Influence of Rational use of Antibacterial Drugs on Drug Resistance of Pathogenic Bacteria in Nosocomial Infection.

The purpose of this study is to explore the impact of multi-departmental linkage and rational drug use supervision on the drug resistance of pathogenic bacteria in primary hospitals. Use the method of pharmacies and infection control departments to jointly develop hospital antimicrobial usage guidelines and reward and punishment systems to promote the rational use of antimicrobial drugs. In addition, clinicians and clinical pharmacists of the pharmacy department participated in the formulation of anti-infection programs, infection control departments and pharmacy supervision, and compared the rational use of antibacterial drugs, the time of antibacterial drug use, and the detection of drug-resistant bacteria between the two groups before and after the implementation of the mechanism. Our results showed that the rational use rates of medication indications, drug selection, drug dosage, and medication course in the observation group were 97.74%, 96.99%, 98.50%, and 96.24%, respectively, which were higher than 79.71% in the control group, 76.81%, 72.46% and 75.36%, the difference was statistically significant (P < .05); there was no statistically significant difference in the rational utilization rate of drug administration routes between the two groups (P > .05). The antibacterial drug use time of the observation group was (7.39±1.84) d shorter than that of the control group (13.53±2.61) d, and the difference was statistically significant (P < .05). The detection rate of drug-resistant bacteria in the observation group was 24.44%, which was lower than 42.86% in the control group, and the difference was statistically significant (P < .05). This shows that the grassroots multi-department linkage supervision mechanism is in line with the management model of standardizing the rational use of antimicrobial drugs at the grassroots level, and the intervention in the application of antibacterial drugs is conducive to improving the knowledge reserve of drug use among the grassroots people. The economic cost of reducing drug-resistant bacteria is huge. In addition to death and disability, long-term illness can result in longer hospital stays, the need for more expensive medications, and a significant financial burden on those affected. Therefore, improving the rationality of clinicians' medication use will help shorten treatment time and reduce drug-resistant bacteria. It is worthy of clinical promotion and application.

Antibacterial Effects of Chloroform Henna (Lawsonia inermis) Leaf Extracts against Two Nosocomial Infection Causing Pathogens: Gram-positive Staphylococcus aureus and Gram-negative Klebsiella pneumoniae: A Comparative Study.

Evaluation of the in vitro antibacterial activity of Chloroform extracts isolated from Henna (Lawsonia inermis) leaf against two nosocomial infection causing pathogens, gram-positive Staphylococcus aureus and gram-negative Klebsiella pneumoniae. This interventional study was carried out for the period of January 2021 to December 2021 in the Department of Pharmacology and Therapeutics in collaboration with the Department of Microbiology, Mymensingh Medical College, Bangladesh. The antibacterial activity was tested at different concentrations of Chloroform Henna leaf extracts by using disc diffusion and broth dilution method. The extract was prepared by using solvents chloroform and 0.1% Dimethyl sulfoxide (DMSO). The test microorganisms were also tested for their activity against a standard antibiotic Ciprofloxacin by broth dilution method and the result was compared with that of Chloroform extracts. Chloroform Henna Extracts (CHE) were used initially in nine different concentrations (2.5, 5, 10, 20, 50, 100, 200, 500 and 1000 mg/ml). Among different concentrations of the CHE, 100mg/ml and above concentrations showed inhibitory effect against Staphylococcus aureus and Klebsiella pneumoniae. The MIC for Staphylococcus aureus and Klebsiella pneumoniae were 100 and 200mg/ml in CHE respectively. The MIC of Ciprofloxacin was 1µg/ml against Staphylococcus aureus and 1.5µg/ml against Klebsiella pneumoniae. The MIC of Ciprofloxacin was the lowest in comparison to MICs of CHE for the test organisms. This study showed that Chloroform Henna extracts demonstrated antibacterial effects against food borne pathogens. It is clearly observed that there is definite antibacterial effect of the Chloroform extract of Henna leaves (Lawsonia inermis) against Staphylococcus aureus and Klebsiella pneumoniae.

