Empirical Therapy Research Articles

How Would You Manage This Patient With Gastroesophageal Reflux Symptoms? Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Gastroesophageal reflux disease (GERD) is a common medical condition presenting with heartburn, regurgitation, cough, hoarseness, and/or wheezing. Patients with classic GERD symptoms often do not require diagnostic studies before empirical treatment is initiated. However, if atypical features are present, including alarm symptoms for malignancy, or if symptoms do not respond to conventional treatment, upper endoscopy may be necessary. The optimal management of GERD, which is the subject of debate, depends on the frequency and severity of symptoms. In 2021, the American College of Gastroenterology published updated recommendations for diagnosis and management of GERD. In addition to histamine-2 receptor antagonist or proton-pump inhibitor therapy, which may be prescribed as needed or continuously, lifestyle and dietary modification are often advised. Here, 2 physicians, a primary care practitioner and a gastroenterologist, debate how to manage a patient with GERD symptoms. They discuss the diagnosis of this condition, its initial management, indications for upper endoscopy, and how to care for the patient whose condition does not respond to empirical therapy.

Management of endometriosis: a call to multidisciplinary approach.

Endometriosis is defined as the presence of endometrial-like glands and stroma outside of the uterus. There are three types of endometriotic lesions: superficial or peritoneal endometriosis, ovarian endometrioma, and deep infiltrating disease. Endometriosis not only occurs in the pelvis but also can be found in extrapelvic sites such as the gastrointestinal tract, upper abdominal viscera, genitourinary tract, abdominal wall, diaphragm, and thoracic cavity. After thorough history and physical examination is performed, imaging, such as ultrasound or magnetic resonance imaging (MRI), should be obtained if there is high suspicion for deep-infiltrating endometriosis to better assess visceral involvement. Endometriosis can be suspected based on symptoms, physical examination findings, and imaging. However, a definitive diagnosis requires histopathologic confirmation. Treatment options include expectant, medical, and surgical management. Endometriosis is largely a quality-of-life issue, and treatment should be tailored accordingly with empiric medical therapy frequently utilized. Medical management focuses on symptom improvement. Surgical management with excision of endometriosis is preferred over ablation or fulguration of endometriotic lesions. In the case of deep or extrapelvic endometriosis, treatment with a multidisciplinary team with experience in the treatment of advanced-stage endometriosis is essential to minimizing morbidity and increasing long-term success.

Case report: diagnosis of neurobrucellosis in a non-endemic area child using metagenomic next-generation sequencing.

Brucellosis with neurological symptoms at onset is rare in children and is frequently misdiagnosed or overlooked due to nonspecific clinical presentations, particularly in non-endemic areas. We report a case of neurobrucellosis in a child from a non-pastoral area, diagnosed via metagenomic next-generation sequencing (mNGS). The patient presented with headache and altered consciousness, accompanied by fever, projectile vomiting, seizures, and urinary incontinence. Physical examination indicated possible nuchal rigidity. Cerebrospinal fluid (CSF) analysis showed colorless and clear fluid, with a white blood cell count of 259 × 10⁶/L, 4.6% polymorphonuclear cells, positive protein qualitative test, protein level of 0.78g/L, and glucose level of 1.66 mmol/L. Initial diagnosis suggested central nervous system infection, and empirical treatment led to improvement in consciousness. However, after a few days of stable body temperature, the patient experienced recurrent fever. Ultimately, mNGS of CSF identified Brucella melitensis, confirming neurobrucellosis. Following treatment with ceftriaxone, doxycycline, and rifampin, the patient's clinical symptoms improved significantly, and follow-up CSF analysis showed normalization of cell counts. This case highlights the early diagnostic utility of mNGS in CSF for neurobrucellosis and its role in differential diagnosis.

