Search

In severe Coronavirus disease 2019 (COVID-19), bloodstream infections (BSIs) are an increasing cause of morbidity and mortality. In critically ill patients with COVID-19, we aimed to evaluate the prevalence, clinical profiles, and outcomes of BSIs. This single-center prospective investigation was conducted at a tertiary care hospital in Western India. All patients (>18 years of age) hospitalized in the intensive care unit (ICU) or ward with RT-PCR-confirmed COVID-19 were included. Demographic information, clinical proficiency, and antibiotic resistance patterns were assessed. Of the 550 patients admitted to the COVID ICU, subsequent BSIs occurred in 7.45% of patients. Gram-negative pathogens comprised a significant proportion of BSIs (53/73, 72.6%). The most frequent isolates were Klebsiella pneumoniae (22/73, 30.1%), Acinetobacter baumannii (11/73,15.06%), and Escherichia coli (7/23, 9.58%). In 57.8% of the cases, multidrug-resistant organisms (MDRO) were discovered. The Enterococcus and K. pneumoniae families comprise the majority of MDRO. Gram-negative bacteria (30.18% [16/53]) were resistant to carbapenems. Increased total leukocyte count, mechanical ventilation, and the presence of comorbidities were significantly associated with the incidence of BSIs. In COVID-19-linked BSIs, we discovered a high frequency of A. baumannii. Clinicians should be aware of potential BSIs in the presence of comorbidities, elevated leukocyte count, and mechanical ventilation. To improve the results, empirical antibiotics must be started promptly, and the situation must be de-escalated quickly. The most frequent isolates were A. baumannii and K. pneumoniae ([11/73, 15.06%] and [22/73, 30.1%], respectively). To reduce the incidence of MDRO, infection control procedures should be strictly followed in patients with multidrug resistance.

Carbapenem-resistant Acinetobacter baumannii complex (CRAB) poses a significant global health challenge owing to its resistance to multiple antibiotics and limited treatment options. Polymyxin-based therapies have been widely used to treat CRAB infections; however, they are associated with high mortality rates and common adverse events such as nephrotoxicity. Recent developments include numerous observational studies and randomized clinical trials investigating antibiotic combinations, repurposing existing antibiotics, and the development of novel agents. Consequently, recommendations for treating CRAB are undergoing significant changes. The importance of colistin is decreasing, and the role of sulbactam, which exhibits direct antibacterial activity against A. baumannii complex, is being reassessed. High-dose ampicillin-sulbactam-based combination therapies, as well as combinations of sulbactam and durlobactam, which prevent the hydrolysis of sulbactam and binds to penicillin-binding protein 2, have shown promising results. This review introduces recent advancements in CRAB infection treatment based on clinical trial data, highlighting the need for optimized treatment protocols and comprehensive clinical trials to combat the evolving threat of CRAB effectively. [ABSTRACT FROM AUTHOR]

In severe Coronavirus disease 2019 (COVID-19), bloodstream infections (BSIs) are an increasing cause of morbidity and mortality. In critically ill patients with COVID-19, we aimed to evaluate the prevalence, clinical profiles, and outcomes of BSIs. This single-center prospective investigation was conducted at a tertiary care hospital in Western India. All patients (>18 years of age) hospitalized in the intensive care unit (ICU) or ward with RT-PCR-confirmed COVID-19 were included. Demographic information, clinical proficiency, and antibiotic resistance patterns were assessed. Of the 550 patients admitted to the COVID ICU, subsequent BSIs occurred in 7.45% of patients. Gram-negative pathogens comprised a significant proportion of BSIs (53/73, 72.6%). The most frequent isolates were Klebsiella pneumoniae (22/73, 30.1%), Acinetobacter baumannii (11/73,15.06%), and Escherichia coli (7/23, 9.58%). In 57.8% of the cases, multidrug-resistant organisms (MDRO) were discovered. The Enterococcus and K. pneumoniae families comprise the majority of MDRO. Gram-negative bacteria (30.18% [16/53]) were resistant to carbapenems. Increased total leukocyte count, mechanical ventilation, and the presence of comorbidities were significantly associated with the incidence of BSIs. In COVID-19-linked BSIs, we discovered a high frequency of A. baumannii. Clinicians should be aware of potential BSIs in the presence of comorbidities, elevated leukocyte count, and mechanical ventilation. To improve the results, empirical antibiotics must be started promptly, and the situation must be de-escalated quickly. The most frequent isolates were A. baumannii and K. pneumoniae ([11/73, 15.06%] and [22/73, 30.1%], respectively). To reduce the incidence of MDRO, infection control procedures should be strictly followed in patients with multidrug resistance. [ABSTRACT FROM AUTHOR]

Summary: Antimicrobial resistance remains a persistent and pressing public health concern. Here, we describe the synthesis of original triazole-containing inhibitors targeting the DNA gyrase, a well-validated drug target for developing new antibiotics. Our compounds demonstrate potent antibacterial activity against various pathogenic bacteria, with notable potency against Mycobacterium tuberculosis (Mtb). Moreover, one hit, compound 10a, named BDM71403, was shown to be more potent in Mtb than the NBTI of reference, gepotidacin. Mechanistic enzymology assays reveal a competitive interaction of BDM71403 with fluoroquinolones within the Mtb gyrase cleavage core. High-resolution cryo-electron microscopy structural analysis provides detailed insights into the ternary complex formed by the Mtb gyrase, double-stranded DNA, and either BDM71403 or gepotidacin, providing a rational framework to understand the superior in vitro efficacy on Mtb. This study highlights the potential of triazole-based scaffolds as promising gyrase inhibitors, offering new avenues for drug development in the fight against antimicrobial resistance.

Abstract Background The COVID-19 pandemic has increased the incidence of ventilator-associated pneumonia (VAP) among critically ill patients. However, a comparison of VAP incidence in COVID-19 and non-COVID-19 cohorts, particularly in a context with a high prevalence of multidrug-resistant (MDR) organisms, is lacking. Material and Methods We conducted a single-center, mixed prospective and retrospective cohort study comparing COVID-19 patients admitted to the intensive care unit (ICU) of the “Città della Salute e della Scienza” University Hospital in Turin, Italy, between March 2020 and December 2021 (COVID-19 group), with a historical cohort of ICU patients admitted between June 2016 and March 2018 (NON-COVID-19 group). The primary objective was to define the incidence of VAP in both cohorts. Secondary objectives were to evaluate the microbial cause, resistance patters, risk factors and impact on 28 days, ICU and in-hospital mortality, duration of ICU stay, and duration of hospitalization). Results We found a significantly higher incidence of VAP (51.9% - n = 125) among the 241 COVID-19 patients compared to that observed (31.2% - n = 78) among the 252 NON-COVID-19 patients. The median SOFA score was significantly lower in the COVID-19 group (9, Interquartile range, IQR: 7–11 vs. 10, IQR: 8–13, p

Background: The COVID-19 pandemic has increased the incidence of ventilator-associated pneumonia (VAP) among critically ill patients. However, a comparison of VAP incidence in COVID-19 and non-COVID-19 cohorts, particularly in a context with a high prevalence of multidrug-resistant (MDR) organisms, is lacking. Material and Methods: We conducted a single-center, mixed prospective and retrospective cohort study comparing COVID-19 patients admitted to the intensive care unit (ICU) of the "Città della Salute e della Scienza" University Hospital in Turin, Italy, between March 2020 and December 2021 (COVID-19 group), with a historical cohort of ICU patients admitted between June 2016 and March 2018 (NON-COVID-19 group). The primary objective was to define the incidence of VAP in both cohorts. Secondary objectives were to evaluate the microbial cause, resistance patters, risk factors and impact on 28 days, ICU and in-hospital mortality, duration of ICU stay, and duration of hospitalization). Results: We found a significantly higher incidence of VAP (51.9% - n = 125) among the 241 COVID-19 patients compared to that observed (31.2% - n = 78) among the 252 NON-COVID-19 patients. The median SOFA score was significantly lower in the COVID-19 group (9, Interquartile range, IQR: 7–11 vs. 10, IQR: 8–13, p < 0.001). The COVID-19 group had a higher prevalence of Gram-positive bacteria-related VAP (30% vs. 9%, p < 0.001), but no significant difference was observed in the prevalence of difficult-to-treat (DTR) or MDR bacteria. ICU and in-hospital mortality in the COVID-19 and NON-COVID-19 groups were 71% and 74%, vs. 33% and 43%, respectively. The presence of COVID-19 was significantly associated with an increased risk of 28-day all-cause hospital mortality (Hazard ratio, HR: 7.95, 95% Confidence Intervals, 95% CI: 3.10-20.36, p < 0.001). Tracheostomy and a shorter duration of mechanical ventilation were protective against 28-day mortality, while dialysis and a high SOFA score were associated with a higher risk of 28-day mortality. Conclusion: COVID-19 patients with VAP appear to have a significantly higher ICU and in-hospital mortality risk regardless of the presence of MDR and DTR pathogens. Tracheostomy and a shorter duration of mechanical ventilation appear to be associated with better outcomes. [ABSTRACT FROM AUTHOR]

