Microbiological Susceptibility Research Articles

Clinical spectrum, phenotypic and molecular characterization, and antifungal susceptibility of an emerging human pathogen, Acrophialophora, from India.

Acrophialophora is implicated in superficial and invasive infections, especially in immunosuppressed individuals. The present study was undertaken to provide clinical, microbiological, phylogenetic, and antifungal susceptibility testing (AFST) profile of Acrophialophora isolated from India. All the isolates identified as Acrophialophora species at the National Culture Collection for Pathogenic Fungi, Chandigarh, India were revived. Phenotypic and molecular characterization was performed, followed by temperature studies, scanning electron microscopy (SEM), and AFST. We also performed systematic review of all the cases of Acrophialophora species reported till date. A total of nine isolates identified as Acrophialophora species were identified by molecular method as A. fusispora (n=8) and A. levis (n=1), from brain abscess (n=4), respiratory tract (n=3), and corneal scraping (n=2). All patients but two had predisposing factors/co-morbidities. Acrophialophora was identified as mere colonizer in one. Temperature studies and SEM divulged variation between both species. Sequencing of the internal transcribed spacer ribosomal DNA and beta-tubulin loci could distinguish species, while the LSU ribosomal DNA locus could not. AFST showed the lowest minimum inhibitory concentrations (MICs) for triazoles and the highest for echinocandins. Systematic literature review revealed 16 cases (11 studies), with ocular infections, pulmonary and central nervous system infections, and A. fusispora was common species. All the patients except three responded well. High MICs were noted for fluconazole, micafungin, and caspofungin. This is the first study delineating clinical, phenotypic, and genotypic characteristics of Acrophialophora species from India. The study highlights microscopic differences between both species and emphasizes the role of molecular methods in precise identification. Triazoles appear to be the most effective antifungals for managing patients.

Microbiological Profile and Susceptibility Pattern of Bacterial Blood Culture Isolates in COVID-19 Patients with Septicemia from a Designated COVID Hospital in Pune

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.

505 Fusarium Isolates in Burn-injured Patients: Clinical Characteristics and Susceptibility Patterns

Abstract Introduction Fusarium species are ubiquitous in the environment and can cause opportunistic infections in burn-injured patients. Patients with larger burns, prolonged lengths of stay, concomitant antimicrobial use and invasive lines are at higher risk for Fusarium infections. Little data exists on clinical characteristics and in vivo antifungal susceptibilities in burn-injured patients. Methods All positive Fusarium species cultures were retrospectively identified between November 2017 to June 2023 at a regional burn center. Demographic, clinical and microbiologic susceptibility data was collected from the electronic medication record. Descriptive statistics were used to describe the cohort. Results A total of 18 patients had positive Fusarium wound cultures during the study period. The average age was 38.4 ± 11.9 years. The average %TBSA was 54.5 ± 23.4 % and R-Baux score of 92.9 ± 29.3. The most common mechanism of injury was thermal burn (17 patients, 94%). This cohort experienced prolonged ICU (68.9 ± 31.9 days) and hospital (73.6 ± 38.2 days) lengths of stay. The average time from burn injury to positive Fusarium cultures was 19.6 ± 9.0 days. Mechanical ventilation was prolonged (46.1 ± 23.3 days). The average central line duration prior to Fusarium infection was 9.8 ± 10.2 days. Susceptibility data was obtained for voriconazole in 15 patients and for amphotericin in 14 patients. For voriconazole, 5/15 tested isolates had an MIC of 4, 1/15 had an MIC of 8, and 9/15 (60%) isolates returned with MIC ≥ 16. A majority (13/14, 93%) of the MICs tested for amphotericin were ≤ 1. Patients were taken to the OR for source control in all cases. Ten of 18 patients with Fusarium positive infections survived to hospital discharge (55%). The most common cause of death was multi-system organ failure and sepsis (88%). Recorded adverse drug events possibly due to voriconazole and posaconazole included transaminitis (4 cases), QTc prolongation (1 case), and hallucinations (1 case). Amphotericin was suspected of contributing to an acute kidney injury in 1 case. Conclusions This case series reports the clinical characteristics and susceptibility data on Fusarium isolates in a burn-injured population. This cohort was critically ill based on the %TBSA, R-Baux score, and high rate of mechanical ventilation. The MIC results obtained for voriconazole demonstrated a majority of isolates with relatively high MIC values ≥ 16. A majority of the MICs for amphotericin were < 1. It is important to note that no established breakpoints exist for Fusarium species and clinical outcomes are dependent on a variety of factors beyond the susceptibility data. Applicability of Research to Practice Empiric double coverage with voriconazole and amphotericin or amphotericin monotherapy should be considered when Fusarium is a suspected primary pathogen.

Microbiological and Antimicrobial Susceptibility Pattern of Asymptomatic Bacteriuria in Pregnant Women Attending SQUH.