Identification of an Outbreak Cluster of Extensively Antibiotic-Resistant GC1 Acinetobacter baumannii Isolates in U.S. Military Treatment Facilities.

An outbreak involving an extensively antibiotic-resistant Acinetobacter baumannii strain in three military treatment facilities was identified. Fifty-nine isolates recovered from 30 patients over a 4-year period were found among a large collection of isolates using core genome multilocus sequence typing (MLST). They differed by only 0 to 18 single nucleotide polymorphisms (SNPs) and carried the same resistance determinants except that the aphA6 gene was missing in 25 isolates. They represent a novel sublineage of GC1 lineage 1 that likely originated in Afghanistan. IMPORTANCE A. baumannii is recognized as one of the most important nosocomial pathogens, and carbapenem-resistant strains pose a particularly difficult treatment challenge. Outbreaks linked to this pathogen are reported worldwide, particularly during periods of societal upheaval, such as natural disasters and conflicts. Understanding how this organism enters and establishes itself within the hospital environment is key to interrupting transmission, but few genomic studies have examined these transmissions over a prolonged period. Though historical, this report provides an in-depth analysis of nosocomial transmission of this organism across continents and within and between different hospitals.

Optimization of polymyxin B regimens for the treatment of carbapenem-resistant organism nosocomial pneumonia: a real-world prospective study.

BACKGROUND: Polymyxin B is the first-line therapy for Carbapenem-resistant organism (CRO) nosocomial pneumonia. However, clinical data for its pharmacokinetic/pharmacodynamic (PK/PD) relationship are limited. This study aimed to investigate the relationship between polymyxin B exposure and efficacy for the treatment of CRO pneumonia in critically ill patients, and to optimize the individual dosing regimens. METHODS: Patients treated with polymyxin B for CRO pneumonia were enrolled. Blood samples were assayed using a validated high-performance liquid chromatography-tandem mass spectrometry method. Population PK analysis and Monte Carlo simulation were performed using Phoenix NLME software. Logistic regression analyses and receiver operating characteristic (ROC) curve were employed to identify the significant predictors and PK/PD indices of polymyxin B efficacy. RESULTS: A total of 105 patients were included, and the population PK model was developed based on 295 plasma concentrations. AUCss,24 h/MIC (AOR = 0.97, 95% CI 0.95-0.99, p = 0.009), daily dose (AOR = 0.98, 95% CI 0.97-0.99, p = 0.028), and combination of inhaled polymyxin B (AOR = 0.32, 95% CI 0.11-0.94, p = 0.039) were independent risk factors for polymyxin B efficacy. ROC curve showed that AUCss,24 h/MIC is the most predictive PK/PD index of polymyxin B for the treatment of nosocomial pneumonia caused by CRO, and the optimal cutoff point value was 66.9 in patients receiving combination therapy with another antimicrobial. Model-based simulation suggests that the maintaining daily dose of 75 and 100 mg Q12 h could achieve ≥ 90% PTA of this clinical target at MIC values ≤ 0.5 and 1 mg/L, respectively. For patients unable to achieve the target concentration by intravenous administration, adjunctive inhalation of polymyxin B would be beneficial. CONCLUSIONS: For CRO pneumonia, daily dose of 75 and 100 mg Q12 h was recommended for clinical efficacy. Inhalation of polymyxin B is beneficial for patients who cannot achieve the target concentration by intravenous administration.

Multi-drug resistant ESKAPE pathogens and the uses of plants as their antimicrobial agents.

Infections by ESKAPE (Enterococcus sp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pathogens cause major concern due to their multi-drug resistance (MDR). The ESKAPE pathogens are frequently linked to greater mortality, diseases, and economic burden in healthcare worldwide. Therefore, the use of plants as a natural source of antimicrobial agents provide a solution as they are easily available and safe to use. These natural drugs can also be enhanced by incorporating silver nanoparticles and combining them with existing antibiotics. By focussing the attention on the ESKAPE organisms, the MDR issue can be addressed much better.

