Empirical Therapy Research Articles

Current Patient Management for Bacterial Meningitis Simultaneously Affected by Stroke.

Bacterial meningitis (BM) is a critical central nervous system infection characterized by increased risks of complications and potentially fatal outcomes. The chances of full recovery are significantly reduced in the presence of concomitant neurovascular complications such as ischemic and hemorrhagic strokes, intracerebral hemorrhage, and cerebral sinus thrombosis. Effective treatment of BM requires a targeted approach that simultaneously addresses the causative pathogen and manages the neurologically related complications. However, clinicians continue to face challenges in determining optimal pharmacotherapy for these patients.The presence of neurological complications is pivotal in determining patient outcomes, contributing to high disability and mortality rates. Early medical management is crucial and begins with essential stabilization followed by rapid diagnostic testing and the administration of empirical broad-spectrum antimicrobial therapy. The use of targeted antibiotics based on culture results is standard, with adjunct therapies such as dexamethasone and, in some cases, anticoagulants playing supportive roles. Despite the deployment of such comprehensive therapeutic strategies, the variability in treatment response and the high incidence of adverse outcomes necessitate ongoing research. This includes exploring novel therapeutic approaches and enhancing current clinical practices through retrospective studies and clinical trials to mitigate the high morbidity and mortality rates associated with BM and its complications. Strategic management is crucial for patient recovery, considering the substantial risk, a broad spectrum of complications, and fatal outcomes from this meningeal infection and stroke. The use of antimicrobial therapy with intravenous adjunct dexamethasone isthe current standard of care for patients with cerebrovascular complications and acute BM. In addition, other options that can provide benefits in complicated cases include anticoagulants and neurosurgery. Further investigation into treatment algorithms for patients with meningeal infection complicated by stroke and/or increased intracranial pressure is still needed.

Uropathogen antibiogram regional variations-Are Australian antimicrobial guidelines appropriate?

The objectives of this study are as follows: to assess the uropathogen antibiogram at two tertiary hospitals in Victoria to look at the difference in susceptibility patterns, to assess whether national guideline recommendations were applicable and to assess the feasibility of local antibiogram analysis to guide development of hospital-specific guidelines for empirical treatment of urosepsis and for pre-operative prophylaxis for urological procedures. All positive urine cultures analysed at Barwon Health and Monash Health, two tertiary hospitals in regional and metropolitan Victoria, Australia, respectively, between January 2019 and December 2020 were retrospectively identified. Data obtained included the organism cultured and their susceptibility profiles. Three thousand seven hundred and seventy-seven positive urine cultures from Barwon Health and 6821 from Monash Health were identified. The most common uropathogen was Escherichia coli, which was cultured in 53.4% and 59.1% of urine cultures at Barwon Health and Monash Health, respectively. The main differences observed were in Enterococcus spp., which were cultured in 8.8% and 4.9% of cultures at Barwon Health and Monash Health, respectively, and Candida spp. in 4.2% and 1.5% of cultures at Barwon Health and Monash Health, respectively. The largest differences were found in fluoroquinolone resistance with 12.1% of organisms resistant to ciprofloxacin at Barwon Health compared to 6.4% at Monash Health and 7.1% of organisms resistant to vancomycin compared to 20.1% at Barwon Health and Monash Health, respectively. This study demonstrates that there is considerable variability in the uropathogens and their antimicrobial susceptibility profile in two large health services in the same state. We recommend that each centre performs regular analysis of their uropathogen antibiogram to develop local guidelines for treatment and pre-operative prophylaxis for uropathogens.