Our research aimed to study the microbiology and antimicrobial resistance in asymptomatic bacteriuria (ASB) among Omani pregnant women. We conducted a retrospective study that included data from 196 Omani pregnant women with ASB who received care at Sultan Qaboos University Hospital from 2010-2019. Data were obtained from the patients' electronic medical records including demographics, clinical details, isolated organisms, antimicrobial susceptibility results, and prescribed antibiotics. ASB was detected in 56.1% of cases during the third trimester. Klebsiella pneumoniae(32.1%) was the most frequently isolated organism, followed by Escherichia coli (29.6%). Twenty-one (10.7%) isolates were extended-spectrum beta-lactamase (ESBL)-producing organisms. The overall microbiological susceptibility pattern showed that organisms have a high susceptibility rate to nitrofurantoin reaching 82.8%, followed to a lesser extent by cefuroxime and augmentin. The susceptibility of E. coli and K. pneumoniae to cefuroxime was 74.1% and 71.4%, respectively. Only 52.4% of all isolated ESBL-producing organisms were susceptible to nitrofurantoin. K. pneumoniae and E. coli were the most frequently isolated bacteria in ASB, representing 60.7% of total isolates. A high prevalence of ESBL-producing organisms, 10.7% of the total isolates, was observed. Cefuroxime is an appropriate empirical antibacterial therapy for ASB and urinary tract infection in pregnant women. Nitrofurantoin should be considered for empirical antibiotic therapy in settings of high prevalence of ESBL-producing organisms.

Comparison of Cefazolin and Ceftriaxone Enterobacterales Susceptibilities for Inpatient Treatment of Urinary Tract Infections and Risk of Hospital-onset Clostridioides difficile Infection

Purpose: Urinary tract infection (UTI) is the second most common indication for antibiotic therapy among inpatients in the United States. Ceftriaxone, a third-generation cephalosporin, is habitually chosen to treat inpatient UTIs due to familiarity, cost and perceived safety. However, third-generation cephalosporins increase the risk of healthcare facility-onset Clostridioides difficile infection (HOCDI) more than any other antibiotic group, while no statistical risk exists for first-generation cephalosporins. Recent evidence comparing Enterobacterales susceptibility for first- and third-generation cephalosporins in urinary specimens in the United States does not exist. This analysis assesses comparative activity of cefazolin and ceftriaxone for Enterobacterales urinary isolates and incidence of HOCDI to determine the usefulness of cefazolin as an empiric agent to manage inpatient UTI and limit ceftriaxone collateral damage.Methods: This is a retrospective single center observational study. Microbiologic susceptibility data was analyzed for E. coli, K. pneumoniae, and P. mirabilis urinary specimens taken from adult inpatients admitted January 1, 2022 to December 31, 2022. Primary outcome is incidence of E. coli, K. pneumoniae, and P. mirabilis susceptibility to cefazolin in uncomplicated UTI (MIC < 16 mcg/mL). Secondary outcomes include susceptibility for complicated UTI and HOCDI risk associated with cefazolin and ceftriaxone. A larger time frame, January 1, 2016 to December 31, 2022, was used to assess HOCDI risk associated with cefazolin and ceftriaxone. HOCDI risk assessment included adults administered at least one dose of either cefazolin or ceftriaxone during a minimum of four-day hospitalization.Findings: A total of 1150 urine samples were identified as E. coli, K. pneumoniae, and P. mirabilis in 2022. Susceptibility to cefazolin was observed in 1064/1150 (92.5%) isolates using the MIC breakpoint for uncomplicated UTI, and to ceftriaxone in 1115/1150 (97.0%) isolates (p < 0.001). From 2016-2022, either cefazolin or ceftriaxone was administered in 26,462 inpatient admissions with an HOCDI diagnoses occurring in 89 admissions. HOCDI developed in 78 admissions (0.40%) with ceftriaxone exposure and 11 cases (0.15%) developed in cefazolin exposed admissions (p < 0.001, adjusted OR 2.44, 95% CI 1.25 – 4.76).Implications: Cefazolin demonstrates high susceptibility for uropathogens commonly implicated in uncomplicated UTI, the predominant UTI managed inpatient. While ceftriaxone demonstrates a higher susceptibility rate against these common uropathogens, it more than doubles the risk for HOCDI compared to cefazolin. For institutions evaluating opportunities to reduce ceftriaxone use to limit associated collateral damage like HOCDI, use of cefazolin for uncomplicated urinary tract infection may be evaluated using local susceptibility data.

Phenotypic and Genotypic Characterization of Pan-Drug-Resistant Klebsiella pneumoniae Isolated in Qatar.

In secondary healthcare, carbapenem-resistant Enterobacterales (CREs), such as those observed in Klebsiella pneumoniae, are a global public health priority with significant clinical outcomes. In this study, we described the clinical, phenotypic, and genotypic characteristics of three pan-drug-resistant (PDR) isolates that demonstrated extended resistance to conventional and novel antimicrobials. All patients had risk factors for the acquisition of multidrug-resistant organisms, while microbiological susceptibility testing showed resistance to all conventional antimicrobials. Advanced susceptibility testing demonstrated resistance to broad agents, such as ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam. Nevertheless, all isolates were susceptible to cefiderocol, suggested as one of the novel antimicrobials that demonstrated potent in vitro activity against resistant Gram-negative bacteria, including CREs, pointing toward its potential therapeutic role for PDR pathogens. Expanded genomic studies revealed multiple antimicrobial-resistant genes (ARGs), including blaNMD-5 and blaOXA derivative types, as well as a mutated outer membrane porin protein (OmpK37).