Abstract Background The systematic collection of valid data related to hospital-acquired infections (HAIs) is considered effective for nosocomial infection prevention and control programs. New strategies to reduce HAIs have recently fueled the adoption of real-time automatic nosocomial infection surveillance systems (RT-NISSs). Although RT-NISSs have been implemented in some hospitals for several years, the effect of RT-NISS on HAI prevention and control needs to be further explored. Methods A retrospective, descriptive analysis of inpatients from January 2017 to December 2019 was performed. We collected hospital-acquired infection (HAI) cases and multidrug resistant organism (MDRO) infection cases by traditional surveillance in period 1 (from January 2017 to December 2017), and these cases were collected in period 2 (from January 2018 to December 2018) and period 3 (from January 2019 to December 2019) using a real-time nosocomial infection surveillance system (RT-NISS). The accuracy of MDRO infection surveillance results over the 3 periods was examined. The trends of antibiotic utilization rates and pathogen culture rates in periods 2 and 3 were also analysed. Results A total of 114,647 inpatients, including 2242 HAI cases, were analysed. The incidence of HAIs in period 2 was significantly greater than that in period 1 (2.28% vs. 1.48%, χ2 = 61.963, p

Acinetobacter infection with multidrug resistant strains is an emerging infection of global concern as it leads to serious disease. They are also important pathogens causing hospital acquired infections. Information on the prevalence, spectrum of illness and antibiotic sensitivity pattern of Acinetobacter is important for appropriate management of patients. We aimed to determine the prevalence of Acinetobacter species and evaluate the clinical profile and antibiotic sensitivity pattern of Acinetobacter species from various clinical samples. From October 2018 to September 2019, various clinical samples received in the microbiology laboratory were studied from the electronic records and the data on the isolation of Acinetobacter from these samples and its antibiotic sensitivity pattern was collected and analysed. The clinical data was also collected to determine the clinical spectrum. The prevalence of Acinetobacter species from various clinical samples was found to be 8.9%. Isolates were more common in general wards than in ICUs. The Acinetobacter infections occurred significantly in male patients (65.7%) than in female patients (34.3%), with male: female ratio of 1.9:1. The most common infection caused by Acinetobacter species was Wound infection (54.36%) followed by Respiratory tract infection (34.27%). Multidrug resistance was seen in 75 % of the isolates. Significant prevalence of multidrug resistant Acinetobacter infections was noted in our study. The findings emphasize the need for strict hospital infection control practices and the restricted use of antibiotics to prevent the occurrence of these infections.

Abstract Discontinuation of antimicrobial stewardship programs (ASPs) and increased antibiotic use were described during SARS-CoV-2 pandemic. In order to measure COVID-19 impact on ASPs in a setting of high multidrug resistance organisms (MDRO) prevalence, a qualitative survey was designed. In July 2021, eighteen ID Units were asked to answer a questionnaire about their hospital characteristics, ASPs implementation status before the pandemic and impact of SARS-CoV-2 pandemic on ASPs after the 1st and 2nd pandemic waves in Italy. Nine ID centres (50%) reported a reduction of ASPs and in 7 cases (38.9%) these were suspended. After the early pandemic waves, the proportion of centres that restarted their ASPs was higher among the ID centres where antimicrobial stewardship was formally identified as a priority objective (9/11, 82%, vs 2/7, 28%). SARS-CoV-2 pandemic had a severe impact in ASPs in a region highly affected by COVID-19 and antimicrobial resistance but weaknesses related to the pre-existent ASPs might have played a role.

Summary: The emergence and spread of artemisinin-tolerant malaria parasites threatens malaria control programmes worldwide. Mutations in the propeller domain of the Kelch13 protein confer Plasmodium falciparum artemisinin resistance (ART-R). ART-R is linked to the reduced susceptibility of temporary growth-arrested ring-stage parasites, but the metabolic mechanisms remain elusive. We generated two PfKelch13 mutant lines via CRISPR-Cas9 gene editing which displayed a reduced susceptibility accompanied by an extended ring stage. The metabolome of ART-induced ring-stage growth arrest parasites carrying PfKelch13 mutations showed significant alterations in the tricarboxylic acid (TCA) cycle, glycolysis, and amino acids metabolism, pointing to altered energy and porphyrin metabolism with metabolic plasticity. The critical role of these pathways was further confirmed by altering metabolic flow or through chemical inhibition. Our findings uncover that the growth arrestment associated with ART-R is potentially attributed to the adaptative metabolic plasticity, indicating that the defined metabolic remodeling turns out to be the trigger for ART-R.

Background: The systematic collection of valid data related to hospital-acquired infections (HAIs) is considered effective for nosocomial infection prevention and control programs. New strategies to reduce HAIs have recently fueled the adoption of real-time automatic nosocomial infection surveillance systems (RT-NISSs). Although RT-NISSs have been implemented in some hospitals for several years, the effect of RT-NISS on HAI prevention and control needs to be further explored.Methods: A retrospective, descriptive analysis of inpatients from January 2017 to December 2019 was performed. We collected hospital-acquired infection (HAI) cases and multidrug resistant organism (MDRO) infection cases by traditional surveillance in period 1 (from January 2017 to December 2017), and these cases were collected in period 2 (from January 2018 to December 2018) and period 3 (from January 2019 to December 2019) using a real-time nosocomial infection surveillance system (RT-NISS). The accuracy of MDRO infection surveillance results over the 3 periods was examined. The trends of antibiotic utilization rates and pathogen culture rates in periods 2 and 3 were also analysed.Results: A total of 114,647 inpatients, including 2242 HAI cases, were analysed. The incidence of HAIs in period 2 was significantly greater than that in period 1 (2.28% vs. 1.48%, χ2 = 61.963, p < 0.001) and period 3 (2.28% vs. 2.05%, χ2 = 4.767, p = 0.029). The incidence of five HAI sites, including respiratory infection, urinary tract infection (UTI), surgical site infection (SSI), bloodstream infection (BSI) and skin and soft tissue infection, was significantly greater in period 2 compared with period 1 (both p < 0.05) but was not significantly different from that in period 3. The incidence of hospital-acquired MDRO infections in period 3 was lower than that in period 2. The identification of MDRO infection cases using the RT-NISS achieved a high level of sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV), especially in period 3 (Se = 100%, Sp = 100%, PPV = 100% and NPV = 100%).Conclusion: The adoption of a RT-NISS to adequately and accurately collect HAI cases is useful to prevent and control HAIs. Furthermore, RT-NISSs improve accuracy in MDRO infection case reporting, which can timely and accurately guide and supervise clinicians in implementing MDRO infection prevention and control measures. [ABSTRACT FROM AUTHOR]

