Effective Antibiotics Research Articles

Characteristics and antibiotic resistance patterns of urinary tract isolates in hospitalized and non-hospitalized patients: a cross-sectional study in Khartoum, Sudan

BackgroundUrinary tract infections (UTIs) are widespread worldwide impacting society, economics, and healthcare systems. The rise of antibiotic resistance in both hospital and community settings has further complicated UTI management. This study aims to assess the epidemiologic distribution and microbiologic classification of UTI-causing microorganisms, as well as their resistance patterns.MethodsThis cross-sectional descriptive study was conducted at the National Public Health Laboratories in Khartoum, Sudan. Urine samples were collected from three hospitals from September to December 2021, and 65 bacterial isolates were recovered from patients with clinical symptoms of UTI. Bacterial identification and antimicrobial susceptibility testing were performed using standard bacteriological methods and Kirby-Bauer’s disc diffusion method. Genotyping for Extended Spectrum Beta-Lactamase (EsβL) production was conducted using multiplex PCR.ResultsOf the 65 bacterial isolates, 27 (41.5%) were community-acquired UTI patients (C-UTIs), and 38 (58.5%) were hospital acquired UTI patients (H-UTIs). Males were more commonly affected by H-UTIs (68.4%), while females represented the majority among C-UTIs (85.2%). Gram-negative bacteria were predominant in urinary isolates (81.54%), with Escherichia coli being the most common organism (49.1%). Gram-positive organisms accounted for 18.46% of isolates, with Enterococcus spp. being the most prevalent. In-vitro susceptibility analysis revealed that meropenem was the most effective antibiotic in Gram-negative isolates (77.4%), while nitrofurantoin was the most effective in Gram-positive isolates (91.67%). EsβL production was detected in 11/23 (47.8%) of the tested isolates with Escherichia coli being the most common ESβL producer.ConclusionThis study highlights the pattern of antibiotic-resistant bacteria in UTIs and their significance. Continuous monitoring, development of local antibiograms, and implementation of surveillance programs are essential for guiding empirical antibiotic use and managing UTIs effectively, especially in resource-limited settings like Sudan.

Asymptomatic nasopharyngeal carriage of multidrug resistant bacteria among children at University of Gondar Hospital Northwest Ethiopia Revealing Hidden Health Risks

Gram-negative bacteria in the nasopharynx can eventually invade bacteria-limited sites and cause serious illnesses such as meningitis, otitis media, and pneumonia. However, data related to the carriage of these bacteria in children attending outpatient departments in the study area are limited. To assess nasopharyngeal carriage, antibiotic susceptibility patterns, and associated factors of gram-negative bacteria among children attending the outpatient department at the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia. A hospital-based cross-sectional study was conducted from September 1, 2023, to December 30, 2023. A total of 385 children aged 3 to 14 years were enrolled using a systematic random sampling technique. Sociodemographic and clinical data were collected using a semistructured questionnaire. A total of 385 nasopharyngeal samples were collected using a sterile specimen collection nasopharyngeal swab, transported using Amie’s transport medium, and subsequently inoculated on chocolate agar, blood agar, modified thayer martin agar, and MacConkey agar plates. Bacterial species were identified by colony morphology, Gram staining, and biochemical tests such as oxidase tests, satellitism tests, and carbohydrate utilization tests. An antibiotic susceptibility test was performed using the Kirby–Bauer and modified Kirby–Bauer methods on Mueller–Hinton agar plates. The data were entered into Epi-Data version 4.6.0.6 and exported to SPSS version 25 for analysis. The adjusted odds ratio at a 95% confidence interval with a P value of < 0.05 in the binary logistic regression model was considered to indicate statistical significance. The overall nasopharyngeal carriage of gram-negative bacteria was 146 (37.9%) (95% CI: 33.2–42.9). Among these, nonfastidious gram-negative bacteria represented 45 (11.7%), followed by M. catarrhalis 41 (10.6%), N. meningitidis 34 (8.8%), and H. influenzae 26 (6.8%). The isolates exhibited high resistance to tetracycline (85; 75.9%), trimethoprim-sulfamethoxazole (105; 71.9%), ampicillin (76; 67.9%), and amoxicillin/clavulanic acid (60; 69.8%) but high susceptibility to meropenem (122; 83.6%), gentamicin (73; 84.9%), and minocycline (87; 72.5%). There were 99 total multidrug-resistant strains (67.8%, 95% CI: 59.7–75.0). Male sex (AOR = 1.785, 95% CI: 1.102–2.892, P = 0.019), smoking (AOR = 2.675, 95% CI: 1.149–6.230, P = 0.022), and large family size (≥ 5) (AOR = 1.857, 95% CI: 1.140–3.023, P = 0.013) were risk factors for nasopharyngeal colonization. Increased nasopharyngeal colonization of multidrug-resistant gram-negative isolates was observed in this study. Gentamicin, minocycline, and meropenem were the most effective antibiotics for the tested isolates. Bacterial colonization increased with increasing family size, smoking status, and male sex. Therefore, a definitive diagnosis in the outpatient pediatric department should be based on culture and susceptibility test results.

