7924 admissions over 10 years. We find that falls in MRSA incidence over time were associated with decreases in both the number of patients admitted to the ICU colonised with MRSA and in transmission rates. In our inference model, the data were not informative about the effect of antibiotics on risk of transmission or acquisition of MRSA, a consequence of the limited number of possible transmission events in the data. Our approach has potential to be applied to a range of healthcare-associated infections and settings and could be applied to study the impact of other potential risk factors for transmission. Evidence generated could be used to direct infection control interventions.

Nosocomial infections as one of the most important problems of healthcare system.

Healthcare-associated infections (HAI) are commonly defined as adverse events resulting from the provision of healthcare. The reduction of risk arising from the spread of pathogenic microorganisms in the hospital environment is a considerable challenge in the context of the proper functioning of the medical services sector. The financial costs of hospitals resulting from HAI are a serious problem for the Polish healthcare system. The spread of strains with a high level of drug resistance in individual hospitals is associated with the local epidemiological situation. In 2015-2017, there was a high increase in the number of infections caused by New Delhi strains. The highest increase due to this strain occurred in Mazowieckie and Podlasie provinces. The dynamics of infection caused by New Delhi strains throughout Poland in 2015-2016 indicated an increase of 278.7%. In 2017, the phenomenon of antibiotic abuse in all regions of Poland was 24% higher than the EU average. One of the reasons is the insufficient number of diagnostic tests ordered by both general practitioners and doctors representing hospital care. In 2016-2017, the average number of microbiological tests in diagnosing hospital infections performed annually within the entire territory of Poland was 50% lower than in European Union countries and the number recommended by WHO. Increased, and at the same time inappropriate antibiotic therapy led to a build-upof drug resistance among bacterial species of significant clinical importance. The current epidemiological situation imposes the necessity for constant HAI control and broadly understood rationalization of the guidelines of hospital antibiotic policy.

Antibiotic treatment protocols revisited: the challenges of a conclusive assessment by mathematical modelling.

Hospital-acquired bacterial infections lead to prolonged hospital stays and increased mortality. The problem is exacerbated by antibiotic-resistant strains that delay or impede effective treatment. To ensure successful therapy and to manage antibiotic resistance, treatment protocols that draw on several different antibiotics might be used. This includes the administration of drug cocktails to individual patients (combination therapy) but also the random assignment of drugs to different patients (mixing) and a regular switch in the default drug used in the hospital from drug A to drug B and back (cycling). For more than 20 years, mathematical models have been used to assess the prospects of antibiotic combination therapy, mixing and cycling. But while tendencies in their ranking across studies have emerged, the picture remains surprisingly inconclusive and incomplete. In this article, we review existing modelling studies and demonstrate by means of examples how methodological factors complicate the emergence of a consistent picture. These factors include the choice of the criterion by which the effects of the protocols are compared, the model implementation and its analysis. We thereafter discuss how progress can be made and suggest future modelling directions.

Optimizing Meropenem Therapy for Severe Nosocomial Infections in Neonates.

Meropenem pharmacokinetics in neonates exhibits large interindividual variability due to developmental changes occurring during the first month of life. The objective was to characterize meropenem pharmacokinetics through a population approach to determine effective dosing recommendations in neonates with severe nosocomial infections. Three blood samples from forty neonates were obtained once steady-state blood levels were achieved and plasma concentrations were determined with a validated chromatographic method. Data were used to develop and validate the one-compartment with first-order elimination population pharmacokinetic model obtained by non-linear mixed effect modeling. The final model was Clearance (L/h) = 2.23 × Creatinine Clearance (L/h) and Volume of distribution(L) = 6.06 × Body Surface Area(m2) × (1 + 0.60 if Fluticasone comedication). Doses should be adjusted based on said covariates to increase the likelihood of achieving therapeutic targets. This model explains 12.9% of the interindividual variability for meropenem clearance and 19.1% for volume of distribution. Stochastic simulations to establish initial dosing regimens to maximize the time above the MIC showed that the mean probabilities to achieve the PK/PD target (PTA) for microorganisms with a MIC of 2 and 8 µg/mL were 0.8 and 0.7 following i.v. bolus of 250 and 500 mg/m2/dose q8h, respectively. Meropenem extended 4h infusion would improve PTA in neonates with augmented creatinine clearance.

The healthcare costs of antimicrobial resistance in Lebanon: a multi-centre prospective cohort study from the payer perspective.