The treatment of nosocomial meningitis and brain abscess by carbapenem-resistant Klebsiella pneumonia.

We report the fourth case of Carbapenem-resistant Klebsiella pneumoniae (CRKP) meningitis and the only one associated with brain abscess formation. A 29-years-old male patient developed septic shock 13 days after a right nasopharyngeal AVM resection. CRKP was grown from CSF with a MIC for meropenem ≥16 mg/L. Intravenous tigecycline and amikacin, combined with intrathecal amikacin and oral sulfamethoxazole were given. CSF culture was sterile on the 23rd day post operation. A right temporal lobe brain abscess formed by day 38 and was drained. Antibiotics were changed to oral sulfamethoxazole and minocycline for four weeks. The patient was cured with no relapse to date. With few cases reported we can only carefully recommend the combinational use of intravenous antibiotics with high dose intrathecal/intraventricular aminoglycosides.

Clinical Feature, Therapy, Antimicrobial Resistance Gene Distribution, and Outcome of Nosocomial Meningitis Induced by Multidrug-Resistant Enterobacteriaceae-A Longitudinal Cohort Study From Two Neurosurgical Centers in Northern China.

Objectives: This is a comparative cohort study aiming to evaluate the mortality risk factors for patients with nosocomial meningitis (NM) induced by multidrug-resistant Enterobacteriaceae (MDRE) in China. The clinical features and therapies of patients and the resistance mechanisms of MDRE pathogens were also assessed. Methods: MDRE-NM patients from two neurosurgical centers in China from 2014 to 2019 were included in this study. Clinical features were extracted from the medical record databases of the two centers. The molecular mechanisms underlying the microbiological resistance mechanisms of each MDRE pathogen were determined, Kaplan-Meier survival analysis was conducted, and multivariable analyses were performed using a Cox proportional hazard model. Results: Ninety MDRE-NM patients were included in this study. Klebsiella pneumoniae accounted for the highest proportion of causative pathogens (46/90, 51.1%), and 40 causative pathogens (44.4%) were meropenem-resistant. blaKPC (27/40, 67.5%) was the predominant carbapenem resistance gene. Multivariate Cox analysis showed that external ventricular drainage (EVD) [hazard ratio (HR) = 2.524, 95% confidence interval (CI) = 1.101-5.787, p = 0.029] and a Glasgow Coma Scale (GCS) score ≤;8 (HR = 4.033, 95% CI = 1.526-10.645, p = 0.005) were mortality risk factors for patients with MDRE-NM. A total of 90.0%, 94.4%, and 97.8% of MDRE-NM patients received antibiotic prophylaxis (AP), antibiotic empirical therapy (AET), and antibiotic definitive therapy (ADT), respectively. Conclusions: NM caused by MDRE is an important sign of the failure of neurosurgery. MDRE possesses multiple drug resistance genotypes, and EVD and a GCS score ≤;8 are independent mortality risk factors for patients with MDRE-NM, which deserve the attention of microbiologists and neurosurgical clinicians.

Rationalising empirical antibiotics for bloodstream infections: A retrospective study at a South African district-level hospital.

