Septic cardiomyopathy phenotype in the critically ill may depend on antimicrobial resistance.

Background: Sepsis is a life-threatening organ dysfunction, and septic cardiomyopathy (SCM) may complicate the course of the disease. Infection with multidrug-resistant (MDR) pathogens has been linked with worse outcomes. This study aims to evaluate SCM in patients with infections caused by different antimicrobial-resistant phenotypes. Method: This retrospective study included patients with sepsis/septic shock, hospitalized, and intubated in the intensive care unit of the University Hospital of Larissa between January 2022 and September 2023 with echocardiographic data during the first two days after infection onset. The patients were divided into two groups: non-MDR-SCM group and MDR-SCM group. The cardiac function was compared between the two groups. Result: A total of 62 patients were included in the study. Forty-four patients comprised the MDR-SCM and 18 the non-MDR-SCM group. Twenty-six patients (41.9%) presented with left ventricular (LV) systolic dysfunction, and ≤35% right ventricular fractional area change (RVFAC) was present in 56.4%. LV systolic function was more severely impaired in the non-MDR-SCM group (left ventricular ejection fraction, 35.8% ±4.9% vs. 45.6%±2.4%, P=0.049; LV outflow tract velocity time integral, [10.1±1.4] cm vs. [15.3±0.74] cm, P=0.001; LV-Strain, -9.02%±0.9% vs. -14.02%±0.7%, P=0.001). The MDR-SCM group presented with more severe right ventricular (RV) dilatation (right ventricular end-diastolic area/left ventricular end-diastolic area, 0.81±0.03 vs. 0.7±0.05, P=0.042) and worse RV systolic function (RVFAC, 32.3%±1.9% vs. 39.6%±2.7%, P=0.035; tricuspid annular plane systolic excursion, [15.9±0.9] mm vs. [18.1±0.9] mm, P=0.165; systolic tissue Doppler velocity measured at the lateral tricuspid annulus, [9.9±0.5] cm/s vs. [13.1±0.8] cm/s, P=0.002; RV-strain, -11.1%±0.7% vs. -15.1%±0.9%, P=0.002). Conclusion: SCM related to MDR infection presents with RV systolic dysfunction predominance, while non-MDR-SCM is mainly depicted with LV systolic dysfunction impairment.

In Vitro antibiotic combinations of Colistin, Meropenem, Amikacin, and Amoxicillin/clavulanate against multidrug-resistant Klebsiella pneumonia isolated from patients with ventilator-associated pneumonia.

BACKGROUND: Hospital infections such as ventilator-associated pneumonia (VAP) due to multidrug-resistant Klebsiella pneumoniae (MDR-KP) strains have increased worldwide. In addition, biofilm production by these resistant isolates has confronted clinicians with higher treatment failure and infection recurrence. Given the paucity of new agents and limited data on combination therapy for MDR-KPs, the present study sought to evaluate the in vitro activity of several antibiotic combinations against planktonic and biofilm MDR-KPs isolated from patients with VAP. RESULTS: All 10 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates demonstrated multidrug resistance against the tested antibiotics. At planktonic mode, combinations of colistin-meropenem and amoxicillin/clavulanate in combination with meropenem, colistin, or amikacin showed synergism against 60-70% isolates. On the other hand, in the biofilm state, colistin-based combinations exhibited synergism against 50-70% isolates and the most effective combination was colistin-amikacin with 70% synergy. CONCLUSIONS: The results revealed that combinations of amoxicillin/clavulanate with colistin, meropenem, or amikacin in the planktonic mode and colistin with amoxicillin/clavulanate, meropenem, or amikacin in the biofilm mode could effectively inhibit CRKP isolates, and thus could be further explored for the treatment of CRKPs.

Evaluation of antibacterial efficacy of garlic (Allium sativum) and ginger (Zingiber officinale) crude extract against multidrug-resistant (MDR) poultry pathogen.

Objective: The study is aimed to understand the antibacterial sensitivity of native and Indian varieties of garlic (Allium sativum) and ginger (Zingiber officinale) crude extracts against multidrug-resistant (MDR) poultry pathogen (Escherichia coli and Salmonella sp.). Materials and Methods: Thin layer chromatography (TLC) is used to identify the target spices' bioactive antibacterial compounds. MDR E. coli and Salmonella sp. were isolated from poultry. The TLC-Bioautography technique was applied to explore the antibacterial potentiality of garlic and ginger. Results: Inhibitory activities of garlic were Zone of inhibition (ZI) = 14.03 ± 0.15 mm and 19.70 ± 0.36 mm, Minimum inhibitory concentration (MIC): 0.625 and 0.325 mg/ml, and ginger were ZI = 14.63 ± 0.30 mm and 11.56 ± 0.51mm, MIC: 9.0 mg/ml against E. coli and Salmonella sp., respectively. Two bands of garlic (Rf value = 0.31 and 0.50) and one band of ginger (Rf value = 0.71) showed inhibitory potential in TLC-Bioautography against both MDR isolates. Conclusion: Garlic and ginger were effective against MDR E. coli and Salmonella sp. These spices could be a suitable alternative during the antibiotic void.