Chronic Suppurative Otitis Media: A Prospective Descriptive Study of the Microbiology and Antimicrobial Susceptibility Patterns.

This study aims to identify dominant causative pathogens of chronic suppurative otitis media (CSOM) and their antimicrobial susceptibility patterns. The secondary objective is to assess the cholesteatoma concurrence among this population. A prospective descriptive study. Port Elizabeth Provincial Hospital, Eastern Cape, South Africa. Aural swabs of purulent otorrhoea were collected from patients with CSOM attending the otorhinolaryngology outpatient department between April 2022 and June 2023. Samples were analyzed to determine the microbiological spectrum and evaluate antimicrobial sensitivities. Patient files were reviewed to identify cases with cholesteatoma. The study population size of 169 enabled representative results for a confidence interval of 90%. Patients were divided into 2 age categories: children (0-12 years) and adults (>12 years). Adults represented the majority of cases (76.9%) and females (58.6%) were affected more than males. Fungal isolates, Candida species and Aspergillus species, were the most common (20.8%). This was followed by Pseudomonas aeruginosa (12.4%) and Staphylococcus aureus (11.8%). 3.6% of cases cultured Mycobacterial tuberculosis which was high compared to global estimates. Susceptibility patterns showed 94.3% sensitivity of fungal cultures to fluconazole. Pseudomonas aeruginosa was 100% susceptible to piperacillin-tazobactam and cefepime, but only 76.2% sensitive to ciprofloxacin. Cholesteatoma concurrence was identified in 17.8%. CSOM remains a public health challenge. This study highlights the need to consider fungal etiology in instances where standard antibiotic treatments prove ineffective. Given the variety of cultured organisms and their susceptibility patterns, incorporating culture-directed therapy should be considered standard practice for chronic otorrhoea patients.

The Microbiological Profile and Antibiotic Susceptibility of Fracture Related Infections in a Low Resource Setting Differ from High Resource Settings: A Cohort Study from Cameroon.

Fracture-related infection (FRI) is a common and devastating complication of orthopedic trauma in all settings. Data on the microbiological profile and susceptibility of FRI to antibiotics in low-income countries are scarce. Therefore, this study aimed to investigate the microbial patterns and antimicrobial susceptibility of FRI in a sub-Saharan African setting in order to provide guidance for the formulation of evidence-based empirical antimicrobial regimens. We conducted a retrospective analysis of patients treated for FRI with deep tissue sampling for microbiological culture from January 2016 to August 2023 in four tertiary-level hospitals in Yaoundé, Cameroon. There were 246 infection episodes in 217 patients. Cultures were positive in 209 (84.9%) cases and polymicrobial in 109 (44.3%) cases. A total of 363 microorganisms from 71 different species were identified, of which 239 (65.8%) were Gram-negative. The most commonly isolated pathogens were Staphylococcus aureus (n = 69; 19%), Enterobacter cloacae (n = 43; 11.8%), Klebsiella pneumoniae (n = 35; 9.6%), Escherichia coli (n = 35; 9.6%), and Pseudomonas aeruginosa (n = 27; 7.4%). Coagulase-negative staphylococci (CoNS) were isolated in only 21 (5.9%) cases. Gram-negative bacteria accounted for the majority of the infections in early (70.9%) and delayed (73.2%) FRI, but Gram-positive bacteria were prevalent in late FRI (51.7%) (p < 0.001). Polymicrobial infections were more frequent in the early (55.9%) and delayed (41.9%) groups than in the late group (27.6%) (p < 0.001). Apart from Staphylococcus aureus, there was no significant difference in the proportions of causative pathogens between early, delayed, and late FRI. This study found striking resistance rates of bacteria to commonly used antibiotics. MRSA accounted for 63% of cases. The most effective antibiotics for all Gram-positive bacteria were linezolid (96.4%), vancomycin (92.5%), clindamycin (85.3%), and fucidic acid (89.4%). For Gram-negative bacteria, only three antibiotics displayed a sensitivity >50%: amikacin (80.4%), imipenem (74.4%), and piperacillin + tazobactam (57%). The most effective empirical antibiotic therapy (with local availability) was the combination of vancomycin and amikacin or vancomycin and imipenem. In contrast to the literature from high-resource settings, this study revealed that in a sub-Saharan African context, Gram-negative bacteria are the most common causative microorganisms of FRI. This study revealed striking resistance rates to commonly used antibiotics, which will require urgent action to prevent antimicrobial resistance in low and middle-income countries.