Empiric gram-negative antibiotics usage among critically ill patients across 13 ICUs of Nepal: A retrospective cohort study

Background This study aims to investigate the associations between patient characteristics and the receipt of empiric broad-spectrum gram-negative antimicrobials among adult patients admitted to ICUs in Nepal. Methods A retrospective cohort study was conducted in 13 ICUs in Nepal between January 1st, 2020, and December 31st, 2022. Empiric antibiotic use was defined as receiving gram-negative antibiotics within the first two days of ICU admission without evidence of infection from culture. Patient characteristics between patients receiving narrow-spectrum antibiotics and broad-spectrum gram-negative antibiotics were compared. Continuous variables were compared using mean and standard deviation, with mean differences and 95% confidence intervals calculated. Categorical variables were compared using the chi-square test. A multi-level multivariable regression model assessed the relationship between selected variables and broad-spectrum antibiotic usage, treating admitting ICU as a random factor. Results Among 12,349 eligible patients, 8720 (70.6%) received Empiric gram-negative antibiotics. Of those, 3240 (37.15%) received empiric narrow-spectrum gram-negative antibiotics, and 5480 (62.8%) received Empiric broad-spectrum gram-negative antibiotics. Patients receiving broad-spectrum gram-negative antibiotics were older (57.4 vs 53.8 yrs); had higher mean heart rates (97.3 vs 89.5 bpm), respiratory rates (24 vs 21.9), a fraction of inspired oxygen ( 50% vs 40%), blood sugar levels (163.4 vs 153.9 mg/dl), total leucocyte counts (12,685 vs 10,647 cells/cu mm) and serum creatinine (2.06 vs 1.03 umol/l) compared to narrow spectrum antibiotics. Similarly, patients receiving broad-spectrum gram-negative antibiotics had lower systolic blood pressure (122.6 vs 126.5 mm Hg), partial pressure of oxygen (96.7 vs 105.3), and pH ( 7.33 vs 7.36) compared to narrow-spectrum antibiotics. On multivariable regression; patients with readmission, cardiac support, and mechanical ventilation were more likely to receive broad-spectrum antibiotics. Conclusion The rate of empiric broad-spectrum gram-negative antibiotics usage in intensive care units is significantly high and associated with features of increased severity of illness.

Liver cirrhosis complicated with pulmonary Nocardia infection: A case report and literature review.

Nocardia is a conditionally pathogenic bacterium found in the natural environment and is an aerobic bacterium, which causes severe pneumonia relatively rarely. The diagnosis of primary Nocardia infection is always made late due to the nonspecific clinical presentation of patients with Nocardia infection and the time required for Nocardia culture. Due to its rarity and nonspecific clinical presentation, patient survival is often compromised due to misdiagnosis. A 53-year-old woman with autoimmune cirrhosis was treated with glucocorticoids. Three and a half months later the patient developed fever, nausea, cough and sputum, treated with empirical antibiotics, and the patient occurred type I respiratory failure. Nocardia was identified by sputum culture micromorphology and Meriere matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF). The patient was treated with trimethoprim-sulfamethoxazole (TMZ), and the patient's oxygen saturation recovered significantly. The patient's overall recovery was slow due to decreased albumin (ALB) and increased procalcitonin (PCT) caused by the patient's cirrhosis. Due to economic reasons, the family gave up, asked to be discharged. In our report, patients with underlying disease are immunocompromised and at increased risk of infection with conditionally pathogenic bacteria. Nocardia has no specific presentation and is often overlooked clinically. Treatment of these patients should not be limited to common bacteria or viruses, but should consider rare opportunistic pathogens, and we need to be vigilant for Nocardia infections and timely use of sulfonamide antibiotics to reduce mortality.

Antimicrobial Susceptibility Trends in E. coli Causing Pediatric Urinary Tract Infections in the United States

Urinary tract infections (UTIs) are among the most common pediatric infections. This study evaluated the antimicrobial susceptibility patterns of 3511 uropathogenic E. coli (UPEC) isolated from pediatric patients in the United States from 2014 to 2023. The database from the SENTRY antimicrobial surveillance program from 89 medical centers was utilized as a data source. The antimicrobial susceptibility was tested using the microbroth dilution technique against 24 antimicrobial agents. MICs were determined using the CLSI/EUCAST/FDA breakpoint criteria. All the antimicrobials reported susceptibility rates above 80% except for tetracycline (76.2%), trimethoprim–sulfamethoxazole (69.7%), and ampicillin–sulbactam (55.7%). During the study period, the susceptibility rates remained stable for most antimicrobial agents. However, significant differences were observed among age, gender, and U.S. census regions, with the Middle Atlantic showing the lowest and the Mountain region the highest susceptibility rates, for most antimicrobials. The incidence of ESBL UPEC increased from 7.1% to 10.8% between 2014 and 2023, while the prevalence of the MDR phenotype remained relatively stable. The prevalence of both ESBL and MDR phenotypes was highest among infants and young children (0–24 months), with the highest resistance rates from the Pacific region. Knowledge of the landscape of antibiotic resistance in pediatric UPEC will help healthcare providers to better tailor empiric treatment regimens for most UTI infections.