A Case of Multidrug-Resistant (MDR) Tuberculosis and HIV Co-Infection.

Pulmonary tuberculosis (TB) infection is a public health concern in the United States. Mycobacterium tuberculosisantimicrobial resistance is a global public health concern. We present a case of a young man from Venezuela who presented to a hospital in New York and was newly diagnosed with pulmonary tuberculosis, human immunodeficiency virus (HIV), and syphilis. His TB isolate was found to be resistant to multiple anti-TB drugs, presenting unusual challenges in treating multidrug-resistant TB with HIV co-infection.

Environmental cleaning to prevent hospital-acquired infections on non-intensive care units: a pragmatic, single-centre, cluster randomized controlled, crossover trial comparing soap-based, disinfection and probiotic cleaning.

Background: The impact of environmental hygiene on the occurrence of hospital-acquired infections (HAIs) remains a subject of debate. We determined the effect of three different surface-cleaning strategies on the incidence of HAIs. Methods: Between June 2017 and August 2018 we conducted a pragmatic, cluster-randomized controlled crossover trial at 18 non-ICU wards in the university hospital of Berlin, Germany. Surfaces in patient rooms on the study wards were routinely cleaned using one of three agents: Soap-based (reference), disinfectant and probiotic. Each strategy was used on each ward for four consecutive months (4m-4m-4m). There was a one-month wash-in period at the beginning of the study and after each change in strategy. The order of strategies used was randomized for each ward. Primary outcome was the incidence of HAIs. The trial was registered with the German Clinical Trials Register, DRKS00012675. Findings: 13,896 admitted patients met the inclusion criteria, including 4708 in the soap-based (reference) arm, 4535 in the disinfectant arm and 4653 in the probiotic arm. In the reference group, the incidence density of HAIs was 2.31 per 1000 exposure days. The incidence density was similar in the disinfectant arm 2.21 cases per 1000 exposure days (IRR 0.95; 95% CI 0.69-1.31; p = 0.953) and the probiotic arm 2.21 cases per 1000 exposure days (IRR 0.96; 95% CI 0.69-1.32; p = 0.955). Interpretation: In non-ICU wards, routine surface disinfection proved not superior to soap-based or probiotic cleaning in terms of HAI prevention. Thus, probiotic cleaning could be an interesting alternative, especially in terms of environmental protection. Funding: Federal Ministry of Education and Research of Germany (03Z0818C). Bill and Melinda Gates Foundation (INV-004308).

Niclosamide as a Repurposing Drug against Corynebacterium striatum Multidrug-Resistant Infections.

Corynebacterium striatum (C. striatum) is an emerging multidrug-resistant (MDR) pathogen associated with nosocomial infections. In this scenario, we screened the antimicrobial activity of the anthelmintic drugs doramectin, moxidectin, selamectin and niclosamide against 20 C. striatum MDR clinical isolates. Among these, niclosamide was the best performing drug against C. striatum. Niclosamide cytotoxicity was evaluated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay on immortalized human keratinocyte cells (HaCaT). After 20 h of treatment, the recorded 50% cytotoxic concentration (CC50) was 2.56 µg/mL. The antibacterial efficacy was determined via disc diffusion, broth microdilution method and time-killing. Against C. striatum, niclosamide induced a growth inhibitory area of 22 mm and the minimum inhibitory concentration that inhibits 90% of bacteria (MIC90) was 0.39 µg/mL, exhibiting bactericidal action. The biofilm biomass eradicating action was investigated through crystal violet (CV), MTT and confocal laser scanning microscopy (CLSM). Niclosamide affected the biofilm viability in a dose-dependent manner and degraded biomass by 55 and 49% at 0.39 µg/mL and 0.19 µg/mL. CLSM images confirmed the biofilm biomass degradation, showing a drastic reduction in cell viability. This study could promote the drug-repurposing of the anthelmintic FDA-approved niclosamide as a therapeutic agent to counteract the C. striatum MDR infections.

Multidrug-Resistant Stenotrophomonas maltophilia Keratitis in a Penetrating Keratoplasty Patient.

We describe the management of a case of multidrug-resistant Stenotrophomonas maltophilia in a patient who had previously undergone photorefractive keratectomy and subsequent penetrating keratoplasty for Schnyder's crystalline corneal dystrophy. This pathogen is rare and, in this case, was multi-drug resistant.