Clinical and microbiological profile of patients with urinary tract infection visiting general outpatient department, National Referral Hospital

Background: Urinary Tract Infection (UTI) is one of the most common infections encountered in outpatient settings. The random use of antibiotics, particularly in resource-limited settings, has contributed to the emergence of antibiotic resistance. This study aimed to identify common uropathogens and assess their antibiotic sensitivity patterns among patients with symptoms of UTI attending the General Outpatient Department (GOPD) at Jigme Dorji Wangchuck National Referral Hospital in Thimphu. Method: A cross-sectional study was conducted from September 2021 to August 2022, involving patients over the age of 13 years with symptoms of UTI. Midstream urine collected via proper technique was analyzed by the laboratory. Once there was growth on the urine culture media, antibiotic sensitivity testing was performed against the commonly used antibiotics in the GOPD. Result: Amongst 351 participants, 77.8% were female, and the most common symptoms reported were dysuria (93.4%) and increased urinary frequency of micturition (92.3%). Patient’s age, sex and previous episodes of UTI were significantly associated with the occurrence of UTI (p &lt; 0.05). The overall urine culture positivity rate was 50.53%, with Escherichia coli (84.7%) identified as the predominant uropathogen, followed by Klebsiella pneumoniae (7.3%). Among the antibiotics tested, gentamicin and nitrofurantoin exhibited the highest sensitivity, while amoxicillin and ampicillin were the least effective antibiotics against Escherichia coli. Conclusion: UTI predominantly affected females. Escherichia coli was the commonest causative agent and nitrofurantoin could be the potential drug of choice for UTI treatment. The irrational use of antibiotics, as a contributing factor to resistance should be addressed.

The Hidden Threat of Antimicrobial Resistance: A Case Study from A Private Hospital in Jordan

Antibiotic resistance is considered a widespread problem with global health implications, leading to increased patient morbidity and impacting the selection of effective antibiotics, consequently influencing patient recovery. This study aimed to assess antibiogram resistance patterns of bacterial records at the Islamic Hospital in Jordan using a retrospective study during the period 2020-2022. A total of 9369 samples obtained from different patients were cultured. Data were processed and analyzed with SPSS v.23.0. The results showed that 2841 (30.3%) samples were positive for bacterial infections. Microbial profiles of positive samples indicated the highest proportion for Escherichia coli, 39%, followed by Klebsiella pneumoniae 12% were the most frequent Gram-negative bacterial isolates, whereas Staphylococcus aureus 13% and Streptococcus pneumoniae 4% were the most common Gram-positive bacterial isolates. Interestingly, multidrug-resistant bacteria comprised 61.7% of the isolates. The percentage of multi-drug resistance in isolates of Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae was 68.7%, 73.1%, and 72%, respectively. Escherichia coli was most resistant to ampicillin (89%) and most sensitive to imipenem (100%). Klebsiella pneumoniae showed a 100% sensitivity to meropenem but 49% resistance to ceftriaxone. Pseudomonas aeruginosa was the most sensitive to amikacin and colistin (86% and 100%, respectively). Staphylococcus aureus isolates have resistance rates of 78% for ciprofloxacin, 35.6% for clindamycin and an overall resistance rate of 68.7%. These findings indicate multiple resistance for isolated bacteria. Therefore, antimicrobial resistance should be monitored continuously, and patients should be treated based on anti-microbial susceptibility tests.