Risk factors for resistant gram-positive bacteremia in febrile neutropenic patients with cancer

BackgroundGram-positive bacteria are frequently resistant to empirical beta‐lactams in febrile neutropenic patients with cancer. As microbiology and antibiotic susceptibility changes, we reevaluated the risk factors for resistant Gram-positive bacteremia in febrile neutropenic patients with cancer. MethodsEpisodes of bacteremic febrile neutropenia in Seoul National University Hospital from July 2019 to June 2022 were reviewed. Resistant Gram-positive bacteria were defined as a pathogen susceptible only to glycopeptide or linezolid in vitro (e.g., methicillin-resistant staphylococci, penicillin-resistant viridans streptococci, and ampicillin-resistant enterococci). Episodes were compared to identify independent risk factors for resistant Gram-positive bacteremia. ResultsOf 225 episodes, 78 (34.7%) involved resistant Gram-positive bacteremia. Multivariate analysis revealed that breakthrough bacteremia while being administered antibiotics (adjusted odds ratio [aOR], 6.794; 95% confidence interval [95% CI], 3.130–14.749; P < 0.001) and catheter-related infection (aOR 4.039, 95% CI 1.366–11.946; P = 0.012) were associated with resistant Gram-positive bacteremia. Chronic liver disease (aOR 0.231, 95% CI 0.059–0.905; P = 0.035) and hypotension at bacteremia (aOR 0.454, 95% CI 0.218–0.945; P = 0.035) were inversely associated with resistant Gram-positive bacteremia. ConclusionsResistant Gram-positive bacteria should be considered in breakthrough bacteremia and catheter-related infection in febrile neutropenic patients with cancer.

Study of Colistin Resistant Gram Negative Organism in Hospitalized Patients: A Retrospective Study.

Intensive care units have become hotspots for antimicrobial resistance, particularly concerning colistin resistance, posing a threat of untreatable infections. This study aims to analyze the epidemiological and clinical aspects of patients carrying colistin-resistant organisms. It focuses on identifying risk factors, the microbiological profile, susceptibility patterns, and treatment outcomes. Isolates with colistin MIC >2 µg/mL, identified via BD PHOENIX, were subjected to colistin broth disc elution testing (as per CLSI guidelines) in our Microbiology Department between January and December 2022. Among the 30 patients, colistin-resistant gram-negative isolates were found predominantly in blood cultures (50%), followed by ET/TT cultures (23.3%), urine cultures (10%), and other sites (16.7%). Klebsiella pneumoniae was the most common organism (80%), showing the highest sensitivity to Ceftazidime-avibactam + Aztreonam (CAZ-AVI + ATM) (76.7%). Of these patients, 66.7% recovered and were discharged, while 33.3% succumbed during hospitalization despite treatment. The study underscores a notable presence of colistin-resistant gram-negative isolates, predominantly in blood cultures, with K. pneumoniae being predominant. The combination of CAZ-AVI + ATM exhibited the highest sensitivity. However, the mortality rate of 33.3% despite sensitive antibiotic treatment highlights the urgency for ongoing vigilance and research to combat colistin-resistant infections and improve patient outcomes. Diwane D, Rajhans PA, Jog SA, Dalvi M. Study of Colistin Resistant Gram Negative Organism in Hospitalized Patients: A Retrospective Study. Indian J Crit Care Med 2024;28(3):286-289.

Microbiology and Antimicrobial Susceptibility in Adult Dacryocystitis.

To investigate the microbiology and antimicrobial susceptibility of dacryocystitis in adults and identify the changing trends over time in Taiwan. This is a single-centered, retrospective study. We retrospectively reviewed adult patients with dacryocystitis from January 2012 to December 2021 in a tertiary medical center in Taiwan. The pathogens and in vitro antimicrobial susceptibility of the pus cultures from the lacrimal sac were collected. Thirty-five cultures in acute and 211 cultures in chronic dacryocystitis were collected. Of the 220 isolates, a similar proportion of gram-positive (44%) and gram-negative (43%) aerobes were demonstrated in chronic dacryocystitis and more gram-negative aerobes (50%) than gram-positive aereobes (41%) in acute dacryocystitis. The most common pathogens were methicillin-resistant Staphylococcus aureus (MRSA; 28.1%) and Pseudomonas aeruginosa (28.1%) in acute dacryocystitis, while coagulase-negative Staphylococci was the most common micro-organism in chronic dacryocystitis. The effective antibiotics for gram-positive aerobes were vancomycin (100%), moxifloxacin (88%) and trimethoprim/sulfamethoxazole (78%). Meropenem (95%), amikacin (93%), and levofloxacin (91%) were sensitive to more than 90% of gram-negative aerobes in current study. High resistant species were also isolated in our cohort. More gram-negative pathogens and more resistant species are rising in adult dacryocystitis. Understanding the bacteriology and antimicrobial susceptibility of the region is crucial for the empirical antibiotic selection in clinical practice.

Evaluation of Microbiological Susceptibility and Long-term Adhesive Properties to Dentin of Primers with Terminalia catappa Linn.