Background: Indiscriminate use of colistin for gram-negative infections has led to increase incidence of colistin resistance. The problem of nosocomial infections especially caused by multi-drug-resistant gram-negative bacteria (MDR-GNB), particularly Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae is a matter of great concern. This study was conducted to find out the prevalence of colistin resistant gram-negative isolates from patients attending outdoor patient department (OPD), those admitted in wards and Intensive care unit from a Tertiary care centre in North-East India. Materials and Methods: Clinical samples obtained were processed using standard microbiological methods. The gram-negative isolates showing colistin resistance by Kirby-Bauer's disc diffusion method were included and further subjected for MIC (minimum inhibitory concentration) testing by VITEK-2 system followed by confirmation by Broth microdilution method. Results: Colistin resistance was observed in 26 isolates out of 1040 gram-negative isolates using Broth microdilution method. The MIC values varied from 8 to = 32 μg/ml. Majority of them belong to Pseudomonas species followed by Acinetobacter species and were highly resistant to ß-lactams, aminoglycosides, fluoroquinolones. Conclusion: This study highlights an increasing trend of colistin resistance amongst multidrug resistant (MDR) gram-negative isolates warranting routine screening for colistin resistance to guide appropriate therapy for future use. [ABSTRACT FROM AUTHOR]

Multidrug-resistant organisms are an increasing concern in patients with decompensated cirrhosis. We aimed to evaluate the prevalence of infections with carbapenem-resistant Enterobacteriaceae in patients with decompensated cirrhosis. Patients with decompensated cirrhosis admitted to ICU were included. The isolated Enterobacteriaceae strains were tested for carbapenemase-producing genes using the Roche LightMix® Modular VIM/IMP/NDM/GES/KPC/OXA48 -carbapenemase detection kit. 48 culture-positive infections were registered in 75 patients with acutely decompensated cirrhosis. Thirty patients contracted a second infection. 46% of bacteria isolated at admission and 60% of bacteria responsible for infections identified during ICU-stay were multiresistant. ESBL+ Enterobacteriaceae were predominant at admission, while carbapenem-resistance was dominant in both Enterobacteriaceae and Non-Fermenting-Gram-Negative Bacteria responsible for infections diagnosed during hospitalisation. OXA 48 or KPC type carbapenemases were present in 30% of the analyzed Enterobacteriaceae and in 40% of the phenotypically carbapenem-resistant Klebsiella pneumoniae strains. The length of ICU stay was a risk-factor for a second infection (p=0.04). Previous carbapenem usage was associated with occurence of infections with carbapenem-resistant Gram-negative bacteria during hospitalization (p=0.03). The prevalence of infections with carbapenem-resistant Enterobacteriaceae is high in patients with decompensated cirrhosis admitted to ICU. Carbapenemase-producing genes in Enterobacteriaceae in our center are bla OXA-48 and bla KPC. [ABSTRACT FROM AUTHOR]

Acinetobacter infection with multidrug resistant strains is an emerging infection of global concern as it leads to serious disease. They are also important pathogens causing hospital acquired infections. Information on the prevalence, spectrum of illness and antibiotic sensitivity pattern of Acinetobacter is important for appropriate management of patients. We aimed to determine the prevalence of Acinetobacter species and evaluate the clinical profile and antibiotic sensitivity pattern of Acinetobacter species from various clinical samples. From October 2018 to September 2019, various clinical samples received in the microbiology laboratory were studied from the electronic records and the data on the isolation of Acinetobacter from these samples and its antibiotic sensitivity pattern was collected and analysed. The clinical data was also collected to determine the clinical spectrum. The prevalence of Acinetobacter species from various clinical samples was found to be 8.9%. Isolates were more common in general wards than in ICUs. The Acinetobacter infections occurred significantly in male patients (65.7%) than in female patients (34.3%), with male: female ratio of 1.9:1. The most common infection caused by Acinetobacter species was Wound infection (54.36%) followed by Respiratory tract infection (34.27%). Multidrug resistance was seen in 75 % of the isolates. Significant prevalence of multidrug resistant Acinetobacter infections was noted in our study. The findings emphasize the need for strict hospital infection control practices and the restricted use of antibiotics to prevent the occurrence of these infections. [ABSTRACT FROM AUTHOR]

Antibiotic use drives antibiotic resistance. To systematically review the literature and estimate associations between prior exposure to antibiotics across World Health Organization's (WHO) AWaRe categories (Access, Watch, Reserve) and isolation of critical and high-priority multidrug resistant organisms (MDROs) on the WHO priority pathogen list. Embase, Ovid Medline, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov (from inception to 20/08/2020). Case-control, cohort, or experimental studies that assessed the risk of infection/colonization with MDROs. Inpatients or outpatients of any age and sex. Prior exposure to antibiotics that could be categorized into the AWaRe framework. Tailored design-specific checklists applied to each included study. For each antibiotic/class, crude odds ratios (ORs) were pooled through random-effects meta-analyses, both overall and by MDRO. Heterogeneity was examined. We identified 349 eligible studies. All were observational, prone to bias due to design and lack of adjustment for confounding, and not primarily designed to compare associations across AWaRe categories. We found statistically significant associations between prior exposure to almost all antibiotics/classes across AWaRe categories and colonization/infection with any MDRO. We observed higher ORs for Watch and Reserve antibiotics than with Access antibiotics. First generation cephalosporins (Access) had the least association with any MDRO colonization/infection (58 studies; OR = 1.2 [95% CI: 1.0–1.4]), whereas strongest associations were estimated for linezolid (Reserve) (22 studies; OR = 2.6 [95% CI: 2.1–3.1]), followed by carbapenems (Watch) (237 studies; OR = 2.3 [95% CI: 2.1–2.5]). There was high heterogeneity for all antibiotic/MDRO associations. Optimising use of Access antibiotics is likely to reduce the selection of MDROs and global antibiotic resistance. Despite data limitations, our study offers a strong rationale for further adoption of AWaRe as an important tool to improve antibiotic use globally. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance remains a persistent and pressing public health concern. Here, we describe the synthesis of original triazole-containing inhibitors targeting the DNA gyrase, a well-validated drug target for developing new antibiotics. Our compounds demonstrate potent antibacterial activity against various pathogenic bacteria, with notable potency against Mycobacterium tuberculosis ( Mtb ). Moreover, one hit, compound 10a , named BDM71403, was shown to be more potent in Mtb than the NBTI of reference, gepotidacin. Mechanistic enzymology assays reveal a competitive interaction of BDM71403 with fluoroquinolones within the Mtb gyrase cleavage core. High-resolution cryo-electron microscopy structural analysis provides detailed insights into the ternary complex formed by the Mtb gyrase, double-stranded DNA, and either BDM71403 or gepotidacin, providing a rational framework to understand the superior in vitro efficacy on Mtb . This study highlights the potential of triazole-based scaffolds as promising gyrase inhibitors, offering new avenues for drug development in the fight against antimicrobial resistance., Competing Interests: The authors declare no competing financial interests., (© 2024 The Author(s).)

Discontinuation of antimicrobial stewardship programs (ASPs) and increased antibiotic use were described during SARS-CoV-2 pandemic. In order to measure COVID-19 impact on ASPs in a setting of high multidrug resistance organisms (MDRO) prevalence, a qualitative survey was designed. In July 2021, eighteen ID Units were asked to answer a questionnaire about their hospital characteristics, ASPs implementation status before the pandemic and impact of SARS-CoV-2 pandemic on ASPs after the 1st and 2nd pandemic waves in Italy. Nine ID centres (50%) reported a reduction of ASPs and in 7 cases (38.9%) these were suspended. After the early pandemic waves, the proportion of centres that restarted their ASPs was higher among the ID centres where antimicrobial stewardship was formally identified as a priority objective (9/11, 82%, vs 2/7, 28%). SARS-CoV-2 pandemic had a severe impact in ASPs in a region highly affected by COVID-19 and antimicrobial resistance but weaknesses related to the pre-existent ASPs might have played a role. [ABSTRACT FROM AUTHOR]