Isolation and Identification of Pathogenic Bacteria from Urinary Tract Infection in Patients Attending Rwanda Military Hospital

Background: About 150 million people worldwide are diagnosed with urinary tract infection every year and more than half of women will get at least one in their lifetimes. Overuse and misuse of antibiotics have contributed to the growing problem of resistance amongst uropathogenic bacteria making it hard to treat UTIs. There is an increasing prevalence of antibiotic resistance and that’s why area-specific monitoring studies to document the microorganisms causing UTIs and their antimicrobial susceptibility is mandatory for helping the selection of an effective empirical treatment. Aim: The present study aimed to determine bacteria causing UTIs and their antibiotic susceptibility patterns among patients attending Rwanda military hospital. Methodology: The study was a cross-sectional study and a total number of 118 patient’s urine samples were tested in microbiology Lab. Results: Most frequently isolated bacteria to cause UTIs in this study was E. coli (59%) followed by Klebsiella pneumonia (16%), S. aureus (6%), Citrobacter freundii (5%), Proteus spp. (3%), S. Saprophyticus (3%), Streptococcus spp. (3%), Pseudomonas aeruginosa (2%), Klebsiella oxytosa (2%) and Acinetobacter baumanii (2%). Meropem, imipem, gentamicin and cefotaxime were the most effective antibiotics in susceptibility testing. Thus, ciprofloxacin, sulfamethoxazole and norfloxacin were mostly developed resistance to isolated bacteria. Conclusion: The study recommended that the ministry of health in Rwanda should establish the commission or government body which will be in charge of controlling use of antibiotics properly and fighting against drugs resistance in Rwanda. Keywords: Pathogenic bacteria, Urinary tract infections, E.coli, Antibiotics

HPB SO02 - Cutting surgical site infection rates in perihilar cholangiocarcinoma with informed changes to perioperative antibiotic prophylaxis: A quality improvement project in a UK hepatopancreatobiliary tertiary centre

Abstract Background Perihilar cholangiocarcinoma (pCCA) is the most common cancer of biliary epithelia. While potentially curative, surgical resection is associated with high morbidity and mortality. Surgical site infections (SSIs) are common and pernicious. Preoperative biliary instrumentation is universal: to confirm histological diagnosis and deploy stents to relieve jaundice. Patients receive multiple antibiotic courses as periprocedural prophylaxis and to treat cholangitis. They are at high risk of harbouring bacteria not quelled by perioperative prophylactic antibiotics given for other general surgical procedures. Studying the biliary microbiome, this quality improvement project sought to reduce SSIs through informed changes to local guidelines on perioperative antibiotic prophylaxis. Method Health records of all patients undergoing resection for pCCA in a UK hepatopancreatobiliary centre from February 2009 to January 2024 were analysed retrospectively (n=118). For all patients, we routinely sent intraoperative bile swabs for culture and sensitivity. Informed by these microbiology results, multidisciplinary discussion led to changes to local guidelines in March 2019. Formerly, cefuroxime and metronidazole were given on anaesthetic induction, with subsequent antibiotic choice and duration according to surgeon preference. New guidance stipulated teicoplanin and piperacillin/tazobactam be given on induction and for 72 hours postoperatively. We studied the impact of these changes on SSIs within 30 days. Results 75 patients received cefuroxime and metronidazole; 43 patients were given teicoplanin and piperacillin/tazobactam after the policy change. Proportions of patients who developed any SSI substantially fell following the guideline change (55% v 28%; p=0.0049), primarily owing to reductions in intraperitoneal collections (39% v 21%; p=0.047). Rates of deep (8% v 2%; p=0.21) and superficial incisional infections (8% v 5%; p=0.49) were not significantly affected. Associated secondary outcomes were drops in post-hepatectomy liver failure (17% v 5%; p=0.047), and 90-day mortality (16% v 5%; p=0.067), albeit the latter was not statistically significant. Conclusion Invasive investigative work-up, disease complications and exposure to multiple courses of antibiotics prior to resection of pCCA subject patients’ biliary systems to colonisation with antimicrobial-resistant bacteria. We urge centres that undertake these operations to introduce intraoperative bile cultures as a part of routine practice to inform local guidance on perioperative antimicrobial prophylaxis. We demonstrated effective antibiotics in the perioperative period can have enormous benefits to patient outcomes.

Unique T cell signatures associated with reduced Chlamydia trachomatis reinfection in a highly exposed cohort.

Chlamydia trachomatis (CT) is the most common bacterial sexually transmitted infection (STI) in the United States, despite effective antibiotics. Information regarding natural immunity to CT will inform vaccine design. The objectives of this study were to determine immune cell populations and functional features associated with reduced risk of CT reinfection or endometrial CT infection. PBMCs were collected from a cohort of CT-exposed women who were tested for CT and other STIs at the cervix and endometrium (to determine ascension) and were repeatedly tested over the course of a year (to determine reinfection). Mass cytometry identified major immune populations and T cell subsets. Women with CT had increased CD4+ effector memory T cells (TEM) compared to uninfected women. Specifically, Th2, Th17, and Th17 DN CD4+ TEM were increased. Th17 and Th17 DN CD4+ central memory T cells (TCM) were increased in women who did not experience follow-up CT infection, suggesting that these cells may be important for protection. These data indicate that peripheral T cells display distinct features that correlate with natural immunity to CT and suggest that the highly plastic Th17 lineage plays a role in protection against reinfection.