To investigate the antibacterial effects of Terminalia catappa Linn (TCL) leaf extracts at different concentrations and the effects of these extracts used as primers on the long-term adhesive properties of two universal adhesives. After extract preparation, the antimicrobial and antibacterial activities of TCL against Streptococcus mutans (UA 159) were assessed in microdilution assays to provide the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). Additionally, to provide quantitative data on the ability of TCL extract to reduce cell viability, colony forming units (CFU) were counted. To examine adhesive properties, 288 human molars were randomly assigned to 32 experimental conditions (n = 9) according to the following variables: (1) treatment agent: negative control (untreated surface), and primers at concentrations of 1xMIC, 5xMIC, and 10xMIC; (2) adhesives: Scotchbond Universal (SBU) and Futurabond Universal (FBU); (3) adhesive strategy: etch-and-rinse (ER) or self-etch (SE); and (4) storage time: 24 h or after 2 years. Primers were applied for 60 s, upon which the teeth were incrementally restored and sectioned into adhesive-dentin bonded sticks. These were tested for microtensile bond strength (μTBS) and nanoleakage (NL) after 24-h and 2-year water storage, as well as in-situ degree of conversion (DC) at 24 h. The chemical profile of the hybrid layer was determined via micro-Raman spectroscopy. Biofilm assay data were analyzed using the Kruskal-Wallis test; the pH of culture media and the chemical profile were analyzed by one-way ANOVA. The adhesive properties (µTBS, NL, DC) were evaluated using a four-way ANOVA and Tukey's test. Significance was set at 5%. Similar values of MIC and MBC were observed (2 mg/ml), showing bactericidal potential. CFU analysis demonstrated that concentrations of 5xMIC and 10xMIC significantly inhibited biofilm formation (p < 0.001). The application of the TCL primer at all concentrations significantly increased the immediate μTBS and DC, and decreased the immediate NL values when compared to the control group (p < 0.05), regardless of the adhesive and adhesive strategies. Despite an increase in the NL values for all groups after 2 years (p > 0.05), in groups where the TCL primer was applied, the μTBS remained constant after 2 years for both adhesives, while a decrease in the μTBS was observed in the control groups (p < 0.05). Usually, 10xMIC showed better results than 1xMIC and 5xMIC (p < 0.05). The application of TCL promoted cross-linking; cross-linking rates increased proportionally to the concentration of TCL (p < 0.05). Primers containing TCL promoted bactericidal and bacteriostatic action, as well as cross-linking with dentin, while maintaining the adhesive properties of the adhesive-dentin interface after 2 years of water storage.

P15 UK Antimicrobial Registry Study: progress to date

Abstract Background Effective antimicrobial stewardship is key in the fight against antimicrobial resistance, a key element of which is the surveillance of antimicrobial use and antimicrobial resistance. In addition to quantitative analysis of antibiotic use trends it is also important to understand qualitative aspects of how antimicrobials are used in routine clinical settings. Objectives The UK Antimicrobial Registry (UKAR) Study, a 5 year collaboration between BSAC and the University of Aberdeen, aims to determine how recently licensed antimicrobial agents are being used, their effectiveness and safety. The study is included in the NIHR portfolio in England with similar arrangements in Scotland and Wales. Here, we present brief information on the first few months of participant recruitment. Methods The study commenced recruiting patients prescribed selected antibiotics in May 2023. The intention was to commence with a small number of pilot hospital sites then to expand to a larger number of hospitals. Adult patients are potentially eligible if they have been prescribed any drug on the eligible drug list within their current stay in hospital unless the drug is actively withdrawn after less than 24 h. Data are collected from the medical records of participants who have given informed consent. Clinical data, including infection, microbiology susceptibility testing, eligible drug and dosing regimens are collected as well as prior and concurrent antibiotic therapy. Results As of November 2023, the study is open to recruitment in nine sites across the UK. There are a further 22 sites across the UK in study set-up and a further 15 sites who have submitted an expression of interest to join the registry. Fifty-two patients have been recruited as of November 2023. Five of the 11 study drugs were prescribed; the majority of the participants (N=29) were prescribed dalbavancin, the remainder received various Gram-negative agents (Table 1). Study drugs were used to treat bone and joint infections (33%) and lower respiratory tract infections (33%), with other disease areas including skin and subcutaneous tissue infections and urinary tract infections. Conclusions A key objective for UKAR pilot sites was to verify that the data collection process was feasible and address any issues around clarity of responses. Very few issues were identified, and all were resolved quickly. Early data show that participants are most likely to be female with a median age above 60 years. There is also, currently, a preponderance of patients commencing dalbavancin, although the study is still in its infancy. As more sites recruit participants to the UKAR Study, more detailed analyses can be performed on the clinical usage and outcomes being achieved. Also, follow-up data including clinical outcomes and adverse events will be collected 56 days after commencing therapy, and 28 days after last administration of an eligible study drug. In addition, clinical outcomes and relapse of the initial infection will be recorded at 6 and 12 months.