Evaluation of clinical outcomes and risk factors associated with mortality in patients with Stenotrophomonas maltophilia bloodstream infection: a multicenter study

BackgroundStenotrophomonas maltophilia, a pathogen that colonizes medical equipment and causes nosocomial infections due to its ability to form biofilms, has high mortality rates. This study investigated the risk factors related to mortality in patients who were diagnosed with S. maltophilia bacteremia.MethodsIt is a multi-center, retrospective ad observational cohort study. The demographic characteristics, clinical findings, microbiological data, and risk factors for patients were obtained from the medical records of patients at ten different hospitals between January 1, 2018, and June 30, 2023.ResultsThe study included a total of 321 patients. The observed thirty-day mortality rate was 46.1%. A central venous catheter (CVC) was present in 276 patients (86%), and in 66 of these patients (23.9%) the CVC was removed. While only 18 patients (5.6%) received appropriate empirical antibiotics, 242 (75.4%) patients received appropriate antibiotics according to antimicrobial susceptibility test (AST) results and treatment revisions. Multivariate analysis revealed that advanced age (hazard ratio [HR] = 1.02; 95% confidence interval [CI]: 1.00– 1.03), appropriate antibiotic treatment (HR = 0.35; 95% CI: 0.23–0.52), and removal of central venous catheters (HR = 0.31; 95% CI: 0.16–0.60) were significantly related to reduced mortality.ConclusionsS. maltophilia is a significant pathogen, and to reduce its high mortality rate, removal of the CVC and switching to appropriate antibiotics should be performed as soon as possible.

Ciprofloxacin-induced mucoviscosity in ESBL-positive Escherichia coli carrying the Klebsiella pneumoniae K23 capsular structure hinders phagocytosis.

Escherichia coli is a Gram-negative ubiquitous bacteria occurring in a diversity of environments including water, soil, and the gastrointestinal tract of humans and warm-blooded animals, being classified into commensal and pathogenic strains. While empirical antibiotic therapy with fluoroquinolones, such a ciprofloxacin and norfloxacin, has been a common practice, resistance to broad-spectrum cephalosporins, mediated by extended-spectrum β-lactamases (ESBLs), has been alerted as a critical priority by the World Health Organization. Additionally, the convergence of virulence and resistance has been observed in some E. coli strains, which enable these bacteria to infect humans and animals, and can jeopardize their health. Mucoviscosity phenotype has been frequently described in highly-virulent Klebsiella pneumoniae strains, whereas this phenotypic behavior remains rarely reported in E. coli. Herein, we report microbiological, genomic, and anti-phagocytic activity of ciprofloxacin-induced mucoviscosity in a CTX-M-15 (ESBL)-positive E. coli. Noteworthy, genomic analysis revealed virulence genes responsible for the synthesis of the K23 capsule type, previously described in hypermucoviscous K. pneumoniae lineages, whereas phagocytosis assays confirmed the ability of K23 E. coli strain to evade the immune system under mucoviscosity induction by ciprofloxacin treatment.

Development of Nanomaterials-Based Agents for Selective Antibacterial Activity.

Bacterial infections continue to threaten public health due to limitations in rapid and accurate diagnostic techniques. While broad-spectrum antibiotics offer empirical treatment, their overuse has fuelled the emergence of antimicrobial resistance (AMR) pathogens, posing a critical global public health challenge. In this critical scenario, nanomaterial-based antibacterial agents emerge as a promising solution to combat bacteria and inhibit their proliferation. However, selective elimination of pathogenic bacteria is paramount. This review highlights recent advancements in developing nanomaterials for selective antibacterial activity. We categorize these agents based on their mode of action, exploring how they selectively interact with bacteria and their potential antibacterial mechanisms. This review offers crucial insights for researchers exploring the potential of nanotechnology to address the growing threat of AMR.