Investigating the Prevalence of Bacterial Infections in Patients with Coronavirus Disease 2019 Hospitalized in Intensive Care Unit and Determining their Antibiotic Resistance Patterns.

COVID-19 patient hospitalization, particularly in intensive care units, exposes them to bacterial and fungi co-infections, which can have very serious consequences, including increased mortality. In addition, antibiotic resistance among pathogens is a hidden threat behind COVID-19. In the period from 2020 September to 2021 August, bacterial isolates from COVID-19 patients admitted to the ICU of Sina Hospital in Hamadan, Iran, were collected and identified based on standard biochemical tests. COVID-19 cases were confirmed based on clinical symptoms, computed tomography, and polymerase chain reaction. Antimicrobial susceptibility tests were conducted using disc diffusion and broth microdilution methods. In total, 207 bacterial isolates were collected, with Klebsiella pneumoniae account-ing for 69 (33.33%) and Acinetobacter baumannii accounting for 59 (28.15%). The frequency and percentage of isolated bacteria were as follows: Alcaligenes species 28 (13.59%), Staphylococcus aureus 18 (8.73%), Pseudomonas aeruginosa 15 (7.28%), Escherichia coli 11 (5.33%), Stenotrophomonas maltophilia 3 (1.45%), Enterococcus species 3 (1.45%), and Serratia species 1 (0.48%). About 95.38% resistance to ceftazidime and cefotaxime and 92.31% resistance to ciprofloxacin and cefepime were found in K. pneumoniae isolates. A. baumannii isolates were 100% resistant to cefotaxime, ceftriaxone, and cefepime. About 22.22% resistance to vancomycin and 66.67% resistance to clindamycin, erythromycin, and cefoxitin were seen in S. aureus isolates. Knowledge of bacterial co-infections and their antibiotic resistance pattern in COVID-19 patients can help in choosing effective antibiotics for the treatment and prevention of antibiotic resistance.

Overexpression of β-lactamase genes (blaKPC, blaSHV) and novel CirA deficiencies contribute to decreased cefiderocol susceptibility in carbapenem-resistant Klebsiella pneumoniae before its approval in China.

Cefiderocol (FDC) is an effective antibiotic that is used to treat severe infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). The mechanisms underlying FDC resistance and molecular epidemiology in China remain unclear. We collected 477 non-duplicate CRKP clinical isolates in central China and characterized their susceptibility to FDC, virulence genes, and sequence typing. The overall FDC susceptibility rate of CRKP was 99.2% in central China, which was higher than that in North America and Europe (96.1%), with MIC50/90 values of 1/2 mg/L. The decrease in FDC susceptibility in central China was concentrated in the ST11 CRKP-carrying virulence plasmids. Whole-genome sequencing (WGS) and quantitative reverse transcription PCR (qRT-PCR) experiments showed that serine β-lactamases, especially highly expressed KPC and SHV, substantially decreased FDC susceptibility in four FDC non-susceptible isolates (two resistant and two intermediate isolates). Notably, different CirA deficiencies, p.E450GfsTer16 and p.E133Ter, were found in both of the resistant isolates. In contrast, global WGS data indicate that the resistance mechanisms in North America and Europe were primarily associated with NDM and KPC variants, predominantly found in ST307 and ST147. Overall, FDC exhibits excellent activity against CRKP in central China, with resistance mechanisms primarily related to high KPC and SHV expression, along with deficiencies in CirA, frequently observed in ST11. This is remarkably different from the situation in North America and Europe and will directly impact the choice of clinical interventions. Additionally, the surveillance of FDC resistance in China is imperative.