Introduction: Secondary infections are emerging as a serious threat among hospitalised patients of Coronavirus Disease-2019 (COVID-19). Overuse of antibiotics and inadequate infection control practices due to COVID-19 patients' workload leads to a sudden upsurge of Multidrug Resistance (MDR) pathogens in healthcare settings attributing to higher mortality rates among the same. Aim: To detect the secondary infection rate among COVID-19 patients admitted to the hospital ward and Intensive Care Unit (ICU), and report the impact on antimicrobial resistance and patient outcome. Materials and Methods: A retrospective study was conducted for a period of three months of the second COVID-19 wave from 15th April 2021 to 14th july 2021 in the Department of Microbiology, Himalayan Institute of Medical Sciences (HIMS), Swami Rama Himalayan University (SRHU), Dehradun, Uttarakhand, India. All clinical samples of Reverse Transcriptase Polymerase Chain Reaction (RTPCR) positive cases of COVID-19 received in the laboratory were cultured and identified using the Vitek-2 automated system and conventional fungal culture. Relevant demographic, characteristics, and clinical outcome data were obtained from records of the patient and recorded in reporting forms and were analysed for the study. Results were analysed with Statistical Package for the Social Sciences (SPSS) version 20.0 and Microsoft Excel 2019. Results: Overall secondary infection rate of 135 (13.6%) was found among COVID-19 admitted patients. The most commonly isolated bacterial pathogens were Coagulase-negative Staphylococcus species (18.52%) and Enterococcus species (8.89%). Whereas the most common fungal isolates were Candida species (20.75%) and Rhizopus (8.15%). In the present study, 60.5% of bacterial pathogens isolated were Multidrug-resistant Organisms (MDRO). Mortality among COVID-19 patients with secondary infection was reported as 53% which was higher than the overall mortality rate of 36% in the same. Conclusion: A high secondary infection rate, MDRO isolation rate, and high mortality among COVID-19 with secondary infection were reported. This shows the urgent need for reinforcement of infection control practices and strict antimicrobial stewardship policies. [ABSTRACT FROM AUTHOR]

Background: Bloodstream infections (BSI) caused by highly resistant pathogens in non-ICU COVID-19 departments pose important challenges. Methods: We performed a comparative analysis of incidence and microbial epidemiology of BSI in COVID-19 vs. non-COVID-19, non-ICU departments between 1 September 2020-31 October 2021. Risk factors for BSI and its impact on outcome were evaluated by a case-control study which included COVID-19 patients with/without BSI. Results: Forty out of 1985 COVID-19 patients developed BSI. The mean monthly incidence/100 admissions was 2.015 in COVID-19 and 1.742 in non-COVID-19 departments. Enterococcus and Candida isolates predominated in the COVID-19 group (p < 0.001 and p = 0.018, respectively). All Acinetobacter baumannii isolates were carbapenem-resistant (CR). In the COVID-19 group, 33.3% of Klebsiella pneumoniae was CR, 50% of Escherichia coli produced ESBL and 19% of Enterococcus spp. were VRE vs. 74.5%, 26.1% and 8.8% in the non-COVID-19 group, respectively. BSI was associated with prior hospitalization (p = 0.003), >2 comorbidities (p < 0.001), central venous catheter (p = 0.015), severe SARS-CoV-2 pneumonia and lack of COVID-19 vaccination (p < 0.001). In the multivariate regression model also including age and multiple comorbidities, only BSI was significantly associated with adverse in-hospital outcome [OR (CI95%): 21.47 (3.86–119.21), p < 0.001]. Conclusions: BSI complicates unvaccinated patients with severe SARS-CoV-2 pneumonia and increases mortality. BSI pathogens and resistance profiles differ among COVID-19/non-COVID-19 departments, suggesting various routes of pathogen acquisition. [ABSTRACT FROM AUTHOR]

The emergence of carbapenem-resistant Enterobacteriaceae (CRE) is an important public health issue worldwide, not only due to the potential of these pathogens for widespread dissemination, but also due to the limited antimicrobial therapy options, and the elevated mortality rates associated with these infections. As with other multidrug-resistant organisms (MDROs), active surveillance via timely testing, early diagnosis, and contact isolation is an important strategy to control the occurrence and spread of CRE bacteria. Here we summarize the epidemiology of CRE infections in Japan from 2015 to 2019. Data were extracted from a public dataset collected by the nationwide surveillance system via the National Institute of Infectious Diseases (NIID) of Japan. The annual number of reported CRE infections has remained relatively stable, with a tendency to increase in the last two years (1671 cases reported in 2015 and 2333 cases reported in 2019). The majority of patients who presented CRE infections over this five year period were older than 65 years (~80%, mean age 75), 60% of them were men, and mortality rates were around 3.5%. Importantly, about 60% of infections are caused by both Enterobacter cloacae and Klebsiella aerogenes (previously known as Enterobacter aerogenes), the former being the most common pathogen in 2015 and 2016 (~30%), and the latter the leading pathogen since 2017 (~40%). The most common carbapenemase isolated was the IMP carbapenemase type. Further studies are needed to determine the prevalence of CRE colonization, especially in the healthcare setting, and to elucidate the mechanisms behind the local predominance of Klebsiella aerogenes and Enterobacter cloacae. [ABSTRACT FROM AUTHOR]

In spite of the widespread implementation of preventive strategies, the prevalence of healthcare-associated infections (HAIs) remains high. The prevalence of multidrug resistant organisms is high in HAIs. In 2019, the World Health Organization retained antimicrobial resistance as one of the ten issues for global health. The development of vaccines may contribute to the fight against antimicrobial resistance to reduce the burden of HAIs. Staphylococcus aureus, Gram negative bacteria and Clostridium difficile are the most frequent pathogens reported in HAIs. Consequently, the development of vaccines against these pathogens is crucial. At this stage, the goal of obtaining effective vaccines against S.aureus and Gram negative bacteria has not yet been achieved. However, we can expect in the near future availability of a vaccine against C. difficile. In addition, identifying populations who may benefit from these vaccines is complex, as at-risk patients are not great responders to vaccines, or as vaccination may occur too late, when they are already confronted to the risk. Vaccinating healthcare workers (HCWs) against these pathogens may have an impact only if HCWs play a role in the transmission and in the pathogens acquisition in patients, if the vaccine is effective to reduce pathogens carriage and if vaccine coverage is sufficient to protect patients. Acceptance of these potential vaccines should be evaluated and addressed in patients and in HCWs.

Introduction: Secondary infections (SIs) are emerging as a serious threat among hospitalised patients of Coronavirus Disease-2019 (COVID-19). Overuse of antibiotics and inadequate infection control practices due to COVID-19 patients’ workload leads to a sudden upsurge of Multidrug Resistance (MDR) pathogens in healthcare settings attributing to higher mortality rates among the same. Aim: To detect the secondary infection rate among COVID-19 patients admitted to the hospital ward and Intensive Care Unit (ICU), and report the impact on antimicrobial resistance and patient outcome. Materials and Methods: A retrospective study was conducted for a period of three months of the second COVID-19 wave from 15th April 2021 to 14th July 2021 in the Department of Microbiology, Himalayan Institute of Medical Sciences (HIMS), Swami Rama Himalayan University (SRHU), Dehradun, Uttarakhand, India. All clinical samples (N=992) of Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) positive cases of COVID-19 received in the laboratory were cultured and identified using the Vitek-2 automated system and conventional fungal culture. Relevant demographic, characteristics, and clinical outcome data were obtained from records of the patient and recorded in reporting forms and were analysed for the study. Results were analysed with Statistical Package for the Social Sciences (SPSS) version 20.0 and Microsoft Excel 2019. Results: Overall secondary infection rate of 135 (13.6%) was found among COVID-19 admitted patients. The most commonly isolated bacterial pathogens were Coagulase-negative Staphylococcus species (18.52%) and Enterococcus species (8.89%). Whereas the most common fungal isolates were Candida species (20.75%) and Rhizopus (8.15%). In the present study, 60.5% of bacterial pathogens isolated were Multidrug-resistant Organisms (MDRO). Mortality among COVID-19 patients with secondary infection was reported as 53% which was higher than the overall mortality rate of 36% in the same. Conclusion: A high secondary infection rate, MDRO isolation rate, and high mortality among COVID-19 with secondary infection were reported. This shows the urgent need for reinforcement of infection control practices and strict antimicrobial stewardship policies.