BACKGROUND: Incorrect empirical antibiotic therapy is one of the factors that contribute to poor clinical outcomes and the development of antimicrobial resistance. Knowledge of the local infectious disease burden and antibiotic resistance patterns can assist with development of strategies, updating of guidelines and subsequent improvement in initial empirical therapy. OBJECTIVES: To determine whether the empirical antibiotic choice for treatment of septic episodes at a district-level hospital was appropriate according to national guidelines, and to describe the epidemiological features of the septic episode population being studied and depict their antibiotic susceptibility profile. METHODS: This was a retrospective, descriptive study of adult inpatients with bloodstream infections at Karl Bremer Hospital, Cape Town, South Africa. Laboratory and clinical data were obtained and analysed for the period 1 July 2017 - 30 June 2018. Septic episodes were subdivided into community-acquired bloodstream infection (CABSI) and hospital-acquired bloodstream infection (HABSI) study populations, and empirical antibiotics for both groups were assessed and compared with the adult Standard Treatment Guidelines and Essential Medicines List for South Africa, Hospital Level Care, 2015 edition (STG and EML). RESULTS: Our study sample consisted of 184 septic episodes, isolated from 176 patients. Nearly half of the septic episodes (49.5%) were hospital acquired. Overall guideline adherence in the CABSI population was 88%, compared with 58% in the HABSI population. The reasons for guideline non-adherence in the CABSI population were lack of source-appropriate empirical antibiotics (n=7) and septic episodes where empirical antibiotics were indicated but not prescribed (n=4), while in the HABSI group the main reason was that the patients were treated by community-acquired standards (n=30; 33.0%). The in-hospital mortality rate for a septic episode in this study was 38%. Considering the typical first-line antibiotics used, 77.3% of CABSIs were found to be susceptible to co-amoxiclav (n=75) and 59.8% to ceftriaxone (n=58). With the exclusion of methicillin-resistant Staphylococcus aureus and Acinetobacter baumannii isolates as confounders, HABSIs had a susceptibility of 86% to the piperacillin/tazobactam plus amikacin combination, 81% to ertapenem, 90% to imipenem and 93% to meropenem. CONCLUSIONS: This study demonstrates poor guideline adherence in HABSIs, emphasising the importance of distinguishing between CABSIs and HABSIs. The empirical antibiotics advised by the STG and EML were found to be appropriate in the majority of septic episodes. Future revision and improvement of prescribing practices can assist in rationalising empirical antibiotic decisions.

Iron serum levels and iron homeostasis parameters in patients with nosocomial pneumonia treated with cefiderocol: post hoc analysis of the APEKS-NP study.

Critically ill patients often present with low serum iron levels or anemia. We evaluated the impact of iron levels and iron homeostasis on the efficacy and safety of cefiderocol, an iron-chelator siderophore cephalosporin, in patients with nosocomial pneumonia in a post hoc analysis of the randomized, double-blind, Phase 3 APEKS-NP study (NCT03032380). Patients with Gram-negative nosocomial pneumonia received cefiderocol 2 g, 3-h infusion, q8h, or high-dose, extended-infusion meropenem 2 g, 3-h infusion, q8h, for 7-14 days. Efficacy and safety parameters, including specific iron homeostasis parameters (i.e., hepcidin, iron, total iron binding capacity, transferrin saturation), were analyzed according to baseline iron levels. In the cefiderocol and meropenem arms, 79.1% (117/148) and 83.3% (125/150) randomized patients, respectively, had low baseline serum iron levels. Rates of 14-day (12.3% [14/114] vs 11.6% [14/121]) and 28-day all-cause mortality (20.5% [23/112] vs 19.0% [23/121]), clinical cure (63.2% [72/114] vs 67.2% [82/122]), and microbiological eradication (43.6% [41/94] vs 48.1% [51/106]) at test of cure were similar in cefiderocol vs meropenem arms, respectively. In the overall safety population, rates of anemia-related adverse events were similar (cefiderocol arm 18.2% [27/148], meropenem arm 18.7% [28/150]). Changes from baseline to test of cure in hepcidin, iron, total iron binding capacity, and transferrin saturation were similar between treatment arms. Cefiderocol treatment did not affect iron homeostasis, and its efficacy and safety were not influenced by baseline serum iron levels. Clinicaltrials.gov registration: NCT03032380. Date of registration: 26 January 2017.

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.

Antimicrobial resistance profiles and associated factors of Acinetobacter and Pseudomonas aeruginosa nosocomial infection among patients admitted at Dessie comprehensive specialized Hospital, North-East Ethiopia. A cross-sectional study.