In-vitro synergistic activity of colistin and meropenem against clinical isolates of carbapenem resistant E.coli and Klebsiella pneumoniae by checkerboard method.

CONTEXT: The emergence of drug resistant pathogens pose major threat to hospitalized patients as well as to the community associated with increased mortality and morbidity. The treatment of carbapenem resistant enterobacteriaceae, one of the top WHO priority pathogen remains a global issue. Combination therapy with different classes of antibiotics have been tried with the aim to reduce toxicity, to increase the efficacy of the drugs and to reduce resistance. The in-vitro synergy methods have to be carried out to determine whether the combination of those antibiotics are synergistic, antagonistic or additive. AIMS: We have performed in-vitro synergy testing by checkerboard method for colistin -meropenem combination to determine whether the combination of the two antibiotics were synergistic or antagonistic. METHODS AND MATERIAL: All the consecutive twenty five blood isolates of Escherichia coli and twenty five blood isolates of Klebsiella pneumoniae which were showing resistance to carbapenems by either disc diffusion or vitek 2 were collected over a period of 6 months and checkerboard method was performed. STATISTICAL ANALYSIS USED: The reduction of MIC of colisin on combination with meropenem compared to MIC of colistin alone is analyzed by McNemar's chisquare test with the help of software Stata version 14 and p value < 0.05 is considered as significant. RESULTS: 56% of K. pneumoniae showed synergy and 44% showed additive/indifference results. For E. coli 40% showed synergy and 60% showed additive/indifference. None of the isolates of E. coli and K. pneumoniae showed antagonism. There was more than two fold reduction in MIC of colistin (significant) on combining withmeropenem. CONCLUSIONS: The study results support the combination therapy to treat infections by multi-drug-resistant Klebsiela pneumoniae and Escherichia coli by in-vitro checkerboard testing method which inturn will be helpful for clinicians for judicious use of antimicrobials.

[Most important vaccinations in patients with rheumatological diseases and why]. / Wichtigste Impfungen bei Patienten mit rheumatologischen Erkrankungen und warum.

For a long time, most of the infectious diseases seemed to have become under control. In particular, vaccinations have contributed to this development. In recent years newly occurring bacterial infections caused by multidrug-resistant pathogens and viral infections, such as the chikungunya virus, influenza epidemics and currently the COVID-19 pandemic, are endangering the world population. This specifically affects patients with rheumatological diseases, who often require immunosuppressive therapy and are thus at risk for infections. Vaccinations can protect those affected, both individually and by generating herd immunity, and are thus an important instrument to reduce morbidity and mortality from infections. Knowledge of the indications and application of the individual vaccinations is particularly important for consistent implementation of the current recommendations.

Disseminated Corynebacterium jeikeium Infection in Cancer Patients.

Corynebacterium jeikeium is a multidrug-resistant gram-positive bacterium of the human skin flora and one of the most clinically important nondiphtherial corynebacteria in the acute care setting. C. jeikeium can cause different forms of infections, especially in immunocompromised patients with underlying risk factors and comorbidities. C. jeikeium was initially described in 1976 as a highly resistant coryneform bacteria causing severe sepsis in patients with hematologic malignancies and profound neutropenia. C. jeikeium infection has also been reported in the setting of endocarditis, septicemia, meningitis, pneumonia, and soft tissue infections. Management of disseminated C. jeikeium infection in immunocompromised cancer patients can be challenging due to its high virulence and rapid skin colonization. We present two cases of disseminated C. jeikeium infection in patients with acute myelogenous leukemia (AML) and underlying comorbidities. Both patients presented with neutropenic fever resistant to initial standard empiric antibiotic therapy.

Impact of antibiotic de-escalation on hospitalized patients with urinary tract infections: A retrospective cohort single center study.