Analysis of Healthcare-associated Infections before and during the COVID-19 pandemic in a Colombian hospital

Introduction: Healthcare-associated infections pose a significant challenge, contributing to hospital morbidity and mortality. Objective: To describe the behavior of Healthcare Associated Infections before and during the pandemic reported to a high-complexity health institution in Colombia. Material and Methods: In our retrospective observational study on Healthcare-Associated Infections (HAIs), we analyzed data from all in-patients diagnosed with HAIs between 2018 and 2020. This included clinical, demographic, microbiological, and microbial susceptibility information collected from the Committee on Nosocomial Infections' prospective database. Data from 391 isolates were obtained using Whonet software for antimicrobial resistance surveillance. Results: We found 504 cases of HAIs (2018-2020) with an overall in-hospital infection rate of 2.55/1000 patient-days. The median age for pediatric patients was 5 years, and for adults, 56 years, with 57% male. The leading admission diagnoses were oncologic disease complications (31%). Bacteremia had a 30-day mortality rate of 13%, predominantly catheter-associated (37%). Gram-negative bacilli, notably Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa, represented 58% cases of HAI. Discussion: The critical need for specific interventions and antimicrobial management to control HAIs, especially given the challenges posed by the COVID-19 pandemic, is highlighted. Conclusions: This is the first report on HAIs incidence at a tertiary hospital in Bucaramanga, Santander (Colombia). Bacteremia was predominant; 75% of HAIs patients had comorbidities. Gram-negative bacilli prevailed; a notable rise in ICU respiratory infections occurred during the 2020 COVID-19 pandemic. Resistance to cephalosporins and carbapenems was prevalent.

Bacteriological Profile of Bloodstream Infections in Paediatric Oncology Patients with Febrile Neutropenia: A Five-year Ambispective Study at a Tertiary Care Centre in Northern India

Introduction: Bloodstream Infections (BSI) are known to be responsible for significant mortality and morbidity. Cancer patients, being immunosuppressed, are more vulnerable to developing infections and often present with Febrile Neutropenia (FN). Aim: To determine the epidemiology, microbiology, and antibiotic susceptibility pattern among paediatric cancer patients admitted with FN. Materials and Methods: This ambispective study was conducted over a period of 5 years, from April 2018 to April 2023, in the Department of Paediatric Oncology in coordination with the Department of Microbiology at Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India. Isolates collected from April 2018 to April 2022 were retrospectively evaluated with respect to gender, age, and severity of neutropenia, whereas those analysed prospectively were from May 2022 to April 2023. Data from 328 patients presenting with 420 episodes of FN were obtained, including information on age, gender, the organism isolated, and antibiotic susceptibility pattern. Blood samples were collected in blood culture bottles and incubated at 35±2°C in the automated BACT/ALERT blood culture system. Positive bottles were further subjected to manual identification and antibiotic susceptibility testing of the bacterial isolates using the Kirby Bauer disk diffusion method. The results were interpreted according to the Clinical and Laboratory Standards Institute guidelines of 2023. All statistical analyses were performed using Statistical Package for Social Sciences (SPSS) software v.23. Results: A total of 328 patients were admitted over the five- year period, with 420 episodes of FN. The culture positivity rate was 81 out of 420 (19.2%). Among the patients, 50 (61.7%) were males, and 36 (45%) had moderate neutropenia at the time of admission. The most common malignancy was Acute Lymphoblastic Leukaemia (ALL), accounting for 25 cases (30.8%), followed by neuroblastoma with 13 cases (16%) and retinoblastoma with 1 case (1.2%). Coagulase-negative Staphylococci (CoNS) were isolated in 21 cases (25.9%). Furthermore, 12 (75%) of the Staphylococcus isolates and 12 (57.14%) of the CoNS were found to be methicillin-resistant. Among the gram-negative bacteria, Acinetobacter baumanii showed the highest resistance to the tested antibiotics. Conclusion: The majority of cases were moderately neutropenic, and CoNS was found to be the most common pathogen in BSI. None of the isolates were pan drug-resistant. Empiric antibiotic treatment for FN should be tailored to the locally prevalent pathogens and their susceptibility patterns. This approach will aid in appropriate infection control practices, ultimately reducing mortality and morbidity in affected patients.

565. Antimicrobial susceptibility profiles of Acinetobacter species in blood: 10-year experience from a major United States reference laboratory