Background: Systemic colistin is often utilized for management of drug resistant lower respiratory tract infections (LRTI). Nebulized administration of colistin allows direct instillation of active agent to maximize concentrations and limit systemic toxicities. Current literature supports efficacy of nebulized colistin as adjunctive treatment for LRTI. However, there is a paucity of data surrounding safety of this administration technique. Methods: The electronic medical record (EMR) was queried to identify patients treated with nebulized colistin between January 1, 2016 and December 31, 2018. The data collected from the EMR and hospital adverse drug reaction (ADR) reporting systems included: demographics, dose, serum creatinine (SCr), concomitant nephrotoxins, infecting pathogen, treatment-emergent ADRs, and drug toxicities. The primary outcome was prevalence of renal, neurologic, or respiratory ADRs secondary to nebulized colistin. Results: Thirty-two patients were administered nebulized colistin during the study period. Approximately 19% of patients had baseline chronic kidney disease. Cultures were positive in 29 patients of which 11 organisms were resistant to all tested antimicrobials. Three patients experienced acute kidney injury (AKI), 1 patient experienced a neurologic reaction, and 1 patient experienced a respiratory reaction, though none were considered treatment-related. Conclusion: The results of our study signify localized administration of colistin results in a low incidence of systemic adverse events. Nebulized colistin is a safe adjunct for managing LRTI. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Acinetobacter baumannii complex (CRAB) poses a significant global health challenge owing to its resistance to multiple antibiotics and limited treatment options. Polymyxin-based therapies have been widely used to treat CRAB infections; however, they are associated with high mortality rates and common adverse events such as nephrotoxicity. Recent developments include numerous observational studies and randomized clinical trials investigating antibiotic combinations, repurposing existing antibiotics, and the development of novel agents. Consequently, recommendations for treating CRAB are undergoing significant changes. The importance of colistin is decreasing, and the role of sulbactam, which exhibits direct antibacterial activity against A. baumannii complex, is being reassessed. High-dose ampicillin-sulbactam-based combination therapies, as well as combinations of sulbactam and durlobactam, which prevent the hydrolysis of sulbactam and binds to penicillin-binding protein 2, have shown promising results. This review introduces recent advancements in CRAB infection treatment based on clinical trial data, highlighting the need for optimized treatment protocols and comprehensive clinical trials to combat the evolving threat of CRAB effectively., Competing Interests: No conflict of interest., (© 2024 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, The Korean Society for AIDS, and Korean Society of Pediatric Infectious Diseases.)

Introduction: Diabetic Foot Ulcers (DFU) represent a silent epidemic and are the leading cause of 80% of non traumatic lower-limb amputations. Anaemia in diabetes may have adverse effects on systemic diseases and predict the progression of diabetes complications. Biofilms act as a mechanical barrier to antimicrobials and immune system cells and contribute to Multidrug Resistance (MDR). Aim: To determine the bacteriome and mycobiome of diabetic ulcers and the associated biofilm formation and anti-microbial resistance profile of the pathogens. Also, to determine the molecular characterisation of biofilm-forming resistant isolates by Polymerase Chain Reaction (PCR). Materials and Methods: This cross-sectional study was done on 150 diabetic patients with non healing ulcers and was chosen and studied from January-December 2019. Pus and tissue bit samples were processed as per standard microbiological procedures. Antimicrobial susceptibility test was performed as per Clinical and Laboratory Standards Institute (CLSI) guidelines. Biofilm formation was detected by the tissue culture plate method. Molecular characterisation of resistant pathogens was done by PCR. Variables were expressed as proportions or percentages. Results: Out of 150 diabetic patients, 17.3% of patients underwent amputation. A 90% of patients were associated with anaemia. Most ulcers were polymicrobial in nature. Predominantly isolated pathogens were Pseudomonas aeruginosa 37 (17.1%) and Staphylococcus aureus 33 (15.2%) among aerobic bacteria, Peptostreptococcus 10 (4.6%) among the anaerobes and Candida albicans 20 (9.2%) in fungus. Gram negative bacteria showed high sensitivity to piperacillintazobactam, meropenem, and gram positive cocci to vancomycin and linezolid. A 82% of bacterial isolates and 50% of fungal isolates were biofilm producers. Staphylococcus aureus was a strong biofilm producer. On molecular characterisation, blaCTX-M, blaTEM, blaNDM-1, blaOXA-23, mecA genes were present in resistant biofilm-forming isolates. Conclusion(s): Polymicrobial wound infection and biofilm formation in DFU confers antibiotic resistance and contributes to Multidrug Resistant Organisms (MDRO's). However, proper antibiotic surveillance and antibiotic policy, and preventive strategies can curtail the spread of resistant strains. [ABSTRACT FROM AUTHOR]

AIMS: Diabetic foot ulcer is a dreaded complication of diabetes. Diabetic foot ulcer patients are often infected with multidrug resistant organism (MDRO) due to chronic course of the wound, inappropriate antibiotics treatment, frequent hospital admission, neuropathy, nephropathy, and peripheral vascular disease. MATERIALS AND METHODS: This prospective study was conducted in our 750 bedded hospital for a period of 6 months. The present study was undertaken to isolate various MDRO methicillin resistant Staphylococcus aureus; Gram-negative bacteria producing enzymes such as extended spectrum beta-lactamases (ESBL), Amp C, Carbapenamases; Pseudomonas and Acinetobacter species producing metallo-beta-lactamases (MBL). In addition we attempted to identify risk factors for association of diabetic foot ulcer and MDRO. RESULTS: A total of 149 bacterial isolates were identified. Of the total isolates 73.2% were Gram-negative and remaining 26.8% were Gram-positive bacteria. Among Enterobacteriaceae 59% were ESBL producers and 48% were Amp C producers. In addition, 41.5% of the isolates produced both ESBL and Amp C and 13.4% were carbapenem resistant Enterobacteriaceae. Among 20 Pseudomonas and Acinetobacter isolates, 5 were MBL producers (25%). Furthermore, in the study, 56% of patients with diabetic foot ulcer harbored MDRO. The risk of multidrug-resistant infection is significantly more in patients having diabetes duration >20 years and size of ulcer more than 4 cm2. CONCLUSION: The detection of MDRO in patients of diabetic foot ulcer changes the treatment strategies limits the antimicrobial options and causes higher complications among them.

Abstract Background Several studies have shown a high prevalence of multi-drug resistant organisms (MDRO) amongst asylum seekers when compared to the general population. The aim of this study is to assess the duration of MDRO carriage in this population. Methods Data were retrospectively collected between January 1st 2014 through December 31st 2016. Study material included screening samples for MDRO carriage and clinical samples from asylum seekers in need of medical care. The study focused on methicillin-resistant Staphylococcus aureus (MRSA) and multi-drug resistant Enterobacteriaceae (MDRE). The rates of MRSA and MDRE detected were calculated every four weeks after arrival in the Netherlands. Results Samples from 2091 asylum seekers were included. 1270 (60.7%) were female, median age was 26 years (IQR 20–34) and median number of days in the Netherlands until first sample was 67 (IQR 4–235). In the patients’ first obtained samples, the rate of MRSA varied between 4.5 and 13.0% per time interval after arrival. The rate of MDRE fluctuated between 7.4% and 25.0%. No particular decline in positivity rates in first obtained samples was observed after arrival in the Netherlands. In the group of asylum seekers who arrived more than one year ago, MRSA was isolated in a percentage of 5.1% (n = 273, median months after arrival 34.1 (IQR 16.5–63.1)) and MDRE in 9.4% (n = 276, median months after arrival 35.4 (IQR 17–65)). Conclusion To our knowledge, this is the first study demonstrating that carriage rate of MDRO in asylum seekers remains high even after prolonged stay in the Netherlands. Longitudinal data on MDRO carriage after arrival in countries with a low MDRO prevalence are needed to determine optimal screening strategies, infection control measures and empirical antibiotic therapy.