Prevalence of Vancomycin-Resistant Enterococcus spp. Isolates in Southeast Iran, Zahedan

Background: Enterococci are clinically significant, especially in individuals with compromised immune systems, which are recognized as a critical contributor to nosocomial infections. Objectives: This study aimed to determine antibiotic susceptibility profiles and vancomycin-resistance Enterococcus (VRE) isolates in Zahedan, Iran. Methods: A hospital-based cross-sectional study was conducted at Ali Ibne Abi Talib Hospital from March 2019 to February 2022. Clinical samples included urine, blood, abscesses and other body fluids from patients referred to this hospital during the study period. A total of 3000 patients were included in the study, and the Kirby-Bauer method was used to test isolates identified by morphological and biochemical characteristics for antibiotic susceptibility. Data were analyzed using SPSS software version 20. P-values &lt; 0.05 were considered statistically significant. Results: Out of 3000 culture-positive clinical samples comprised of 82 urine, ten blood, one tracheal, two wound, and one pulmonary isolate, were identified as Enterococcus faecalis (69.1%), Enterococcus faecium (7.3%), and Enterococcus spp. (23.6%). Moreover, two-thirds of isolates were multidrug-resistant (MDR). Although 66.7% and 63.9% were sensitive to nitrofurantoin and linezolid, resistance to ciprofloxacin (74.2%) and ampicillin (65.9%) was frequently observed. Nitrofurantoin or linezolid were the only effective antibiotics for UTIs. In addition, 50% of isolates were resistant to vancomycin. Conclusions: Based on the results, a combination of vancomycin/or linezolid and nitrofurantoin for urine infections was effective against Enterococci in this clinical center. Nevertheless, continuous and frequent surveillance for resistance patterns is necessary for the reasonable and evidence-based use of antibiotics.

In silico discovery of druggable targets in Citrobacter koseri using echinoderm metabolites and molecular dynamics simulation

Citrobacter koseri causes infection in people who are immunocompromised. Without effective antibiotics, these infections can become severe and life-threatening, so effective drugs are essential to treat these infections. Utilizing subtractive genomics, 2699 ORFs were predicted and translated into amino acid sequences. Metabolic pathway analysis and subcellular localization helped define the roles of key bacterial proteins. Two druggable proteins, WP_012000829.1 and WP_275157394.1, were discovered as promising targets. Alpha Fold provided 3D structures, and a library of 1600 echinoderm metabolites was docked against these proteins, with Ampicillin, Levofloxacin, and Doxycycline as controls. Notably, CMNPD13085 and CMNPD15632 exhibited the highest binding affinities for WP_012000829.1 and WP_275157394.1, respectively. Molecular dynamics simulations and MM-GBSA binding free energy complemented docking results. However, acknowledging the reliance on computational validations, the study emphasizes the need for essential in-vitro research to transform these potential inhibitors into therapeutic drugs.

What role does antibiotic resistance play in secondary endodontic infections?

The systematic review utilised multiple electronic databases to gather relevant literature, including PubMed, Scopus, EMBASE, Web of Science, and Medline. The search was conducted focusing on clinical studies where Enterococcus strains were isolated to assess their antimicrobial resistance. The search strategy was designed based on the PICO model, targeting patients with secondary/persistent endodontic infections (SPEI) and evaluating the resistance profiles of Enterococci to systemic antibiotics. A total of 584 studies were initially identified through database searches. After removing duplicates, 517 studies were excluded based on title and abstract screening, leading to the final inclusion of 11 clinical trials that met the eligibility criteria. The studies were conducted in various countries, including Brazil, Lithuania, Poland, Germany, Sweden, the United States, and Japan. The focus was on permanent teeth with post-treatment apical periodontitis undergoing endodontic retreatment. Data extraction was performed independently by two reviewers, who compiled details such as authorship, year of publication, country of study, sample groups, bacterial strains tested, antibiotics used, and resistance outcomes. The risk of bias was assessed using the ROB-2 platform, and all studies were considered to have a low risk of bias, with occasional minor deficiencies noted. The analysis revealed fluctuating resistance profiles of Enterococcus faecalis (E. faecalis) and Enterococcus faecium (E. faecium) to various antibiotics over time. E. faecalis isolated from teeth with SPEI showed intermediate resistance to 16 antibiotics. The most effective antibiotics identified were the combination of amoxicillin and clavulanate, followed by amoxicillin and benzylpenicillin. In patients with penicillin allergies, moxifloxacin and azithromycin were suggested as alternatives, albeit with caution due to their varying resistance levels. The antibiotics demonstrating the highest resistance patterns against E. faecalis included clindamycin, gentamicin, metronidazole, and rifampicin, which are contraindicated in SPEI cases. Ongoing monitoring of antibiotic resistance patterns is crucial for effective endodontic treatment protocols. The emergence of resistance among Enterococci, particularly E. faecalis, necessitates regular susceptibility testing to inform clinical decisions and improve treatment outcomes. The findings underscore the need for health professionals to stay informed about the evolving resistance landscape to ensure safe and effective therapeutic regimens in endodontics.