Awareness of Antimicrobial Resistance and Antimicrobial Drugs Prescription Pattern in Small Animal Clinical Practice in Ogun State, Nigeria

Antimicrobial resistance (AMR) is a global health challenge in veterinary and human health, leading to monitoring of resistance and promotion of responsible antimicrobial use. This survey assessed the use of antimicrobials among government veterinarians in Ogun state, Nigeria. Clinicians were requested to fill questionnaires designed to extract information on the frequency of antibiotics use, antibiotic prescription patterns and evaluation of perception on AMR and use of antibiotics with compromised efficacy in veterinary practice in the last three years. Fifty-two (52) questionnaires were administered and duly completed upon return. Data analysis showed 100% awareness of AMR with 80.8% (42/52) agreeing to have encountered AMR in the course of managing small animal cases. The tetracycline class of antibiotics 49(94.2%) was the most prescribed, followed by aminoglycosides 40(76.9%) and fluoroquinolones 35(67.3%). Empirical therapy (34/52) 65.4% is the most common treatment option among clinicians while 18 (34.6%) out of 52 clinicians performed antibiotic susceptibility testing along with laboratory diagnosis as treatment guide. Furthermore, 75.0% of the respondents affirmed administering antibiotics formulated for human use in small animal treatment. Thirty-three (63.5%) respondents administered human antimicrobials in animals according to the recommended dosage in humans. This survey identified that AMR was common in small animals in the state studied and this may be due to the irrational use of antibiotics. Promoting antimicrobial stewardship in small animal medicine therefore is paramount to mitigating antimicrobial resistance and data obtained from this study will contribute to developing evidence-based policy on the rational use of antibiotics in small animal practice in Nigeria.

Beyond Early- and Late-onset Neonatal Sepsis Definitions: What are the Current Causes of Neonatal Sepsis Globally? A Systematic Review and Meta-analysis of the Evidence.

Sepsis remains a leading cause of neonatal mortality, particularly in low- and lower-middle-income countries (LLMIC). In the context of rising antimicrobial resistance, the etiology of neonatal sepsis is evolving, potentially making currently-recommended empirical treatment guidelines less effective. We performed a systematic review and meta-analysis to evaluate the contemporary bacterial pathogens responsible for early-onset sepsis (EOS) and late-onset neonatal sepsis (LOS) to ascertain if historical classifications-that guide empirical therapy recommendations based on assumptions around causative pathogens-may be outdated. We analyzed 48 articles incorporating 757,427 blood and cerebrospinal fluid samples collected from 311,359 neonates across 25 countries, to evaluate 4347 significant bacteria in a random-effects meta-analysis. This revealed gram-negative bacteria were now the predominant cause of both EOS (53%, 2301/4347) and LOS (71%, 2765/3894) globally. In LLMICs, the predominant cause of EOS was Klebsiella spp. (31.7%, 95% CI: 24.1-39.7%) followed by Staphylococcus aureus (17.5%, 95% CI: 8.5 to 28.4%), in marked contrast to the Streptococcus agalactiae burden seen in high-income healthcare settings. Our results reveal clear evidence that the current definitions of EOS and LOS sepsis are outdated, particularly in LLMICs. These outdated definitions may be guiding inappropriate empirical antibiotic prescribing that inadequately covers the causative pathogens responsible for neonatal sepsis globally. Harmonizing sepsis definitions across neonates, children and adults will enable a more acurate comparison of the epidemiology of sepsis in each age group and will enhance knowledge regarding the true morbidity and mortality burden of neonatal sepsis.

Antimicrobial Drug Utilization and Resistance Trends in Septicemia Patients: A Comprehensive Study at a Tertiary Care Hospital