The emergence of carbapenem-resistant Enterobacteriaceae (CRE) is an important public health issue worldwide, not only due to the potential of these pathogens for widespread dissemination, but also due to the limited antimicrobial therapy options, and the elevated mortality rates associated with these infections. As with other multidrug-resistant organisms (MDROs), active surveillance via timely testing, early diagnosis, and contact isolation is an important strategy to control the occurrence and spread of CRE bacteria. Here we summarize the epidemiology of CRE infections in Japan from 2015 to 2019. Data were extracted from a public dataset collected by the nationwide surveillance system via the National Institute of Infectious Diseases (NIID) of Japan. The annual number of reported CRE infections has remained relatively stable, with a tendency to increase in the last two years (1671 cases reported in 2015 and 2333 cases reported in 2019). The majority of patients who presented CRE infections over this five year period were older than 65 years (~80%, mean age 75), 60% of them were men, and mortality rates were around 3.5%. Importantly, about 60% of infections are caused by both Enterobacter cloacae and Klebsiella aerogenes (previously known as Enterobacter aerogenes), the former being the most common pathogen in 2015 and 2016 (~30%), and the latter the leading pathogen since 2017 (~40%). The most common carbapenemase isolated was the IMP carbapenemase type. Further studies are needed to determine the prevalence of CRE colonization, especially in the healthcare setting, and to elucidate the mechanisms behind the local predominance of Klebsiella aerogenes and Enterobacter cloacae.

Sepsis, a life-threatening organ dysfunction caused by a dysregulated response to infection is a major public health concern, as it is a leading cause of mortality and critical illness worldwide. Antibiotics are one of the cornerstones of the treatment of sepsis; administering appropriate antibiotics in a rapid fashion to obtain adequate drug concentrations at the site of the infection can improve survival of patients. Nevertheless, it is a challenge for clinicians to do so. Indeed, clinicians today are regularly confronted with infections due to very resistant pathogens, and standard dosage regimens of antibiotics often do not provide adequate antibiotic concentrations at the site of the infection. We provide a narrative minireview of different anti-infectious treatments currently available and suggestions on how to deliver optimized dosage regimens to septic patients. Particular emphasis will be made on newly available anti-infectious therapies.

(1) Background: Multidrug-resistant organisms (MDRO) are a growing problem in liver transplant recipients (LTR), associated with high morbidity and mortality. We reviewed the impact of antimicrobial stewardship (AMS) and active screening of MDRO on the epidemiology and outcomes in paediatric LTR. (2) Methods: Single-centre retrospective review of paediatric LTR from January 2017 to December 2018. (3) Results: Ninety-six children were included; 32 (33%) patients were colonised with ≥1 MDRO and 22 (23%) patients had MDRO infections. Median (IQR) duration for start of infection was 9.5 (1.8–16.0) days. Colonisation rate with Gram-positive MDRO was 15.6%, with infection rate of 6.2%; majority due to Vancomycin-Resistant Enterococcus faecium (VRE). Colonisation with Gram-negative MDRO was 27.0%, with infection rate of 16.6%; majority due to extended-spectrum β-lactamase producing Enterobacteriaceae. Colonisation and infection rate due to Carbapenem-resistant Enterobacteriaceae was 6% and 3%, respectively, during screening and AMS, compared to historical control of 25% and 30%, respectively, without screening and AMS. There was significant reduction in VRE and CRE infection during AMS period in comparison to historical control. Pre-transplant risk factors including bacterial infections pre-transplant (p < 0.01), diagnosis of biliary atresia (p = 0.03), exposure to antibiotics (p < 0.01), EBV viraemia (p = 0.01), and auxiliary transplantation (p < 0.01) were associated with post-transplant MDRO infections. Patients with MDRO infections had longer length of hospital and paediatric intensive care unit stay days (p < 0.01) but associated with no mortality. (4) Conclusions: Our results demonstrate low incidence of colonisation and infections with MDRO, which were associated with high morbidity but no mortality in paediatric LTR. There was significant reduction in MRSA, VRE, and CRE during AMS period compared to pre-AMS era. Some risk factors are unavoidable but antibiotic overuse, early initiation of appropriate antibiotic therapy and effective infection prevention strategies can be monitored with multifaceted approach of AMS and screening of MDRO. With limited therapeutic options for MDRO and efficacy data of newer antibiotics in paediatric LTR, robust infection control practices are of paramount importance.

Introduction: Postoperative infections in orthopaedic implants is a major concerning factor. It can lead to the failure of implants and in severe cases can even lead to amputation and mortality. Total joint replacements and fracture fixations do help by reducing the agony of many patients but postoperative infections are a detrimental complication. It is an economic disaster for hospitals that treat large number of these patients therefore identification of risk factors, common pathogens involved, early initiation and prompt use of empirical therapy is necessary to prevent implant failures and also collection of deep tissue samples improves the diagnostic reliability and microbiological yield of implant related infections. Hence, appropriate collection of specimens is a key factor for early diagnosis and differentiating colonisers from true pathogens. Aim: To evaluate the rate of implant related infections, sensitivity of Gram’s stain and its accuracy in tissue samples over wound swabs and also to determine the trends in the antibiogram. Materials and Methods: A retrospective analysis was performed from the samples (tissues and wound swabs) received to the Department of Microbiology from October 1st 2017-October 30th 2018 (a period of one year) in patients with orthopaedic implants. Identification and susceptibility patterns of the bacterial pathogens were identified by the automated Vitek 2 compact system (biomeriux). The data was analysed in terms of frequency and percentage. Results: A total of 141 cases were analysed out of which 45.3% (64/141) were tissue samples and 54.6% (77/141) were wound swabs. Culture positivity observed in tissues was 43.7% (28/64), in wound swabs 50.6% (39/77) and mixed infections were observed in 7.14% (2/28) of tissues and 5.12% (2/39) of wound swabs. Colonisers were observed in 14.2% (11/77) of wound swabs. Specificity of Gram’s stain in comparison with tissue cultures was found to be 83.3% and sensitivity was 50%. Methicillin Sensitive Staphylococcus aureus (MSSA) 17.8% (05/28) and Escherichia coli 21.4% (6/28) were the major pathogens isolated from tissue cultures. Methicillin Resistant Staphylococcus aureus (MRSA) was isolated from 33.3% (13/39) of wound swabs followed by Escherichia coli (28.2%) (11/39). In the present study 25% (7/28) of tissue isolates showed Multidrug Resistance (MDR) and 3.5% (1/28) were Extended Spectrum Beta Lactamase (ESBL) producers. Among wound swabs 23% (9/39) isolates were MDR and 10.2% (4/39) were ESBL producers. Conclusion: In the present study it was observed that tissue samples were found to be better specimens in comparison with wound swabs for the diagnosis of implant infections. Hence, appropriate collection of sample helps in accurate isolation of pathogens in implant infections.

Purpose: The burden of urinary tract infections (UTIs) and risk factors for developing infections with multidrug resistant organisms (MDROs) post‐kidney transplantation (KT) are poorly understood. Methods: Single‐center retrospective cohort study (January 2015‐December 2017) evaluating first and recurrent episodes of bacteriuria and subsequent analysis of episodes caused by MDROs up to 6 months post‐KT. Donor and recipient variables were reviewed. Results: A total of 743 adults underwent single KT during the study period, and 106 patients were hospitalized with bacteriuria. 45% were asymptomatic in their first episode. 73.6% had a single episode, and 26.4% had 2 or more episodes. A total of 28 patients had recurrent episodes; 64.3% had an MDRO on the first episode and 78.6% on the second episode. Escherichia coli was the most common organism isolated, 88.5% were resistant to trimethoprim‐sulfamethoxazole (TMP‐SMX), 9.3% were extended‐spectrum beta‐lactamase (ESBL) producers, and 38.1% were MDROs. Body mass index ≥30 was significantly associated with the presence of MDROs in both univariate and multivariate analyses (RR 1.37, 95% CI 1.01‐1.88; OR 3.26, CI 1.29‐8.25). A total of 12 donors had bacteremia or bacteriuria and 6 (50%) with E coli. A total of 10 KT recipients received antibiotic prophylaxis to prevent donor‐derived infections. Conclusions: Our results suggest that a significant proportion of patients develop recurrent bacteriuria post‐transplantation; of those, more than half caused by MDROs. There is a possible association between obesity and MDROs in KT recipients that merits further investigation. With the global crisis in antimicrobial resistance, innovative strategies are needed to prevent and treat UTIs in KT patients. [ABSTRACT FROM AUTHOR]