064. Overview of Bacterial Patterns and Antibiotic Resistance on Cholangitis Patients at Hasan Sadikin General Hospital from January to December 2023

Background: Cholangitis is a serious infection of the bile ducts that requires prompt treatment, often with antibiotic therapy. Although antibiotic use, especially ceftriaxone and metronidazole, is vital in treatment, antibiotic resistance remains a significant challenge. Unfortunately, data on bacterial resistance patterns in cholangitis patients treated at Doctor Hasan Sadikin Hospital in Bandung is still limited. This study aims to describe the bacterial patterns and antibiotic resistance in cholangitis patients at Doctor Hasan Sadikin General Hospital. Another objective is to assess the effectiveness of ceftriaxone and metronidazole therapy in patients with moderate to severe cholangitis. Methods: This research employed a retrospective descriptive design by collecting data from the medical records of acute cholangitis patients treated at Doctor Hasan Sadikin General Hospital from January to December 2023. A total of 126 patient samples meeting the inclusion criteria were analyzed through blood cultures, and sensitivity tests were conducted against various antibiotics. Data were analyzed using SPSS software. Results: The results showed that Escherichia coli (26.3%) was the most commonly found bacterium, followed by Staphylococcus haemolyticus and Klebsiella pneumoniae (each at 13.2%). The highest resistance was observed against ampicillin (78.9%), while the most effective antibiotic was tigecycline (92.1% sensitivity). Conclusion: In conclusion, ceftriaxone and metronidazole as empiric therapy remains effective for most cholangitis patients, although resistance to certain antibiotics like ampicillin warrants attention. This study highlights the importance of regular monitoring of antibiotic resistance patterns to ensure proper treatment and reduce morbidity and mortality rates among cholangitis patients.

The effectiveness of the HB&amp;L system in bacteriuria determining

Urinary tract infections (UTIs) are characterized by high prevalence in various populations, recurrent course, complications and accumulation of antibiotic resistant strains. Researchers continue to search for objective criteria for the laboratory diagnosis of associated diseases, including methods for determining bacteriuria The implementation of anautomatic bacteriological analyzer into the laboratory practice would make possible to organize screening studies of UTIs with high sensitivity and specificity, in parallel with studies of the resistant phenotypes’prevalence. This will help to create the basis for the development of highly effective and reasonable antibiotic therapy, and, in general, to improve the epidemiological situation associated with these infections.

OPTIMIZING DRUG DOSING IN CRITICALLY ILL PATIENTS WITH AUGMENTED RENAL CLEARANCE: A COMPREHENSIVE REVIEW AND META-ANALYSIS

Renal clearance plays a pivotal role in eliminating most administered drugs, particularly antibiotics, which is crucial for achieving therapeutic goals by maintaining plasma concentrations within the therapeutic window. Various pre-existing conditions such as renal replacement therapies, kidney or liver impairment, and enhanced excretory organ function can disrupt drug concentrations, leading to treatment failure. Augmented Renal Clearance (ARC) exacerbates this by causing rapid drug elimination, notably in critically ill patients. Consequently, careful monitoring and adjustment of drug dosages tailored to individual patient conditions and comorbidities are imperative to prevent sub-therapeutic outcomes or treatment failures. Our review highlights the necessity of dosage modifications informed by current research to optimize therapeutic outcomes in such cases. We provide a comprehensive table detailing effective antibiotics and their adjustments for ARC.

Bacterial Co-Infections and Antibiotic Resistance in Urinary Tract Infection of Covid-19 Patients in Erbil City

The COVID-19 pandemic has raised concerns over secondary infections because it has limited treatment options and empiric antimicrobial treatment poses serious risks of aggravating antimicrobial resistance. Many studies have shown that COVID-19 patients are predisposed to developing secondary infections. The prevalence of urinary tract infections (UTI) was evaluated in 248 patients admitted to different hospitals in Erbil city, Iraq. Results showed 138 (55.65%) patients were positive for bacterial growth, of which 72 isolates of Gram-negative and 66 isolates of Gram-positive bacteria were isolated and identified from the urine of COVID-19 patients depending on the 16S rRNA gene using PCR. The predominant obtained bacteria were Staphylococci species, of which isolates belong to 6 species, and the predominant Gram-negative species was Pseudomonas spp. which belongs to 4 species. Also, their susceptibility to 15 antibiotics was tested and it was found that most of the Gram-negative isolates were highly resistant to ampicillin 66(91.66%), amoxicillin 60(83.33%), cephalexin 52(72.22%) and cefixime 50(69.44%). While the most effective antibiotic was imipenem, and with percentage of 26(36.11%), it also showed variable sensitivity to other antibiotics. For Gram-positive bacteria, the highest resistance was against cefixime 40(60.60%), ampicillin 28(42.42%), and 18(27.27%) for both amoxicillin and ciprofloxacin, while the most effective antibiotic was gentamicin, which showed effectiveness against all the Gram-positive isolates. Another part of the study concerned with detection of the existence of ESBLs genes responsible for antibiotic resistance. The results revealed that all the isolates possessed the 16S rRNA gene, whereas blaTEM and blaCTX-M were found to be the most possessed genes in all the isolates, with a percentage of (88.33%).