Abstract Background Antimicrobial resistance (AMR) is a threat to healthcare, and infections with antimicrobial resistant organisms carry significant morbidity and mortality. Owing to high rates of AMR, the Centers for Disease Control and Prevention listed Acinetobacter baumannii as a top priority pathogen for research and development of new antimicrobial agents. Antimicrobial susceptibility testing is challenging for this organism, and susceptibility profiles are variable, leading to need of a potential guidance document with assistance in selecting effective empiric therapeutic regimens. Methods We retrospectively reviewed the microbiology and antimicrobial susceptibility testing (AST) results for Acinetobacter spp. from blood culture isolates submitted to Mayo Clinic Laboratories from December 2012 to 2022. AST was performed using agar dilution and interpretations following Clinical &amp; Laboratory Standards Institute (CLSI) guidelines. Isolates were identified by MALDI mass spectrometry and/or 16S sequencing, as available (Figure 1).Figure 1:Isolate identification Isolate identification description. Isolates were analyzed based on this classification used in out laboratory. Results 804 blood culture isolates were included. A. baumannii/calcoaceticus complex (27%) was most frequently isolated, followed by A. lwoffii (22%), and showed the highest resistance across all antimicrobials (73% susceptible or below) (Figure 2). A. baumannii/calcoaceticus complex showed rising resistance rates over time from 2012 to 2022 for meropenem, minocycline and ampicillin-sulbactam (Figure 3). Cefiderocol non-susceptible rate was 35% for A. baumannii/calcoaceticus complex.Figure 2:Antimicrobial susceptibility profiles for Acinetobacter spp. Description of susceptibility profiles for Acinetobacter spp. isolates, based on the classification used by our laboratory. Antimicrobials are presented at the top and isolates on the left. Number of isolates analyzed are presented in the table with the percentage of the isolates susceptible to each antibiotic class in parenthesis.Figure 3:Acinetobacter baumannii/calcoaceticus complex isolates and resistance, trend Trend of isolates per year and resistance percentage to meropenem, colistin, minocycline and amp-sulb. Number of isolates per year at the base of each bar; percentage of resistance for antimicrobials expressed on lines. Amp-sulb = ampicillin-sulbactam. Conclusion A. baumannii/calcoaceticus complex showed high levels of resistance ( &amp;gt;75%) across multiple antimicrobials and increasing rates of resistance over time from 2012 to 2022. A high number of cefiderocol non-susceptible organisms is also concerning (Figure 2). Disclosures Audrey N. Schuetz, MD, Merck: Advisor/Consultant

734. Trend Analysis of Oritavancin and Comparator Agents Activity against Enterococcus Causing Infections in US Medical Centers between 2017–2019 and 2022

Abstract Background A new formulation of oritavancin (ORI) to be infused over 1 hour for the treatment of skin and skin structure infections was approved in 2021 by the US FDA. The activity of ORI and its comparators against Enterococcus (ENT) and resistant (R) subsets from US medical centers was evaluated comparatively between 2022 and 2017–2019. Methods 4,462 ENT, including 246/2,556 E. faecalis (EF) from 2022 and 2017–2019, respectively, 148/1,348 E. faecium (EFM), and 14/150 other ENT were collected (1/patient) from 34 US medical centers. Isolates were identified by MALDI-TOF MS and standard microbiology tests and susceptibility (S) tested by CLSI broth microdilution. CLSI clinical breakpoints (BPs) and VanA/VanB phenotypes were used. ORI BPs against vancomycin (VAN)-S EF were applied to all ENT. Results ORI activity against ENT from 2022 (MIC50/90, 0.015/0.03 mg/L) was similar to 2017–2019 (MIC50/90, 0.015/0.06 mg/L; Table). ORI inhibited 97.5%/98.9% of ENT from 2022/2017–2019 at ≤ 0.12 mg/L. VAN and linezolid (LZD) inhibited 97.2%/98.4% and 99.6%/99.6% of ENT from 2022/2017–2019, at the respective BPs. ORI, VAN, LZD and daptomycin (DAP) showed stable S rates ( &amp;gt; 96%) against EF. ORI remained active against 57.1/53.1% of VAN-R EF. VanA rates in VAN-R EF from 2022 and 2017–2019 were 85.7%/93.8%. ORI inhibited the 3 VanB EF isolates at ≤ 0.03 mg/L. LZD and DAP remained active against VAN-R EF (100%). Similar activity was noted for ORI against EFM from 2022 (MIC50/90, 0.008/0.06 mg/L) and 2017–2019 (MIC50/90, 0.008/0.03 mg/L). The EFM S rate to VAN was 35.1% in 2017–2019 and 39.2% in 2022. The S rates to ORI (VAN-S EF BPs) and LZD remained stable ( &amp;gt; 98%) as well as rates of DAP susceptible dose-dependent (SDD; 96.6% in 2022 and 99.5% in 2017–2019). The VanB phenotype increased from 7.8% in 2017–2019 to 20.0% in 2022. ORI inhibited all VanB and 98.5% of VanA EFM at ≤ 0.12 mg/L. LZD inhibited 98.6%/99.4% of VanA EFM isolates in 2022/2017–2022. The DAP SDD rate slightly decreased against VanA EFM (99.7% to 93.1%). ORI and comparators were active against other ENT. Conclusion ORI exhibited potent and stable activity against ENT clinical isolates, including VAN-R EFM in US. An increase in VanB EFM phenotype and a slight decrease in the DAP SDD rates in VAN-R EFM subsets were noted over time. Disclosures Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Entasis: Grant/Research Support|GSK: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Dee Shortridge, PhD, Melinta: Grant/Research Support|Shionogi: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Entasis: Grant/Research Support|Melinta: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support