• Colistin is used as a last resort for treatment of multidrug-resistant infections. • Colistin was frequently used in combination with a carbapenem. • Nephrotoxicity was a common adverse effect. • Clinical success was modest and overall mortality was high. Colistimethate sodium (colistin) is used to treat multidrug-resistant gram negative infections. We describe the profile and outcomes of patients given colistin in a tertiary level government hospital in Manila, Philippines. We performed a retrospective study of adult patients given intravenous colistin between January 2015 to June 2018 in the Philippine General Hospital. We defined clinical success as a composite of hemodynamic stability, quick Sequential Organ Failure Assessment (qSOFA) score, and microbiological cure. 250 patients were included, half (49.2%) were admitted in the ICU. Median age was 55 years. There was an increase in qSOFA, APACHE II score, and septic shock from baseline to 24 h prior to colistin use. Most patients had pneumonia (90.8%) with extensively drug-resistant Acinetobacter baumannii as the most common isolate (78.8%). Colistin was given in combination with meropenem (96.4%) for a median of 12 days. Nephrotoxicity was seen in 30.8%, with renal replacement therapy needed in 6%. Clinical success was seen in 61.2% of patients and overall mortality was 41.6%. Colistin was frequently used in combination with a carbapenem for treatment of XDR-related respiratory infections. Nephrotoxicity was a common adverse effect. Clinical success was modest and overall mortality was high. [ABSTRACT FROM AUTHOR]

Introduction: Postoperative infections in orthopaedic implants is a major concerning factor. It can lead to the failure of implants and in severe cases can even lead to amputation and mortality. Total joint replacements and fracture fixations do help by reducing the agony of many patients but postoperative infections are a detrimental complication. It is an economic disaster for hospitals that treat large number of these patients therefore identification of risk factors, common pathogens involved, early initiation and prompt use of empirical therapy is necessary to prevent implant failures and also collection of deep tissue samples improves the diagnostic reliability and microbiological yield of implant related infections. Hence, appropriate collection of specimens is a key factor for early diagnosis and differentiating colonisers from true pathogens. Aim: To evaluate the rate of implant related infections, sensitivity of Gram's stain and its accuracy in tissue samples over wound swabs and also to determine the trends in the antibiogram. Materials and Methods: A retrospective analysis was performed from the samples (tissues and wound swabs) received to the Department of Microbiology from October 1st 2017-October 30th 2018 (a period of one year) in patients with orthopaedic implants. Identification and susceptibility patterns of the bacterial pathogens were identified by the automated Vitek 2 compact system (biomeriux). The data was analysed in terms of frequency and percentage. Results: A total of 141 cases were analysed out of which 45.3% (64/141) were tissue samples and 54.6% (77/141) were wound swabs. Culture positivity observed in tissues was 43.7% (28/64), in wound swabs 50.6% (39/77) and mixed infections were observed in 7.14% (2/28) of tissues and 5.12% (2/39) of wound swabs. Colonisers were observed in 14.2% (11/77) of wound swabs. Specificity of Gram's stain in comparison with tissue cultures was found to be 83.3% and sensitivity was 50%. Methicillin Sensitive Staphylococcus aureus (MSSA) 17.8% (05/28) and Escherichia coli 21.4% (6/28) were the major pathogens isolated from tissue cultures. Methicillin Resistant Staphylococcus aureus (MRSA) was isolated from 33.3% (13/39) of wound swabs followed by Escherichia coli (28.2%) (11/39). In the present study 25% (7/28) of tissue isolates showed Multidrug Resistance (MDR) and 3.5% (1/28) were Extended Spectrum Beta Lactamase (ESBL) producers. Among wound swabs 23% (9/39) isolates were MDR and 10.2% (4/39) were ESBL producers. Conclusion: In the present study it was observed that tissue samples were found to be better specimens in comparison with wound swabs for the diagnosis of implant infections. Hence, appropriate collection of sample helps in accurate isolation of pathogens in implant infections. [ABSTRACT FROM AUTHOR]

The worldwide propagation of antimicrobial resistance represents one of the biggest threats to global health and development. Multi-drug-resistant organisms (MDROs), including carbapenem-resistant non-fermenting Gram-negatives and Enterobacterales, present a heterogeneous and mutating spread. Infections by MDRO are often associated with an unfavorable outcome, especially among critically ill populations. The polymyxins represented the backbone of antibiotic regimens for Gram-negative MDROs in recent decades, but their use presents multiple pitfalls. Luckily, new agents with potent activity against MDROs have become available in recent times and more are yet to come. Now, we have the duty to make the best use of these new therapeutic tools in order not to prematurely compromise their effectiveness and at the same time improve patients’ outcomes. We reviewed the current literature on ceftazidime/avibactam, meropenem/vaborbactam and cefiderocol, focusing on antimicrobial spectrum, on the prevalence and mechanisms of resistance development and on the main in vitro and clinical experiences available so far. Subsequently, we performed a step-by-step construction of a speculative algorithm for a reasoned prescription of these new antibiotics, contemplating both empirical and targeted use. Attention was specifically posed on patients with life-risk conditions and in settings with elevated prevalence of MDRO.

INTRODUCTION: Multidrug-resistant organisms (MDROs) have been a major concern in King Saud Medical City (KSMC) recently. The number of cases with colistin resistance was growing rapidly in the first half of 2016, challenging the infection control practices and mandating a thorough outbreak investigation. Objective: determining the extent of the outbreak, identifying risk factors and preventing further increase in the rates of MDROs. METHODS: reviewing the medical records of the 22 admitted cases with colistin resistance using an abstraction form composed of demographical data, comorbidities, details of current admissions, and procedures. Also, tracking patients' movements in the hospital, reviewing all cultures isolates, and reviewing the surveillance and infection control strategies. RESULTS: mean age was 49.71,17.824 (20-79 years), 90.9% were males, 63.6% cases admitted under medical unit. The average duration of stay in the ED was 1.23 day. Over 2/3 had hypertension and diabetes mellitus. Majority of patients staying between 20-40 days in the hospital and the average number of days until developing colistin resistance was 44.18. Resistance was solely related to two organisms that were Acinetobacter baumanni (59.1%) and Klebsiella pneumoniae (40. 9%). Ventilators and folly's catheters were equally (95.5%) used by 21 patients. The most common site of infection was respiratory (41.3%), of which most were sputum samples. Resistance of over 75% is recorded by Antibiotics like Tazocin, Ciprofloxacin, Imepenen and oxacillin. CONCLUSION: the uncontrolled use of antibiotics, prolonged stay in the Intensive Care Unit (ICU), frequent uses of different devices, are the potential risk factors of developing colistin resistance.

Introduction: multidrug-resistant organisms (MDROs) have been a major concern in King Saud Medical City (KSMC) recently. The number of cases with colistin resistance was growing rapidly in the first half of 2016, challenging the infection control practices and mandating a thorough outbreak investigation. The objective of this study was to determine the extent of the outbreak, identify potential risk factors and prevent further increase in the rates of MDROs. Methods: reviewing the medical records of the 22 admitted cases with colistin resistance using an abstraction form composed of demographical data, comorbidities, details of current admissions, and procedures. Also, tracking patients' movements in the hospital, reviewing all cultures isolates, and reviewing the surveillance and infection control strategies. Results: mean age was 49.71±17.824 (20-79 years), 90.9% were males, 63.6% cases admitted under medical unit. The average duration of stay in the ED was 1.23 day. Over 2/3 had hypertension and diabetes mellitus. Majority of patients staying between 20-40 days in the hospital & the average number of days until developing colistin resistance was 44.18. Resistance was solely related to two organisms that were Acinetobacter baumanni (59.1%) and Klebsiella pneumoniae (40. 9%). Ventilators and folly's catheters were equally (95.5%) used by 21 patients. The most common site of infection was respiratory (41.3%), of which most were sputum samples. Resistance of over 75% is recorded by antibiotics like tazocin, ciprofloxacin, imepenen and oxacillin. Conclusion: the uncontrolled use of antibiotics, prolonged stay in the Intensive Care Unit (ICU), frequent uses of different devices, are the potential risk factors of developing colistin resistance. [ABSTRACT FROM AUTHOR]

The article presents a study which evaluated data on phages that may prevent and eradicate the Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE) pathogens in humans. Topics discussed include page efficacy and safety, numbers of available studies of phage therapy against ESKAPE pathogens in human, and recommendations for successful phage therapy in clinical settings.