Background: Septicemia is still among the leading causes of morbidity and mortality worldwide, especially among patients in the intensive care unit. The right use of antimicrobial agents is central to the successful management of septicemia, but increasing incidences of antimicrobial resistance are a big challenge. Objective: This study aimed to quantify the antimicrobial usage, resistant organisms, and clinical performance in septicemia patients in a tertiary healthcare facility in Bangladesh. Methods: A prospective observational study was done in the Department of Medicine, Community Based Medical College Hospital, over a period of 16 months. One hundred and ten participants with septicemia and admitted to the ICU were recruited. Demographic data, antimicrobial consumption, microbiological results, and clinical outcomes were gathered and examined. Results: Most of the patients were male (54.5%) and within the age group of 31–40 years. Cephalosporins were the most common first-line antimicrobials (13.3%), while macrolides (12.3%) and carbapenems (11.7%) were at the second and third rank, respectively. There were frequent alterations in antimicrobial therapy; in 28 percent of cases, ceftriaxone was replaced by levofloxacin. Patients with resistant infections had the advantage of a longer hospital and ICU stay of at least 1 week (p<0.01). 16% in patients with resistant infections. Conclusion: The topics discussed in this study include the issues arising from septicemia management due to antimicrobial resistance, the requirement of broad-spectrum empiric therapy, often changing antimicrobial regimens, and overall poor outcomes for such resistant infections. Overall, the present results highlight the need for strict adherence to principles of antimicrobial stewardship, local resistance pattern monitoring, and the creation of novel therapeutic interventions. Additional multi-centered trials to determine strategies against septicemia and AMR in limited resource .........

Kikuchi-Fujimoto lymphadenitis in a patient with human immunodeficiency virus infection: The importance of precision pathology.

Kikuchi-Fujimoto lymphadenitis (or histiocytic necrotising lymphadenitis) is a rare disease that is usually benign and self-limiting. A higher prevalence is reported amongst East Asian populations. No clear etiology has been identified although it has been associated with some viruses, rarely the Human Immunodeficiency Virus (HIV) and autoimmune pathologies. To date, there has only been a handful of cases reported globally in association with HIV, and this association is even rarer in the Asian context. A 20-year-old Asian ethnic Malay male, with no past medical history, presented with daily fevers and chills for 2weeks associated with constitutional symptoms and bilateral non-tender cervical, axillary and inguinal lymphadenopathy. Full blood count showed lymphocytosis with large granular lymphocytes. HIV viral load returned positive at >10million copies/mL. His absolute CD4 T helper cell count was 375cells/uL (7%). The rest of the infective and autoimmune workup were negative. Excision biopsy of an enlarged left cervical lymph node revealed Kikuchi lymphadenitis in the proliferative phase, with no evidence of lymphoproliferative disease. He was started on anti-retroviral therapy with resolution of the lymphadenopathy in 3months. We present a case of Kikuchi lymphadenitis associated with HIV. This highlights that Kikuchi lymphadenitis may mimic sinister pathologies (such as tuberculosis and lymphoma) and that it needs to be considered in the differential diagnosis before empirical treatment for tuberculosis or invasive investigations for lymphoma are done.

Reassessment of the role of combination antifungal therapy in the current era.

Given the high mortality and morbidity associated with invasive fungal diseases (IFDs), the use of combination antifungal therapies is often considered despite the dearth of data. This review aims to summarize the current state of literature of combination antifungal therapies, discussing the potential roles of newer antifungal combinations and key considerations for their clinical use. In infections other than cryptococcal meningitis or in the setting of empirical treatment for suspected azole-resistant Aspergillus infections, the utility of the combination antifungal approaches remains controversial given the paucity of well designed randomized controlled trials. Data on potential combined antifungal treatments have been primarily limited to in-vitro studies, animal models, case reports and/or observational studies. With availability of novel antifungal agents (e.g. ibrexafungerp, fosmanogepix), combination therapy to treat mould infections should be re-visited. A phase 2 clinical trial of ibrexafungerp combined with voriconazole to treat invasive pulmonary aspergillosis is on-going. There is a need to investigate the use of combination antifungal agents. This includes delineating the indication of these combined antifungal therapies and determining how to use them most appropriately in the clinical setting.

Clinical and biochemical factors for bacteria in bile among patients with acute cholangitis.