Emergency treatment of obstructive pyelonephritis: A single center series

Objective: This study aims to compare two different drainage methods, percutaneous nephrostomy (PCN) and retrograde ureteral double-J (DJ) stent insertion, in patients with obstructive pyelonephritis (OP).Methods: The study included 77 patients who presented to the emergency department due to stones. Type of decompression treatment (PCN or DJ stent), fever, white blood cell count (WBC), C-reactive protein (CRP) levels, urine culture, blood culture, presence of additional diseases, and antibiotic treatment were evaluated for these patients. Emergency decompressive treatment was not randomly assigned. The clinician chose the appropriate treatment method based on the patient’s condition after obtaining an informed consent. Patients under the age of 18 were categorized into three subgroups: infants, children under 10 years, and adolescents. Results: Of the 77 patients, 31 were in the DJ stent group and 46 were in the PCN group. Patients in the PCN group exhibited significantly higher fever levels before the procedure (37.6 ± 1.0°C). Additionally, the positivity rate of urine and blood cultures was higher in the PCN group. The average time to stone treatment after infection and medical treatment, as well as fever control, was shorter in the PCN group (9 ± 2.3 days). Empiric treatment with Ceftriaxone (1 g IV) was confirmed by sensitivity results of urine or blood culture in 45% of cases. None of the patients developed advanced urosepsis after the procedure, but the resolution of infection parameters was faster in the PCN group (7 ± 3.3 days). Conclusions: Both PCN and DJ stent insertion are effective and safe methods for managing obstructive pyelonephritis. It was observed that the PCN method under local anesthesia was useful in quickly controlling fever and allowing early surgical treatment. Finally, third-generation cephalosporin antibiotics are beneficial for empiric initial treatment.

Monitoring of Antibiotic Resistance Patterns Within Al-Karak Governmental Hospital, Jordan, in 2022

Background/Objectives: Antimicrobial resistance is considered one of the foremost global public health challenges, and its prevalence is increasing. In Jordan, particularly in Al-Karak Governorate, there is a lack of sufficient data on antimicrobial resistance to make accurate assessments. The main aim of the current study was to evaluate antibiotic resistance trends in clinical specimens from 2022 and assess antibiotic resistance patterns. The emphasis on the WHO antibiotic classification as Access, Watch, and Reserved (AWaRe) was adopted in the current study. Results: Among Gram-positive bacteria, Enterococcus faecalis exhibited 100% susceptibility to nitrofurantoin and 96% to vancomycin, Streptococcus viridans exhibited 100% susceptibility to teicoplanin, while CoNS (coagulase-negative Staphylococci) showed moderate resistance to Trimethoprim + Sulfamethoxazole (63%) and clindamycin (47%). Among Gram-negative bacteria, Escherichia coli and Klebsiella pneumoniae displayed high susceptibility to fosfomycin (E. coli: 95%, K. pneumoniae: 80%) and amikacin (E. coli: 93%, K. pneumoniae: 81%). Resistance was notable for trimethoprim + sulfamethoxazole (E. coli: 47%, K. pneumoniae: 53%) and nitrofurantoin (K. pneumoniae: 30%). Pseudomonas aeruginosa exhibited the highest proportion of XDR strains (15%), followed by K. pneumoniae (11%) and E. coli (4%), while PDR strains were found in P. aeruginosa (6%), K. pneumoniae (3%), and E. coli (0.6%). XDR was observed in 4% of CoNS and 3% of S. viridans (α), with Staphylococcus aureus exhibiting both XDR and PDR at 1%. Methods: A cross-sectional retrospective study of bacterial species and their antimicrobial susceptibility was carried out at a hospital in Al Karak, Jordan, from January to December of 2022, the study included 1187 isolates from all locations in Al-Karak Governmental Hospital. Conclusions: The significant prevalence of XDR and PDR strains in key pathogens, particularly P. aeruginosa and K. pneumoniae, underscores the need for a robust Antimicrobial Stewardship Program (ASP) and infection control measures at Al-Karak Governmental Hospital. High susceptibility in several Access group antibiotics (e.g., amikacin and nitrofurantoin) supports their prioritization in empirical therapy, while the emergence of resistance in Watch and Reserved antibiotics highlights the necessity for rational use. These findings are very important for adjusting the local strategies to lower the spread of resistant strains and improve clinical outcomes.