Immunomodulatory activity of omadacycline in vitro and in a murine model of acute lung injury.

Cystic fibrosis (CF) is characterized by chronic airway obstruction, infection, and inflammation leading to progressive loss of lung function and eventual respiratory failure. Omadacycline, a tetracycline antibiotic, demonstrates in vitro activity against key CF pathogens, substantial lung penetration, and increasing clinical evidence for the treatment of lung infections in people with CF (PwCF). Preliminary in vitro data demonstrate that omadacycline exhibits anti-inflammatory activity. This study aims to determine the anti-inflammatory effects of omadacycline in vitro and in a murine model of lipopolysaccharide (LPS)-induced lung neutrophilia. In vitro, THP-1-derived macrophages were treated with omadacycline (20-100 µg/mL) 30 minutes prior to LPS stimulation. Pro-inflammatory cytokine (TNF-α, IL-1β/6), chemokine (CXCL-1/2), and MMP-9 levels were analyzed after 24 hours by ELISA. Omadacycline's effects on IL-8-induced human neutrophil chemotaxis were also investigated. In vivo, omadacycline (2.5-30 mg/kg), comparators dexamethasone (1 mg/kg), and azithromycin (30 mg/kg) were administered 1 hour before and 6 hours after intranasal LPS challenge, respectively. Leukocyte counts and differentials in bronchoalveolar lavage fluid (BALF), inflammatory mediator levels in BALF and lung homogenates, pulmonary edema markers, and the severity of lung injury were evaluated 24 hours or 48 hours post-challenge. Treatment with omadacycline in vitro resulted in significant, dose-dependent reductions in IL-6, CXCL-1, and MMP-9 expression and inhibition of IL-8-induced neutrophil chemotaxis. In vivo, omadacycline yielded protective and therapeutic effects by reducing the production of proinflammatory cytokines and chemokines and neutrophil infiltration into the lungs, along with modestly improving lung injury severity. These preclinical results suggest that omadacycline may provide dual anti-bacterial and anti-inflammatory activities relevant to chronic lung infection treatment in PwCF.IMPORTANCENontuberculous mycobacteria, particularly Mycobacterium abscessus complex (MABSC), are a major concern for people with cystic fibrosis (PwCF) due to their association with deteriorating lung function. A substantial barrier to effective treatment is the limited number of safe and effective antibiotics. Omadacycline offers a potential advancement in managing MABSC infections in cystic fibrosis due to its activity, effective penetration into pulmonary secretions, improved tolerability, and good oral bioavailability as shown in healthy volunteers. Our study is the first to explore omadacycline's effects in a model of sterile lung inflammation and acute lung injury. We found that omadacycline not only has potent anti-bacterial properties but also exhibits anti-inflammatory effects, reducing lung inflammation and injury in our preclinical models. These findings underscore omadacycline's potential as a dual-action therapy for lung infections in PwCF, indicating significant potential to improve patient outcomes and guide more effective antimicrobial therapy decisions.

Antimicrobial and Anti-quorum Sensing Activity of Geranium sp.

Aim: Antibiotic resistance, which has increased rapidly in recent years, is one of the leading public health threats. Alternative methods are being investigated for effective antibiotics in the fight against resistance. Geranium species are widely used for constipation, digestive disorders, and diabetes. It is also known that the plant is used in various public health applications. In line with this information, it was aimed to investigate the antimicrobial and anti-quorum sensing properties of the Geranium sp. Material and Methods: In this study it was aimed to prepare methanol, ethyl acetate, ethanol, and hexane extracts of Geranium sp. flower parts belonging to Rize province and investigate their antimicrobial activities by agar well diffusion method against various Gram-negative and Gram-positive bacteria and two fungal species. Anti-quorum sensing activity was determined using Chromobacterium violaceum strain. Results: Methanol extract of Geranium sp. showed antimicrobial activity against seven species whereas extraction with ethyl acetate showed antimicrobial activity against eight species. The ethanol extracted samples have the lowest antimicrobial activity so that only six species were affected. Additionally, methanol extract of Geranium sp. had violacein inhibition activity. Conclusions: As a result, it was determined that the plant, especially its methanol extract, has antimicrobial and anti-quorum sensing properties.