Acute cholangitis is a clinical syndrome caused by a bacterial infection in the biliary system. The bacteria could exist in the bile before bile drainage despite empirical antibiotic treatment. Patients with acute cholangitis admitted to a tertiary hospital in Southeastern China from August 2011 to September 2021 were involved when bile cultures were performed. Patient information before bile cultures and during hospitalization was extracted from the clinical record database. The risk factors related to bacteria in bile were assessed by univariable and multivairable logistic regression analysis, respectively. A total of 533 patients (66.05%) had bacterial growth in bile. Alanine aminotransferase concentration [odds ratio (OR) = 0.998, P < 0.001], absolute monocyte count (OR = 0.335, P = 0.001), and duration of antibiotic use (OR = 0.933, P = 0.026) were negatively correlated with bacteria in bile. In contrast, C-reactive protein (OR = 1.006, P = 0.003), thrombin time (OR = 1.213, P = 0.033), prothrombin time (OR = 1.210, P = 0.011), and age (OR = 1.025, P < 0.001) were positively correlated with bacteria in bile. Based on an area under the receiver operating characteristic curve of 0.737 (95% CI, 0.697-0.776, P < 0.001), combining these seven variables could efficiently predict the presence of bacteria in bile among patients with acute cholangitis. The combination of clinical indicators before bile drainage could predict the risk of bacteria in bile for patients with acute cholangitis.

Evaluating Antibiotic Misuse and Cost Analysis Among Hospitalized Dengue Virus-Infected Adults: Insights From a Retrospective Cohort Study.

Dengue is a prevalent cause of acute febrile illness, predominantly in Asia, where it necessitates supportive care without the need for antibiotics. This study aimed to evaluate antibiotic usage and analyze hospitalization costs among adults infected with the dengue virus. This retrospective cohort study was conducted at the Hospital for Tropical Diseases, Thailand, in 2022. Two independent reviewers assessed all adult cases with confirmed dengue from 2016 to 2021. Determinants of inappropriateness were analyzed using Poisson regression. The study included 249 participants with over half presenting with severe dengue or dengue with warning signs upon admission. The cumulative incidence of antibiotic use was 9.3% (95% CI, 8.23-10.47), predominantly involving empirical treatment strategies. Ceftriaxone and doxycycline were the most frequently prescribed antibiotics. Notably, patients who received empirical antibiotics showed no definite or presumed bacterial infections. Among those who received definite strategies, inappropriate durations, including both short treatments and the overuse of broad-spectrum antibiotics, were observed. A private ward admission was identified as a significant predictor of inappropriate use, with an incidence rate ratio of 4.15 (95% CI, 1.16-14.82) compared with intensive care unit admission. Direct medical costs did not differ significantly between appropriate and inappropriate uses. The incidence of antibiotic use among dengue cases was moderate; however, inappropriate use by indication was observed. Antimicrobial stewardship strategies should be encouraged, particularly in patients with dengue with warning signs admitted to a general or private ward. Direct medical costs between appropriate and inappropriate use were comparable.

Empirical Treatments for Male Infertility: A Focus on Lifestyle Modifications and Medicines.