INTRODUCTION: Hospital admitted patients are at increased risk of nosocomial infections (NIs) with multi-drug resistant (MDR) pathogens which are prevalent in the hospital environment. Pseudomonas aeruginosa (P. aeruginosa) and Acinetobacter baumannii (A. baumannii) are common causes of NIs worldwide. The objective of this study is to determine antimicrobial resistance profiles and associated factors of Acinetobacter spp and P. aeruginosa NIs among hospitalized patients. METHODS: A cross-sectional study was conducted at Dessie comprehensive specialized hospital, North-East Ethiopia, from February 1 to April 30, 2020. A total of 254 patients who were suspected of the bloodstream, urinary tract, or surgical site nosocomial infections were enrolled consecutively. Socio-demographic and other variables of interest were collected using a structured questionnaire. Specimens were collected and processed following standard microbiological procedures. Antimicrobial susceptibility was determined using the Kirby-Bauer disk diffusion method following Clinical and Laboratory Standards Institute guidelines. Data were analyzed with SPSS version 23 and p-value < 0.05 was considered statistically significant. RESULTS: Overall, 13% of patients had nosocomial Acinetobacter spp and/or P. aeruginosa infections. The culture positivity rate was 16(6.3%) for Acinetobacter spp and 18(7.1%) for P. aeruginosa. Patients admitted in the surgical ward (Adjusted odds ratio (AOR):10.66;95% confidence interval (CI):1.22-93.23), pediatric ward (AOR:14.37;95%CI:1.4-148.5), intensive care unit (AOR:41.93;95%CI:4.7-374.7) and orthopedics (AOR:52.21;95%CI:7.5-365) were significantly at risk to develop NIs compared to patients admitted in the medical ward. Patients who took more than two antimicrobial types at admission were 94% (AOR:0.06; 95% CI:0.004-0.84) times more protected from NIs compared to those who did not take any antimicrobial. About 81% of Acinetobacter spp and 83% of P. aeruginosa isolates were MDR. Amikacin and meropenem showed promising activity against Acinetobacter spp and P. aeruginosa isolates. CONCLUSION: The high prevalence of MDR Acinetobacter spp and P. aeruginosa nosocomial isolates enforce treating of patients with NIs based on antimicrobial susceptibility testing results.

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.

Antimicrobial use for treatment of healthcare-associated infections and bacterial resistance in a reference neonatal unit

Abstract Objective The use of broad-spectrum antimicrobials, such as third and fourth-generation, are responsible for emergence of multidrug-resistant microorganisms in neonatal units. Furthermore, antimicrobial daily doses are not standardized in neonatology. This study aimed to investigate the association between the use of antimicrobial broad spectrum to bacterial sensitivity profile in a referral unit of neonatal progressive care. Methods This is a cohort study conducted in a referral neonatal progressive care unit from January 2008 to December 2016. The data of all hospitalized neonates was collected daily. The infection criteria used were the standardized national criteria, based on definitions of Center for Diseases Control and Prevention. In this study, the use of antimicrobials was evaluated as antimicrobial-day (ATM-day) and the ratio of multidrug-resistant microorganisms per 1000 ATM-day of broad spectrum was also calculated. The study was approved by the Institutional Review Board of the Universidade Federal de Minas Gerais (ETIC 312/08 e CAAE 58973616.2.0000.5149). Results From 2008 to 2016, 2751 neonates were hospitalized, corresponding to 60,656 patient-days. The ratio of multidrug-resistant microorganisms per 1000 ATM-day of broad spectrum was 1,3 in the first period and 4,3 in the second period (p = 0,005). Conclusion It was observed that use of broad-spectrum antimicrobials, especially those with coverage for Gram-negative bacteria, was associated with an increase of multidrug-resistant bacteria.

A Japanese traditional medicine Hochuekkito promotes negative conversion of vancomycin-resistant Enterococci.