• Necrotizing fasciitis of the head and neck in children is very rare. • Proper early diagnosis and adequate antibiotic therapy played an important role. • Early aggressive surgical treatment is crucial for an adequate outcome. • The vacuum-assisted closure and hyperbaric oxygen therapy are very useful to accelerate wound healing. • A multidisciplinary management is fundamental to increase treatment success. Necrotizing fasciitis (NF) is a severe infectious condition associated with significant morbidity and mortality and characteristically has a higher incidence in adults; pediatric cases are very rare. In this case report we describe, the clinical presentation, management and outcome of a patient with necrotizing fasciitis of the neck and head complicated with chronic osteomyelitis. An 18 month-old, latin, male, diagnosed with rickets and Crouzon syndrome, twenty-four hours post- craniofacial remodeling surgery presented tissue edema, indurated skin and violaceous and well delimited lesions in the neck and head. The patient developed septic shock, acute osteomyelitis and infection of the cranial grafts. Multiple surgical lavages, debridation of the necrotic tissue and resection of the affected bone, in combination with multiple antibiotics, laboratory test methods, VAC therapy and hyperbaric oxygen were required for successful treatment and full recovery of the patient. Although early antibiotic therapy and critical care are basic for the treatment of patients with NF, early aggressive surgical treatment is crucial for an adequate outcome. Adjuvant treatment for NF such as the Vacuum-assisted closure and the hyperbaric oxygen therapy are very useful to accelerate wound healing. Moreover, special laboratory test methods such as the checkerboard can be used to determine the adequate antimicrobial combination of drugs in the case of multi resistant organisms. Early diagnosis, adequate antibiotic therapy and aggressive surgical debridement of the necrotic tissue combined with VAC and hyperbaric oxygen therapy played an important role in the successful treatment of NF. [ABSTRACT FROM AUTHOR]

AIMS: Diabetic foot ulcer is a dreaded complication of diabetes. Diabetic foot ulcer patients are often infected with multidrug resistant organism (MDRO) due to chronic course of the wound, inappropriate antibiotics treatment, frequent hospital admission, neuropathy, nephropathy, and peripheral vascular disease. MATERIALS AND METHODS: This prospective study was conducted in our 750 bedded hospital for a period of 6 months. The present study was undertaken to isolate various MDRO methicillin resistant Staphylococcus aureus; Gram-negative bacteria producing enzymes such as extended spectrum beta-lactamases (ESBL), Amp C, Carbapenamases; Pseudomonas and Acinetobacter species producing metallo-beta-lactamases (MBL). In addition we attempted to identify risk factors for association of diabetic foot ulcer and MDRO. RESULTS: A total of 149 bacterial isolates were identified. Of the total isolates 73.2% were Gram-negative and remaining 26.8% were Gram-positive bacteria. Among Enterobacteriaceae 59% were ESBL producers and 48% were Amp C producers. In addition, 41.5% of the isolates produced both ESBL and Amp C and 13.4% were carbapenem resistant Enterobacteriaceae. Among 20 Pseudomonas and Acinetobacter isolates, 5 were MBL producers (25%). Furthermore, in the study, 56% of patients with diabetic foot ulcer harbored MDRO. The risk of multidrug-resistant infection is significantly more in patients having diabetes duration >20 years and size of ulcer more than 4 cm2. CONCLUSION: The detection of MDRO in patients of diabetic foot ulcer changes the treatment strategies limits the antimicrobial options and causes higher complications among them. [ABSTRACT FROM AUTHOR]

Antibiotics have revolutionized human and animal healthcare, but their utility is reduced as bacteria evolve resistance mechanisms over time. Thankfully, there are novel antibiotics in the pipeline to overcome resistance, which are mentioned elsewhere in this special issue, but eventually bacteria are expected to evolve resistance to most new compounds as well. Multidrug resistant organisms (MDROs) that cause infections increase morbidity, mortality, and readmissions as compared with susceptible organisms. Consequently, many research and development pipelines are focused on non-antibiotic strategies, including fecal microbiota transplantation (FMT), probiotics and prebiotics, and a range of therapies in between. Studies reviewed here focus on efforts to directly treat or prevent MDRO infections or colonization. The studies were collected through clinicaltrials.gov, PubMed, and the International Conference on the Harmonisation Good Clinical Practice website (ichgcp.net). While the gold standard of clinical research is randomized controlled trials (RCTs), several pilot studies are included because the field is so young. Although a vast preclinical body of research has led to studies in humans, animal and in vitro studies are not within the scope of this review. This narrative review discusses microbiome-modifying therapies targeting MDROs in the gut and includes current results, ongoing clinical trials, companies with therapies in the pipeline specifically for MDROs, and commentary on clinical implementation and challenges.

Background Data from northeast India regarding health care associated infections (HAI) is limited. Objective To determine the incidence, determinants, clinical and microbiological profile of healthcare associated pneumonia and urinary tract infection (UTI). Methods and material Prospective, observational study was conducted in 150 patients with HAI, aged ≥18 years, selected randomly. HAI was defined by CDC criteria. Controls comprised of 150 age and sex matched patients without HAI. Data was analysed using SPSS-17.0 and p value <0.05 was considered significant. Results Mean age was 54.3 ± 17.2 years with male:female ratio of 3:2. Most patients (66%) were aged ≥50 years. Overall incidence of HAI was 11.06%. Most common causative organisms for healthcare associated UTI and pneumonia were E. coli (34.8%) and Klebsiella (37.7%) respectively. Compared to controls, patients with HAI had significantly higher co-morbidities (57.3% vs. 18.7%, p < 0.001); increased use of invasive devices (p < 0.05); increased use of quinolones, piperacillin-tazobactam, carbapenem; longer stay in the ICU (12.04 vs. 6.02 days, p < 0.01) and increased in-hospital mortality (27.3% vs. 5%, p < 0.01). Conclusion HAI are more common in patients aged ≥50 years, having co-morbidities, resulting in increased hospital stay and poorer outcomes. The incidence of HAI and isolation of multidrug resistant organisms are lower than other studies. [ABSTRACT FROM AUTHOR]

Background Although not all health care-associated infections (HAIs) are preventable, reducing HAIs through targeted intervention is key to a successful infection prevention program. To identify areas in need of targeted intervention, robust statistical methods must be used when analyzing surveillance data. The objective of this study was to compare and contrast statistical process control (SPC) charts with Twitter's anomaly and breakout detection algorithms. Methods SPC and anomaly/breakout detection (ABD) charts were created for vancomycin-resistant Enterococcus , Acinetobacter baumannii, catheter-associated urinary tract infection, and central line-associated bloodstream infection data. Results Both SPC and ABD charts detected similar data points as anomalous/out of control on most charts. The vancomycin-resistant Enterococcus ABD chart detected an extra anomalous point that appeared to be higher than the same time period in prior years. Using a small subset of the central line-associated bloodstream infection data, the ABD chart was able to detect anomalies where the SPC chart was not. Discussion SPC charts and ABD charts both performed well, although ABD charts appeared to work better in the context of seasonal variation and autocorrelation. Conclusions Because they account for common statistical issues in HAI data, ABD charts may be useful for practitioners for analysis of HAI surveillance data. [ABSTRACT FROM AUTHOR]