Determination of antimicrobial resistance genes in patients with infected miscarriage. A rapid identification and optimized empirical therapy

BACKGROUND: The infectious factor during pregnancy remains the leading cause not only of maternal mortality, but also of premature pregnancy loss and subsequent reproductive function impairment. Patients with infected miscarriage represent a special cohort in terms of complexity of clinical decision-making, while the choice of antimicrobial chemotherapy is particularly difficult in conditions of accumulation of scientific knowledge about the main microbial agents. For adequate treatment, it is essential to use all modern methods of microbiota diagnosis and conduct regular monitoring of microorganism resistance in order to update empirical schemes of antibacterial therapy. AIM: The aim of this study was to evaluate the correlation relationship between antimicrobial resistance genes and identified microbial agents in patients with infected miscarriage in order to optimize empirical antimicrobial chemotherapy. MATERIALS AND METHODS: We prospectively studied 42 samples of genital tract discharge in patients with infected miscarriage. The classical culture method was used to determine microorganism sensitivity to standard antibacterial drugs by the disc diffusion test. A molecular genetic study of the species composition of clinically significant microbial agents and genes of resistance to β-lactam and glycopeptide antibiotics was performed using Femoflor Screen and BakRezista GLA test systems (“DNA-Technology” LLC., Russia), respectively. RESULTS: In the cultural study, one microbial agent was identified in 59.5% of cases, two in 40.0% of cases, and three in 7.1% of cases. The following microorganisms were most frequently identified: Enterococcus spp. in 25.0% of cases, Esherichia coli in 16.7% of cases, and Candida spp. in 11.7% of cases. During the molecular genetic study, Lactobacillus spp. were identified in 64.3% of the samples, the microorganisms associated with bacterial vaginosis in 45.3% of the samples, Candida spp. in 23.8% of the samples, and Herpesviridae family viruses in 14.3% of the samples. In 45.2% of the samples, one to 14 genes of resistance to β-lactam and glycopeptide antibiotics were identified, while Tem (19.0%), Oxa-40-like (19.0%), Stx-M1 (14.3%), Ges (14.3%), Oxa-51-like (11.9%), and Van A/B (9.5%) were most frequently determined in the samples positive for resistance genes. Comparison between phenotypic susceptibility testing and genetic prediction for antibiotics resistance demonstrated that the specificity varied from 96.4 to 100%, and the sensitivity from 40.0 to 85.7%. CONCLUSIONS: The use of molecular genetic diagnostic methods allows for the identification of clinically significant urogenital tract infections and the detection of markers of their resistance to β-lactam antibiotics and glycopeptides in the shortest possible time. The data obtained make it possible to optimize the initial antimicrobial chemotherapy.

Revisiting mutational resistance to ampicillin and cefotaxime in Haemophilus influenzae