Vancomycin-resistant enterococci (VRE) are prominent causes of nosocomial infections. Japanese traditional (Kampo) medicine promotes intestinal immunity and protects against bacterial infections. We assessed potential differences in the clinical course of VRE-positive patients, based on their characteristics and treatment with Kampo medicines. This retrospective observational study collected data from VRE-positive patients from August 2018 to July 2019 at a tertiary-care hospital in Japan. The data of 122 consecutive VRE-positive inpatients were analyzed. Sixty-nine patients were treated with probiotics, among whom, 18 were further treated with Kampo medicines. Twenty-six of the 122 patients subsequently died. In univariate analyses, subsequent VRE negative conversion significantly reduced the mortality of VRE-detected patients (p = .0003). Administration of probiotics (p = .0065) and Kampo medicines with probiotics (p = .0002), especially of the Kampo medicine hochuekkito (p = .0014), and a higher serum albumin level positively contributed to the subsequent VRE negative conversion. Multivariate analyses demonstrated that Kampo medicines and body mass index contributed to VRE negative conversion. Hochuekkito shortened the time needed for VRE negative conversion (p = 0.0485). Administration of Kampo medicines, especially of hochuekkito, in addition to probiotics in VRE patients may promote VRE negative conversion.

The pathogenic characteristics and influencing factors of health care-associated infection in elderly care center under the mode of integration of medical care and elderly care service: A cross-sectional study.

ABSTRACT: The aim of this study was to analyze the distribution of pathogenic bacteria in hospitalized patients in elderly care centers under the mode of integration of medical care and elderly care service, and explore the influencing factors to reduce the health care-associated infection rate of hospitalized patients.A total of 2597 inpatients admitted to elderly care centers from April 2018 to December 2019 were included in the study. The etiology characteristics of health care-associated infections (HCAI) was statistically analyzed, univariate analysis, and multivariate logistic regression analysis method were used to analyze the influencing factors of HCAI.A total of 98 of 2597 inpatients in the elderly care centers had HCAI, and the infection rate was 3.77%. The infection sites were mainly in the lower respiratory tract and urinary tract, accounting for 53.92% and 18.63%, respectively. A total of 53 pathogenic bacteria were isolated, 43 of which (81.13%) were Gram-negative, mainly Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, which respectively accounted for 24.53, 16.98, and 13.21%. 9 (16.98%) strains were Gram-positive, mainly Staphylococcus aureus and Enterococcus faecium, respectively accounting for 7.55 and 5.66%. Only 1 patient (1.89%) had a fungal infection. Multivariate logistic regression analysis indicated that total hospitalization days, antibiotic agents used, days of central line catheter, use of urinary catheter and diabetes were independent risk factors of nosocomial infection in elderly care centers (P < .05).Many factors can lead to nosocomial infections in elderly care centers. Medical staff should take effective intervention measures according to the influencing factors to reduce the risk of infection in elderly care facilities.

Epidemiology, species distribution, and outcome of nosocomial Candida spp. bloodstream infection in Shanghai: an 11-year retrospective analysis in a tertiary care hospital.

BACKGROUND: The incidence of Candida bloodstream infections (BSIs), has increased over time. In this study, we aimed to describe the current epidemiology of Candida BSI in a large tertiary care hospital in Shanghai and to determine the risk factors of 28-day mortality and the impact of antifungal therapy on clinical outcomes. METHODS: All consecutive adult inpatients with Candida BSI at Ruijin Hospital between January 1, 2008, and December 31, 2018, were enrolled. Underlying diseases, clinical severity, species distribution, antifungal therapy, and their impact on the outcomes were analyzed. RESULTS: Among the 370 inpatients with 393 consecutive episodes of Candida BSI, the incidence of nosocomial Candida BSI was 0.39 episodes/1000 hospitalized patients. Of the 393 cases, 299 (76.1%) were treated with antifungal therapy (247 and 52 were treated with early appropriate and targeted antifungal therapy, respectively). The overall 28-day mortality rate was 28.5%, which was significantly lower in those who received early appropriate (25.5%) or targeted (23.1%) antifungal therapy than in those who did not (39.4%; P = 0.012 and P = 0.046, respectively). In multivariate Cox regression analysis, age, chronic renal failure, mechanical ventilation, and severe neutropenia were found to be independent risk factors of the 28-day mortality rate. Patients who received antifungal therapy had a lower mortality risk than did those who did not. CONCLUSIONS: The incidence of Candida BSI has increased steadily in the past 11 years at our tertiary care hospital in Shanghai. Antifungal therapy influenced short-term survival, but no significant difference in mortality was observed between patients who received early appropriate and targeted antifungal therapy.