BACKGROUND: Urinary tract infections (UTIs) can be caused by multiple drug-resistant bacteria. Empirical broad-spectrum antibiotics help minimize the risk of disease progression. Although antibiotic de-escalation is important to reduce resistance, adverse drug effects, and costs, few studies have evaluated the impact of antibiotic de-escalation on complicated UTIs in hospitalized patients. METHODS: In this retrospective cohort single center observational study conducted over a period of 1 year at Prince Sultan Military Medical City (PSMMC), the rate of antibiotic de-escalation following reporting culture and sensitivity results, hospital length of stay (LOS), and factors associated with antibiotic de-escalation failure were determined. RESULTS: Ninety-one patients were enrolled in this study. Baseline characteristics were comparable between groups. The rate of successful de-escalation was 29.7% (27 patients) while 70.3% (64 patients) failed to experience de-escalation. The median hospital LOS was significantly lower in successfully de-escalated patients, at 3 days interquartile range (IQR) (2-6), while in the failed group it was 10 days IQR (6-21) (p<0.001). However, the identified factor associated with failure was a multidrug-resistant (MDR) pathogen that was significantly higher in the failed group than in the successful group: 38 patients (59.4%) versus 6 patients (22.2%; p<0.001), respectively. CONCLUSION: Antibiotic de-escalation is an essential antimicrobial stewardship strategy. The findings of this study showed that de-escalation was associated with better patient outcomes (i.e., reduced hospital LOS) in patients admitted due to UTIs. In this study's site hospital, there is a potential for improving the current de-escalation rate. MDR pathogens were the only significant reason identified for de-escalation failure. Further data are needed on the large scale to evaluate reasons for de-escalation failure.

Clinical outcomes of urinary tract infection caused by extended spectrum beta-lactamase producing Enterobacteriaceae: a retrospective observational study comparing patients with and without systemic inflammatory response syndrome.

AIM: In severe urinary tract infection (UTI), susceptible antibiotics should be given. With the recent increase of multidrug-resistant bacteria, especially extended spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E), broad-spectrum antibiotics, such as carbapenems, are used more frequently, which could lead to a further increase of multidrug-resistant bacteria. We aimed to analyze the relationship between initial empirical antibiotic appropriateness and clinical outcomes in UTI, especially in patients with systemic inflammatory response syndrome (SIRS) and ESBL-E. METHODS: A retrospective observational study from 2012 to 2017. RESULTS: Among urine culture-positive cases with ≥105 colony-forming units/mL (n = 1,880), true UTI cases were extracted (n = 844) and divided into the SIRS group (n = 336 [ESBL-E12.8% (43/336)]) and non-SIRS group (n = 508 [ESBL-E12.6% (64/508)]). In the SIRS ESBL-E group, the initial antibiotics were susceptible in 55.8% (24/43), among which 91.7% (22/24) improved and 8.3% (2/24) deteriorated or died. The initial antibiotics were resistant in 44.2% (19/43), among which 47.4% (9/19) improved with the initial antibiotics, 47.4% (9/19) improved after escalating antibiotics, and 5.3% (1/19) deteriorated or died. In the SIRS group, 14 cases had true bacteremia with ESBL-E. Seven cases were initiated with inappropriate antibiotics; four cases showed improvement before or without antibiotic change and three cases improved after antibiotic escalation. CONCLUSION: Initiation of narrow-spectrum antibiotics in septic UTI with ESBL-E might not deteriorate the clinical outcome if promptly escalated on clinical deterioration or with ESBL-E culture results. Further investigation is warranted to guide judicious use of initial antibiotics.

Temporal evolution of Acinetobacter baumannii ST107 clone: conversion of blaOXA-143 into blaOXA-231 coupled with mobilization of ISAba1 upstream occAB1.

Nine carbapenem-resistant Acinetobacter baumannii isolates carrying blaOXA-231 and an ISAba1 upstream occAB1 were evaluated. They were clonally related and belonged to ST107. An OXA-143-producing A. baumannii ST107 strain (Ac-148) that did not possess ISAba1 upstream occAB1 was included in the analysis. Reduction in the expression of occAB1 and a 4-fold increase of carbapenem MICs were observed for all isolates, except for the Ac-148 strain, probably due to the presence of ISAba1 upstream occAB1 but in the same transcriptional orientation. We reported an A. baumannii ST107 clone carrying blaOXA-143 that acquired a mutation resulting into blaOXA-231 and mobilized ISAba1 upstream occAB1.

Molecular Mechanism of Quorum-Sensing in Enterococcus faecalis: Its Role in Virulence and Therapeutic Approaches.

Quorum-sensing systems control major virulence determinants in Enterococcusfaecalis, which causes nosocomial infections. The E. faecalis quorum-sensing systems include several virulence factors that are regulated by the cytolysin operon, which encodes the cytolysin toxin. In addition, the E. faecalis Fsr regulator system controls the expression of gelatinase, serine protease, and enterocin O16. The cytolysin and Fsr virulence factor systems are linked to enterococcal diseases that affect the health of humans and other host models. Therefore, there is substantial interest in understanding and targeting these regulatory pathways to develop novel therapies for enterococcal infection control. Quorum-sensing inhibitors could be potential therapeutic agents for attenuating the pathogenic effects of E. faecalis. Here, we discuss the regulation of cytolysin, the LuxS system, and the Fsr system, their role in E. faecalis-mediated infections, and possible therapeutic approaches to prevent E. faecalis infection.