BackgroundHaemophilus influenzae is an opportunistic bacterial pathogen that can cause severe respiratory tract and invasive infections. The emergence of β-lactamase-negative ampicillin-resistant (BLNAR) strains and unclear correlations between genotypic (i.e., gBLNAR) and phenotypic resistance are challenging empirical treatments and patient management. Thus, we sought to revisit molecular resistance mechanisms and to identify new resistance determinants of H. influenzae.MethodsWe performed a systematic meta-analysis of H. influenzae isolates (n = 291) to quantify the association of phenotypic ampicillin and cefotaxime resistance with previously defined resistance groups, i.e., specific substitution patterns of the penicillin binding protein PBP3, encoded by ftsI. Using phylogenomics and a genome-wide association study (GWAS), we investigated evolutionary trajectories and novel resistance determinants in a public global cohort (n = 555) and a new clinical cohort from three European centers (n = 298), respectively.ResultsOur meta-analysis confirmed that PBP3 group II- and group III-related isolates were significantly associated with phenotypic resistance to ampicillin (p < 0.001), while only group III-related isolates were associated with resistance to cefotaxime (p = 0.02). The vast majority of H. influenzae isolates not classified into a PBP3 resistance group were ampicillin and cefotaxime susceptible. However, particularly group II isolates had low specificities (< 16%) to rule in ampicillin resistance due to clinical breakpoints classifying many of them as phenotypically susceptible. We found indications for positive selection of multiple PBP3 substitutions, which evolved independently and often step-wise in different phylogenetic clades. Beyond ftsI, other possible candidate genes (e.g., oppA, ridA, and ompP2) were moderately associated with ampicillin resistance in the GWAS. The PBP3 substitutions M377I, A502V, N526K, V547I, and N569S were most strongly related to ampicillin resistance and occurred in combination in the most prevalent resistant haplotype H1 in our clinical cohort.ConclusionsGradient agar diffusion strips and broth microdilution assays do not consistently classify isolates from PBP3 groups as phenotypically resistant. Consequently, when the minimum inhibitory concentration is close to the clinical breakpoints, and genotypic data is available, PBP3 resistance groups should be prioritized over susceptible phenotypic results for ampicillin. The implications on treatment outcome and bacterial fitness of other extended PBP3 substitution patterns and novel candidate genes need to be determined.

Effect of empiric antibiotics against Pseudomonas aeruginosa on mortality in hospitalized patients: a systematic review and meta-analysis.

Empiric antibiotics active against Pseudomonas aeruginosa are recommended by professional societies for certain infections and are commonly prescribed for hospitalized patients. The effect of this practice on mortality is uncertain. A systematic literature search was conducted using Embase, Medline, PubMed, Web of Science, Cochrane, Scopus and Google Scholar from earliest entry through 9 October 2023. We included studies of patients hospitalized with P. aeruginosa infections that compared mortality rates depending on whether patients received active empiric antibiotics. We found 27 studies of 12 522 patients that reported adjusted OR of active empiric antibiotics on mortality. The pooled adjusted OR was 0.40 (95% CI, 0.32-0.50), favouring active empiric antibiotics. In practice, the mortality effect of empiric antibiotics against P. aeruginosa depends on the prevalence of P. aeruginosa and baseline mortality. The estimated absolute mortality benefit was 0.02% (95% CI, 0.02-0.02) for soft tissue infections, 0.12% (95% CI, 0.10-0.13) for urinary tract infections and community-acquired pneumonia, 0.3% (0.25-0.34) for sepsis without shock, 1.1% (95% CI, 0.9-1.4) for septic shock and 2.4% (95% CI, 1.9-2.8) for nosocomial pneumonia. The mortality effect for empiric antibiotics against P. aeruginosa depends crucially on the prevalence of P. aeruginosa and baseline mortality by type of infection. For soft tissue infections, urinary tract infections and community-acquired pneumonia, the mortality benefit is low. Meaningful benefit of empiric antibiotics against P. aeruginosa is limited to patients with approximately 30% mortality and 5% prevalence of P. aeruginosa, which is largely limited to patients in intensive care settings.

A Day Saved is a Life Saved: Direct Antimicrobial Susceptibility Testing from Positively Flagged Blood Culture Bottles and their Concordance with the Routine Method.