Isolation and antibiogram of some bacterial isolates from patients with ear infection in a tertiary health care facility at Benin City, Edo State, Nigeria

Ear infection has been reported as a common health concern globally, impacting individuals across diverse demographic factors. Causative bacterial agents of this infection are constantly changing and require continuous surveillance to monitor emerging trends. This study investigated the bacterial etiologic agents and their susceptibility patterns among patients with ear infection at the study Centre. A total of 43 patients who visited the Ear, Nose and Throat clinic of the University of Benin Teaching Hospital that were diagnosed with ear infection were evaluated. Patient data and specimen were collected after which isolated bacteria were subjected to antimicrobial susceptibility testing against some antibiotics (Sparfloxacin, Azythromycin Amoxicillin-clavulanic acid and amoxicillin) using standard methods. Results obtained showed that patients aged 16-25 years were more predisposed to ear infection and substantial number of them (60.5%) reported previous history of the infection. Staphylococcus (48.70%) and Pseudomonas (26.30%) were the most predominant bacterial isolated from these patients. Other isolates included; Bacillus (14.5%), Corynebacterium (3.90%), Enterobacterium (1.30%), and Klebsiella (3.9%). Antibiogram revealed that 78.9% of the isolates were susceptible to the killing effects of Azithromycin and only 39.3% were susceptible to amoxicillin. However. 69.8% of isolates were susceptible to amoxicillin- clavulanic acid combination therapy. Conclusively, Staphylococcus and Pseudomonas, were the leading cause of ear infection at the study center. Azithromycin as well as amoxicillin- clavulanic acid combination were the most effective antibiotics against the encountered bacterial isolates and these antibiotics can be used as a first line drug in the management of ear infection at the study.

Mechanisms of Staphylococcus aureus survival of trimethoprim-sulfamethoxazole-induced thymineless death.

Trimethoprim-sulfamethoxazole (SXT) is commonly used to treat diverse Staphylococcus aureus infections, including those associated with cystic fibrosis (CF) pulmonary disease. Studies with Escherichia coli found that SXT impairs tetrahydrofolate production, leading to DNA damage, stress response induction, and accumulation of reactive oxygen species (ROS) in a process known as thymineless death (TLD). TLD survival can occur through the uptake of exogenous thymidine, countering the effects of SXT; however, a growing body of research has implicated central metabolism as another potentially important determinant of bacterial survival of SXT and other antibiotics. Here, we conducted studies to better understand the mechanisms of TLD survival in S. aureus. We found that thymidine abundances in CF sputum were insufficient to prevent TLD of S. aureus, highlighting the importance of alternative survival mechanisms in vivo. In S. aureus cultured in vitro with SXT and low thymidine, we frequently identified adaptive mutations in genes encoding carbohydrate, nucleotide, and amino acid metabolism, supporting reduced metabolism as a common survival mechanism. Although intracellular ROS levels rose with SXT treatment in vitro, survival was not improved in the presence of ROS scavengers, unlike in E. coli. SXT challenge induced the SOS response, which was alleviated by added thymidine. Finally, an inactivating mutation in the phosphotransferase gene ptsI conferred both limitation in cellular ATP and improved survival against TLD. Collectively, these results suggest that alterations in core metabolic functions, particularly those that reduce ATP levels, predominantly confer S. aureus survival and persistence during SXT treatment, potentially identifying novel targets for co-treatment.IMPORTANCEStaphylococcus aureus is a ubiquitous organism and one of the leading causes of human infections, many of which are difficult to treat due to persistence, antibiotic resistance, or antibiotic tolerance. As our arsenal of effective antibiotics dwindles, the need for improved treatments becomes increasingly urgent, necessitating a better understanding of the precise mechanisms by which pathogens evade our most critical antimicrobial agents. Here, we report a systematic characterization of the mechanisms of S. aureus survival to treatment with the first-line antistaphylococcal antibiotic trimethoprim-sulfamethoxazole, identifying pathways and candidate targets for enhancing the efficacy of available antimicrobial agents.