Male infertility is a prevalent issue impacting numerous couples worldwide. This review aims to evaluate the effectiveness of empirical therapies for male infertility, focusing on both lifestyle modifications and medical treatments. This study provides a comprehensive overview of interventions aimed at improving male fertility outcomes. A thorough review of the existing literature was conducted, encompassing studies on lifestyle changes such as dietary changes, smoking cessation, alcohol moderation, and exercise. Additionally, medical treatments including selective estrogen receptor modulators, gonadotropins, aromatase inhibitors, phosphodiesterase-5 inhibitors, antioxidants, dopamine agonists, kallikrein, indomethacin, low-dose corticosteroids, alpha-blockers, and nitric oxide donors were evaluated. The study population included males diagnosed with infertility, focusing on various underlying causes. Lifestyle modifications were found to have a positive impact on sperm quality. Evidence shows that a healthy diet, smoking cessation, moderate alcohol consumption, and regular exercise improve fertility outcomes. Medical treatments demonstrated significant improvements in sperm production and quality. Selective estrogen receptor modulators and gonadotropins enhanced sperm parameters. Aromatase inhibitors and phosphodiesterase-5 inhibitors specifically improved sperm motility and increased pregnancy rates. Antioxidants, such as vitamins E and C and coenzyme Q10, reduced oxidative stress and enhanced sperm counts, motility, and morphology. Dopamine agonists, particularly cabergoline, normalized prolactin levels and improved fertility outcomes. Kallikrein therapy improved sperm parameters and increased pregnancy rates. Indomethacin treatment was associated with increased sperm concentrations and motility. Low-dose corticosteroids and alpha-blockers showed variable results, and nitric oxide donors like L-arginine enhanced sperm counts and motility. Empirical therapies, including lifestyle modifications and medical treatments, significantly enhance sperm quality and reproductive potential. These integrated approaches are essential in improving fertility outcomes in males. However, further extensive randomized trials are necessary to definitively establish the most effective treatments.

Clinical predictors of hospital-acquired bloodstream infections: A healthcare system analysis.

This study was performed to identify patient factors associated with hospital-acquired bloodstream infections (HABSI) to guide blood culture collection and empiric antibiotic therapy. A retrospective case-control study reviewed the medical records of 350 patients admitted to our health system from September 2017 to April 2020. The patients were 18 years and older and had at least one set of new positive non-contaminant blood cultures collected after 48 hours of admission, defined as HABSI. We developed clinical variables through a literature review associated with it. Univariate relationships between each variable and bacteremia were evaluated by chi-square test. A predictive model was developed through stepwise multivariate logistic regression. The univariate analysis and stepwise regression analysis showed that temperature >100.4° F (OR: 1.9, CI 1.1 to 3.4), male sex (OR: 1.8, CI 1.0 to 3.0), and platelet count <150,000/µL (OR: 1.8, CI 1.0 to 3.2) were statistically associated with a positive blood culture. This model helps identify patients with clinical characteristics associated with the likelihood of HABSI. This model can help guide the appropriate initiation of empiric antibiotics in clinical situations and assist with antibiotic stewardship.

Rapid de-escalation of anti-MRSA therapy guided by S. aureus nares screening for patients with pneumonia: protocol of a randomized controlled trial (SNAP study).

The current Infectious Disease Society of America and American Thoracic Society (IDSA/ATS) guidelines recommend linezolid or vancomycin as an empiric treatment for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in hospitalized patients with specific risk factors,. A nasal PCR-assay for MRSA, with its high negative predictive value, can guide a rapid antibiotic de-escalation avoiding unnecessary anti-MRSA treatment. The indiscriminate use of these drugs has contributed to the emergence of resistant S. aureus strains leading to adverse effects without any survival benefit, increasing hospital stays and associated costs. Aim of the study is the use of this diagnostic tool to reduce empirical anti-MRSA treatment duration in pneumonia, shortening antimicrobial therapy days while measuring in-hospital mortality, length of stay and adverse drug event incidence. It is a prospective, randomized single-center controlled trial planned to be conducted in the Azienda Consorziale Policlinico di Bari. The research project will have a duration of 12 months following the approval of the Ethical Committee of the University of Bari. The minimum sample size is 38 patients per group, for a total of 76 subjects, calculated assuming a standard deviation of 10, a power of 90%, a type I error of 5% and a 10% drop-out rate. We will enroll eligible patients ensuring their evidence-based management according to guidelines, we will perform a nasal swab for MRSA in patients in the experimental group and discontinue the empirical anti-MRSA therapy if the nasal swab result is negative. For both arms, follow-up visits will be on day 2, 5, 7, 14, and 28 relatives to the enrollment visit (day 0). Data will be collected on the clinical course of pneumonia and laboratory tests. Our study will provide evidence on the duration (in days) of the antibiotic intake as a primary outcome of the study. Secondary outcome measures include in-hospital mortality, the length of stay and days of mechanical ventilation (in VAP), and the incidence of adverse events related to the administration of the therapy. https://classic.clinicaltrials.gov/ct2/show/NCT06238297, identifier NCT06238297.