Sepsis is a major health problem worldwide and is associated with high morbidity and mortality with every hour delay in initiation of therapy. A conventional method of blood culture and Antimicrobial Susceptibility Testing (AST) takes around 48-72 hours. Empirical antibiotics need to be administered until the sensitivity report is made available. It has been estimated that 20-50% of the empirical antibiotics are inappropriate, resulting in prolonged hospital stays, adverse effects, and emergence of drug resistance. Additionally, this also puts an extra financial burden on both the patients and healthcare settings. Performing direct Antimicrobial Sensitivity Testing (dAST) is an important tool to reduce turn-around time (TAT) by at least 18-24 hours, thus reducing morbidity and mortality among critically ill patients. Direct AST (dAST) was performed from the positively flagged blood culture bottles received between December, 2021 to May, 2022 from Intensive Care Units (ICUs) on Mueller- Hinton Agar (MHA) using four drops of withdrawn blood. dAST was performed for six drugs: Ceftriaxone-30 μg (CTR), Piperacillin/Tazobactam-100/10 μg (PIT), Meropenem-10 μg (MRP), Ciprofloxacin-5 μg (CIP), Aztreonam-30 μg (AT), and Colistin (CL). The zone of inhibition was interpreted as per CLSI M100 ed32, 2022 guidelines. A parallel conventional method was also performed to examine for categorical agreement and disagreement. Identification was carried out using MALDI-TOF MS from the colonies that appeared on the dAST plate on the subsequent day. A total of 162 positively flagged blood culture bottles were included in the study. The majority of the Gram-negative organisms were from Enterobacterales (n=109), followed by Acinetobacter spp. (n=28) and Pseudomonas aeruginosa (n=25). Out of the 972 isolate-antimicrobial combinations, overall Categorical Agreement (CA) was seen in 936 (96.3%), whereas disagreement was observed in 36 with minor error (mE) in 21 (2.2%), major error (ME) in 7 (0.7%), and very major error (VME) in 8 (0.8%) when compared to the routine method. Categorical agreement (CA) of > 99% was seen in ceftriaxone (CTR) and ciprofloxacin (CIP). In comparison, the lowest CA was observed with meropenem (MRP) at 92%. Colistin dAST was performed using the E-strip method, and the result obtained was highly convincing, with an overall disagreement of only 1.2%. Rapid dAST from positively flagged blood culture bottles proved to significantly reduce the TAT from the time of sample collection to the first availability of antimicrobial susceptibility report with excellent categorical agreement of > 95% using the conventional disc diffusion method. Results obtained were within the acceptance criteria set by U. S. Food and Drug Administration (FDA) guidelines of > 90% categorical agreement for a new method. We were able to obtain excellent concordance for colistin using the E-strip method. Performing dAST not only saves a "day", but its proper implementation would save a "life".

Bartonella quintana Endocarditis in Persons Experiencing Homelessness, New York, New York, USA, 2020-2023.

Bartonella quintana infection can lead to bacillary angiomatosis, peliosis hepatis, chronic bacteremia, and culture-negative endocarditis. Transmitted by the human body louse (Pediculus humanus humanus), B. quintana infection has become an emerging disease in recent decades among persons experiencing homelessness. By using retrospective laboratory surveillance, we identified 5 cases of left-sided, culture-negative B. quintana endocarditis among persons in New York, New York, USA, during January 1, 2020-November 23, 2023. Identifications were made by using molecular assays. All patients experienced unsheltered homelessness in the year before hospitalization. Of those patients, 4 experienced heart failure, 3 renal failure, and 2 embolic strokes; 2 died. Aortic valve replacement occurred in 4 cases. A history of possible body louse infestation was found in 4 cases. Clinicians should consider housing status and history of lice exposure in patients with suspected bartonellosis and have a low threshold for diagnostic testing and empiric treatment in patients experiencing homelessness.

From empiric anti-scabietic treatments to delusional infestation: A case report

From empiric anti-scabietic treatments to delusional infestation: A case report

Caught Between Stewardship and Resistance: How to Treat Acute Complicated Diverticulitis in Areas of Low Antimicrobial Susceptibility?

Antimicrobial resistance is one of the main threats to public health, with multidrug-resistant (MDR) pathogens on the rise across continents. Although treatment guidelines generally recommend antimicrobial therapy for acute complicated diverticulitis, they do not specify treatment pathways according to local or national resistance profiles. There is sparse data regarding specific pathogens involved in Hinchey II–IV patients who undergo surgery. This study seeks to address these issues and determine how often and what types of MDR bacteria occur in patients undergoing emergency surgery. We prospectively enrolled patients admitted between 2020–2023 and who underwent emergency surgery for complicated acute diverticulitis. We analysed the inflammatory response parameters at admission, the type of surgery employed for source control, identified pathogens in the peritoneal samples, their antimicrobial susceptibility, the efficacy of antimicrobial empiric therapy, and mortality. Gram-negative bacteria were identified most often, with Escherichia coli being mostly MDR (43.9%) or extended-spectrum beta-lactamase producing (ESBL +ve) (24.4%), while most strains of Klebsiella pneumoniae were extended-spectrum beta-lactamase positive (ESBL +ve) (80%) and MDR (80%). Of the Enterococcus spp., 57.14% were vancomycin-resistant (VRE) strains. Patients with Hinchey III/IV were significantly more associated with MDR. Patients with multiple pathogens were significantly associated with ESBL+/VRE strains. Age, leucocytosis, and procalcitonin levels at admission were good indicators for mortality prediction, which occurred in four cases. In an age when antibiotic stewardship is advisable especially in emergency settings, the treatment should be tailored according to local profiles of MDR to ensure adequate outcomes for patients.