Multidrug-resistant Klebsiella pneumoniae harboring extended spectrum ß-lactamase encoding genes isolated from human septicemias.

Klebsiella pneumoniae is a major pathogen implicated in nosocomial infections. Extended-spectrum ß-lactamase (ESBL)-producing K. pneumoniae isolates are a public health concern. We aim to characterize the type of ß-lactamases and the associated resistance mechanisms in ESBL-producing K. pneumoniae isolates obtained from blood cultures in a Portuguese hospital, as well as to determine the circulating clones. Twenty-two cefotaxime/ceftazidime-resistant (CTX/CAZR) K. pneumoniae isolates were included in the study. Identification was performed by MALDI-TOF MS and the antimicrobial susceptibility testing by disk-diffusion. The screening test for ESBL-production was performed and ESBL-producer isolates were further characterized. The presence of different beta-lactamase genes (blaCTX-M, blaSHV, blaTEM, blaKPC, blaNDM, blaVIM, blaOXA-48, blaCMY-2, blaDHA-1, blaFOX, blaMOX, and blaACC) was analyzed by PCR/sequencing in ESBL-producer isolates, as well as the presence of other resistance genes (aac(6')-Ib-cr, tetA/B, dfrA, qnrA/B/S, sul1/2/3) or integron-related genes (int1/2/3). Multilocus-sequence-typing (MLST) was performed for selected isolates. ESBL activity was detected in 12 of the 22 CTX/CAZR K. pneumoniae isolates and 11 of them carried the blaCTX-M-15 gene (together with blaTEM), and the remaining isolate carried the blaSHV-106 gene. All the blaCTX-M-15 harboring isolates also contained a blaSHV gene (blaSHV-1, blaSHV-11 or blaSHV-27 variants). Both blaSHV-27 and blaSHV-106 genes correspond to ESBL-variants. Two of the CTX-M-15 producing isolates carried a carbapenemase gene (blaKPC2/3 and blaOXA-48) and showed imipenem resistance. The majority of the ESBL-producing isolates carried the int1 gene, as well as sulphonamide-resistance genes (sul2 and/or sul3); the tetA gene was detected in all eight tetracycline-resistant isolates. Three different genetic lineages were found in selected isolates: ST348 (one CTX-M-15/TEM/SHV-27/KPC-2/3-producer isolate), ST11 (two CTX-M-15/TEM/SHV-1- and CTX-M-15-TEM-SHV-11-OXA-48-producer isolates) and ST15 (one SHV-106/TEM-producer isolate). ESBL enzymes of CTX-M-15 or SHV-type are detected among blood K. pneumoniae isolates, in some cases in association with carbapenemases of KPC or OXA-48 type.

Successful Treatment of Klebsiella pneumoniae NDM Sepsis and Intestinal Decolonization with Ceftazidime/Avibactam Plus Aztreonam Combination in a Patient with TTP Complicated by SARSCoV-2 Nosocomial Infection.