BACKGROUND: Our aim was to examine whether the length of stay, hospital charges and in-hospital mortality attributable to healthcare- and community-associated infections due to antimicrobial-resistant bacteria were higher compared with those due to susceptible bacteria in the Lebanese healthcare settings using different methodology of analysis from the payer perspective . METHODS: We performed a multi-centre prospective cohort study in ten hospitals across Lebanon. The sample size consisted of 1289 patients with documented healthcare-associated infection (HAI) or community-associated infection (CAI). We conducted three separate analysis to adjust for confounders and time-dependent bias: (1) Post-HAIs in which we included the excess LOS and hospital charges incurred after infection and (2) Matched cohort, in which we matched the patients based on propensity score estimates (3) The conventional method, in which we considered the entire hospital stay and allocated charges attributable to CAI. The linear regression models accounted for multiple confounders. RESULTS: HAIs and CAIs with resistant versus susceptible bacteria were associated with a significant excess length of hospital stay (2.69 days [95% CI,1.5-3.9]; p < 0.001) and (2.2 days [95% CI,1.2-3.3]; p < 0.001) and resulted in additional hospital charges ($1807 [95% CI, 1046-2569]; p < 0.001) and ($889 [95% CI, 378-1400]; p = 0.001) respectively. Compared with the post-HAIs analysis, the matched cohort method showed a reduction by 26 and 13% in hospital charges and LOS estimates respectively. Infections with resistant bacteria did not decrease the time to in-hospital mortality, for both healthcare- or community-associated infections. Resistant cases in the post-HAIs analysis showed a significantly higher risk of in-hospital mortality (odds ratio, 0.517 [95% CI, 0.327-0.820]; p = 0.05). CONCLUSION: This is the first nationwide study that quantifies the healthcare costs of antimicrobial resistance in Lebanon. For cases with HAIs, matched cohort analysis showed more conservative estimates compared with post-HAIs method. The differences in estimates highlight the need for a unified methodology to estimate the burden of antimicrobial resistance in order to accurately advise health policy makers and prioritize resources expenditure.

Healthcare-Associated Infections and Antibiotics Consumption: A Comparison of Point Prevalence Studies and Intervention Strategies.

This study compares healthcare-associated infections (HAIs) prevalence and antimicrobial consumption (AMC) from surveys conducted in 2016 and 2019 in an Italian hospital for acute care. HAIs prevalence was 7.1% in both surveys, while patients were under antibiotic treatment slightly increased from 2016 to 2019, from 42.6% to 43.7%, respectively. In the survey of 2016, HAIs risk factors were fatal McCabe score and hospitalization longer than two weeks, while CVC and urinary catheter in that conducted in 2019. In both surveys, CVC and peripheral venous catheter resulted associated to AMC. HAIs and AMC remained stable although the hospital undergone a complexity reduction in the second survey, remarking that critical actions are strictly required implementing infection control practices and antimicrobial stewardship.

Investigation of Acinetobacter baumannii Activity in Vascular Surgery Units through Epidemiological Management Based on the Analysis of Antimicrobial Resistance, Biofilm Formation and Genotyping.

BACKGROUND/OBJECTIVES: The genus Acinetobacter demonstrates resistance to antibiotics and has been shown to spread in the hospital environment causing epidemic outbreaks among hospitalized patients. The objectives of the present study was to investigate the antibiotic resistance, biofilm formation, and clonality among Acinetobacter baumannii strains. MATERIALS AND METHODS: The study involved 6 (I Outbreak) and 3 (II Outbreak) A. baumannii strains isolated from patients hospitalized in vascular surgery unit. RESULTS: All tested A. baumannii strains were extensively drug resistant (XDR) and all the isolates were carbapenem-resistant and among them, all carried the blaOXA-51 gene, the blaOXA-24 gene, as well as the blaOXA-23 gene. All of the investigated strains had the ability to form a biofilm, but all of them produced less biofilm than the reference strain. Multi-locus sequence typing (MLST) showed that all strains belonged to the ST2 clone. Pulsed-field gel electrophoresis (PFGE) divided the tested outbreak strains into two clones (A and B). CONCLUSION: This study shows a nosocomial spread of XDR A. baumannii ST2 having the blaOXA-51 gene, the blaOXA-24 gene, as well as the blaOXA-23 gene, low biofilm formers, that was prevalent in the vascular surgery unit. To identify the current situation of vascular surgery departments targeted epidemiological investigation was needed. Effective implementation of infection control prevented the spread of the epidemic outbreaks.