High frequency of Enterococcus faecalis detected in urinary tract infections in male outpatients – a retrospective, multicenter analysis, Germany 2015 to 2020

BackgroundUrinary tract infections (UTI) in men differ relevantly to women by their pathogens. Gram-positive uropathogens play a relevant role in UTI in men. In this study, we aimed to analyze the epidemiology of Enterococcus faecalis in UTI in male outpatients.MethodsWe conducted a retrospective observational multicenter study during 2015 to 2020 consisting of urine samples of 99,415 adult male outpatients sent from 6,749 outpatient practices from Germany. Proportions were compared using the z-Test and 95% confidence intervals were calculated using the Clopper-Pearson method.ResultsE. faecalis is the 2nd most frequent bacteria (16%) detected in suspected UTI in male outpatients. Young men are predominantly at risk (17%) for isolation of E. faecalis in suspected UTI. In polymicrobial infections E. faecalis is isolated in 47% of all suspected UTI in men. Recurrency of suspected UTI is significantly more frequent when E. faecalis is isolated compared to Escherichia coli (22% vs 26%; p < .001). Recurrency rates of E. faecalis associated UTI increases by age from 12% (18–29 years) to 28% (ge 70 years); p < .001. Congruently the resistance of E. faecalis against ciprofloxacin increases by age from 22% (18–29 years; 2019) to 37% (ge 70 years; 2019); p < .001.ConclusionsE. faecalis is frequently isolated in suspected UTI in male patients. Consequently, Nitrate-sticks results cannot be recommended to exclude UTI in men. The empirical use of ciprofloxacin in young adults can be reasonable. Frequent recurrences in E. faecalis associated suspected UTI emphasizes the importance of microbiological pathogen identification and susceptibility testing in men suffering from UTI.

In-vitro polymicrobial oral biofilm model represents clinical microbial profile and disease progression during implant-related infections.

Clinically relevant in-vitro biofilm models are essential and valuable tools for mechanistically dissecting the etiopathogenesis of infectious diseases and test new antimicrobial therapies. Thus, the aim of this study was to develop and test a clinically relevant in-vitro oral polymicrobial biofilm model that mimics implant-related infections in terms of microbial profile. For this purpose, 24-well plate system was used to model oral biofilms, using three different microbial inoculums to grow in-vitro biofilms: (1) human saliva from periodontally healthy patients; (2) saliva as in inoculum 1+Porphyromonas gingivalis strain; and (3) supra and subgingival biofilm collected from peri-implant sites of patients diagnosed with peri-implantitis. Biofilms were grown to represent the dynamic transition from an aerobic to anaerobic community profile. Subsequently, biofilms were collected after each phase and evaluated for microbiological composition, microbial counts, biofilm biomass, structure, and susceptibility to chlorhexidine (CHX). Results showed higher live cell count (P<.05) for biofilms developed from patients' biofilm inoculum, but biomass volume, dry weight, and microbiological composition were similar among groups (P>.05). Interestingly, according to the checkerboard DNA-DNA hybridization results, the biofilm developed from stimulated human saliva exhibited a microbial composition more similar to the clinical subgingival biofilm of patients with peri-implantitis, with proportions of the main pathogens closer to those found in the disease. In addition, biofilm developed using saliva as inoculum was shown to be susceptible to CHX with significant reduction in bacteria compared with biofilms without exposure to CHX (P<.05). The findings suggested that the in-vitro polymicrobial biofilm developed from human saliva as inoculum is a suitable model and clinically relevant tool for mimicking the microbial composition of implant-related infections.

Refractory Pseudomonas aeruginosa infections treated with phage PASA16: A compassionate use case series

A growing number of compassionate phage therapy cases were reported in the last decade, with a limited number of clinical trials conducted and few unsuccessful clinical trials reported. There is only a little evidence on the role of phages in refractory infections. Our objective here was to present the largest compassionate-use single-organism/phage case series in 16 patients with non-resolving Pseudomonas aeruginosa infections. We summarized clinical phage microbiology susceptibility data, administration protocol, clinical data, and outcomes of all cases treated with PASA16 phage. In all intravenous phage administrations, PASA16 phage was manufactured and provided pro bono by Adaptive Phage Therapeutics. PASA16 was administered intravenously, locally to infection site, or by topical use to 16 patients, with data available for 15 patients, mainly with osteoarticular and foreign-device-associated infections. A few minor side effects were noted, including elevated liver function enzymes and a transient reduction in white blood cell count. Good clinical outcome was documented in 13 out of 15 patients (86.6%). Two clinical failures were reported. The minimum therapy duration was 8days with a once- to twice-daily regimen. PASA16 with antibiotics was found to be relatively successful in patients for whom traditional treatment approaches have failed previously. Such pre-phase-1 cohorts can outline potential clinical protocols and facilitate the design of future trials. The study was funded in part by The Israeli Science Foundation IPMP (ISF_1349/20), Rosetrees Trust (A2232), United States-Israel Binational Science Foundation (2017123), and the Milgrom Family Support Program.