Strongyloides Hyperinfection Syndrome Following Immunosuppressant Therapy for COVID‐19: A Case Report With Literature Review

ABSTRACTStrongyloides hyperinfection and disseminated infections are usually associated with immunosuppression; these severe manifestations occur in a minority of cases. The use of immunosuppressants such as corticosteroids and Baricitinib for treating COVID‐19 pneumonia can be responsible for patients' immunosuppression and cause Strongyloides hyperinfection syndrome. The chance increases when the patient belongs to countries or regions where chronic infection with Strongyloides is more prevalent. This case report describes the clinical scenario of a 78‐year‐old man from southeastern Bangladesh who was initially diagnosed with COVID‐19 pneumonia. His condition improved after receiving corticosteroid therapy for approximately 1 month at various doses and Baricitinib therapy for more than a week due to moderate‐to‐severe COVID‐19 pneumonia. Approximately 2 months later, he presented with low‐grade fever, diarrhea, and itching throughout the body. Blood analysis revealed eosinophilia; stool examination revealed Rhabditiform larvae of Strongyloides stercoralis. The patient was diagnosed with Strongyloides hyperinfection syndrome and treated with Albendazole and Ivermectin. His clinical condition gradually improved, and he was discharged from the hospital. The stool sample was sent for a repeat microscopic examination after 14 days, which yielded a negative result. Clinicians should be more vigilant while prescribing corticosteroids and other immunosuppressants for a prolonged period. Proper screening to identify asymptomatic cases of strongyloidiasis, followed by empirical treatment of screening‐positive cases, prompt detection, and management of severe manifestations, is crucial to reduce further morbidity and mortality related to Strongyloides stercoralis.

Severe Cutaneous Toxicity in A 67-Year-Old Patient with Metastatic Urothelial Carcinoma Undergoing Therapy with Enfortumab Vedotin and Pembrolizumab.

Enfortumab vedotin (EV) combined with pembrolizumab (EV+P) is a promising first-line therapy for metastatic urothelial carcinoma. While it has shown significant efficacy, severe cutaneous adverse events such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported. We present this case as another example of severe skin off-target toxicity associated with this treatment, emphasising the importance of recognising this potential complication. A 67-year-old male with metastatic urothelial carcinoma, chronic kidney failure and liver cirrhosis presented with fever, respiratory symptoms and a pruritic rash after two doses of EV+P. The rash rapidly worsened, leading to extensive skin desquamation affecting 20-30% of his body surface area. Skin biopsies confirmed SJS with early-stage TEN (SJS/TEN overlap). The patient was treated with high-dose intravenous steroids, empirical antibiotics for neutropenia and intensive topical care. Significant re-epithelialisation occurred by day 13, and the patient was discharged on day 15 with cessation of EV+P therapy. This case demonstrates the potential for severe cutaneous toxicity in patients receiving EV+P, especially those with complex comorbidities. Early recognition and prompt, aggressive management with systemic corticosteroids are essential for improving outcomes. The case highlights the need for vigilance in monitoring for such adverse events and reporting them to improve patient safety. High clinical suspicion recognition of early signs of dermolysis is essential in managing severe cutaneous toxicity associated with enfortumab vedotin.A multidisciplinary approach the management of Stevens-Johnson syndrome/toxic epidermal necrolysis should involve a multidisciplinary team, especially in patients with complex comorbidities.Pharmacovigilance continuous monitoring and prompt reporting of adverse events to health authorities are vital for improving patient safety and therapeutic outcomes.