Carbapenem-resistant Enterobacteriaceae (CRE) are a serious public health threat. Infections due to these organisms are associated with significant morbidity and mortality. Among them, metallo-ß-lactamases (MBLs)-producing Klebsiella pneumoniae are of global concern today. The ceftazidime/avibactam combination and the ceftazidime/avibactam + aztreonam combination currently represent the most promising antibiotic strategies to stave off these kinds of infections. We describe the case of a patient affected by thrombotic thrombocytopenic purpura (TTP) admitted in our ICU after developing a hospital-acquired SarsCoV2 interstitial pneumonia during his stay in the hematology department. His medical conditions during his ICU stay were further complicated by a K. Pneumoniae NDM sepsis. To our knowledge, the patient had no risk factors for multidrug-resistant bacteria exposure or contamination during his stay in the hematology department. During his stay in the ICU, we treated the sepsis with a combination therapy of ceftazidime/avibactam + aztreonam. The therapy solved his septic state, allowing for a progressive improvement in his general condition. Moreover, we noticed that the negativization of the hemocultures was also associated to a decontamination of his known rectal colonization. The ceftazidime/avibactam + aztreonam treatment could not only be a valid therapeutic option for these kinds of infections, but it could also be considered as a useful tool in selected patients' intestinal decolonizations.

Caralluma europaea (Guss.) N.E.Br.: Anti-Inflammatory, Antifungal, and Antibacterial Activities against Nosocomial Antibiotic-Resistant Microbes of Chemically Characterized Fractions.

Caralluma europaea (Guss.) N.E.Br.: (C. europaea) is a wild medicinal plant belonging to the family Apocynaceae. It is commonly used in traditional medicines for treating several diseases. The present work aims to evaluate the anti-inflammatory, antibacterial, and antifungal potentials of C. europaea fractions including hydro ethanol (ET CE), n-butanol (But CE), and polyphenol (Poly CE). The chemical composition of hydroethanol, n-butanol, and polyphenol-rich fractions from C. europaea were determined using GC-MS after silylation. The anti-inflammatory effect of hydroethanol, n-butanol, and polyphenol-rich fractions was studied by carrageenan-induced paw edema. Antibacterial and antifungal activities of hydroethanol, n-butanol, and polyphenol-rich fractions against Gram-positive bacteria, Gram-negative bacteria, and yeasts were assessed using the disc diffusion and micro-dilution assays. The findings of the chemical characterization affirmed the presence of interesting bioactive compounds in C. europaea fractions. The polyphenol-rich fraction was the best inhibitor of edema by75.68% after 6 h of treatment. The hydroethanol fraction was the most active against both bacteria and yeasts. This study contributes to society as it provides potential bioactive compounds in C. europaea extract, which may help in fighting nosocomial antibiotic-resistant microbes.

Bloodstream infections caused by ST2 Acinetobacter baumannii: risk factors, antibiotic regimens, and virulence over 6 years period in China.

BACKGROUND: Bloodstream infection (BSI) caused by multidrug-resistant Acinetobacter baumannii (MDR-AB) has been increasingly observed among hospitalized patients. The following study analyzed the epidemiology and microbiological characteristics of MDR-AB, as well as the clinical features, antimicrobial treatments, and outcomes in patients over a six years period in China. METHODS: This retrospective study was conducted in a large tertiary hospital in China between January 2013 and December 2018. The clinical and microbiological data of all consecutive hospitalized patients with MDR-AB induced bloodstream infection were included and analyzed. RESULTS: A total of 108 BSI episodes were analyzed. All MDR isolates belonged to ST2, a sequence type that has spread all over the world. Overall, ST2 strains showed strong biofilm formation ability, high serum resistance, and high pathogenicity. As for the clinical characteristics of the patient, 30-day mortality was 69.4% (75/108). The three main risk factors included mechanical ventilation, intensive care unit (ICU) stay, and thrombocytopenia; three protective factors included a change of antimicrobial regimen within 48 h after positive blood culture, use of the antibacterial agent combination, and more inpatient days. The most effective antibacterial regimen was the combination of cefoperazone/sulbactam and tigecycline. CONCLUSIONS: BSI caused by ST2 A.baumannii represents a difficult challenge for physicians, considering the high mortality associated with this infection. The combination of cefoperazone/sulbactam and tigecycline may be an effective treatment option.