Outcomes of IVF treatments in women with antiphospholipid antibodies or antiphospholipid syndrome

BackgroundOvulation induction for in vitro fertilization (IVF) may increase intravascular thromboses among patients with antiphospholipid autoantibodies (aPLs) or antiphospholipid syndrome (APS) due to the high estrogen levels. While natural or modified natural IVF treatment cycles (MNC) are sometimes used instead of stimulated cycles with empiric anticoagulant treatment among these infertile patients, their efficacy is unclear. Materials and methodsA retrospective cohort study including all IVF cycles of patients diagnosed with aPLs or APS in a tertiary, university-affiliated hospital between 2012 and 2022. The outcomes of stimulated cycles with anticoagulants and MNC and natural IVF cycle attempts were compared. Results121 oocyte retrievals from 38 women were analyzed: 93 stimulated and 28 MNC or natural IVF cycles. The rates of cycle cancellation (0 % vs. 17.9 %, p < 0.001) and cycles in which no oocytes were retrieved (0 % vs. 43.5 %, p < 0.001) were significantly lower following stimulated cycles vs. natural and MNC. In parallel, positive β-hCG (31.9 % vs. 10.9 %, p = 0.03), clinical pregnancy rate (23.6 % and 3.6 %, p < 0.001) and live birth rates (18.1 % vs. 3.6 %, p = 0.01) were significantly higher following stimulated cycles. No thrombotic events or bleeding occurred in any cycle. ConclusionOvarian stimulation for IVF is more effective for successful pregnancy and delivery than natural cycles and MNC and can be safely undertaken in aPLs or APS women undergoing IVF. Rates of complication from hormonal treatment are not increased when treated with LMWH during ovarian stimulation.

The microbial etiology and resistance patterns of cosmetic tourism-related infections in Ireland.

Cosmetic tourism is an increasingly common phenomenon, both in Ireland and internationally. Complications associated with procedures performed abroad may manifest after the patient has traveled back to their home country with patients often presenting to local health services. Such complications can be infectious in nature requiring either antimicrobial therapy and/or source control in the form of wound debridement or radiologically guided interventional procedures. Patients who had presented to a regional plastic surgery unit between September 2021 and December 2022 with complications related to aesthetic procedures performed outside Ireland were identified in this retrospective-prospective design. Medical records were reviewed to ascertain what procedures were performed, where the procedure had taken place, the nature of complications, and microbial culture and sensitivity results. Thirty patients were identified during the study timeframe, predominantly female (n = 28) with a mean age of 40.27years (SD 10.6). Abdominoplasty was the most common procedure (n = 17), and Turkey was the most frequently cited destination (70%). Wound dehiscence accounted for the majority of complications (n = 18). Wound cultures were obtained in 80% (n = 24) of patients and a causative organism was isolated in 85% (n = 34) of cultures. Eighteen species of bacteria were identified and antimicrobial sensitivities were obtained for 16 of these. Antimicrobial resistance to commonly prescribed empiric antibiotics was noted in several isolates. Post-operative infections related to cosmetic tourism are a growing concern in plastic surgery. The bacterial etiology is varied, and antimicrobial resistance poses significant challenges, highlighting the need for early intervention and wound cultures to guide effective management.

To prescribe or not: a two-center retrospective observational study of antibiotics usage and outcomes of COVID-19 in Turkey

This retrospective cohort study conducted in Turkey between December 2020 and June 2022 aimed to assess antibiotic use, bacterial co-infections, and the associated factors on mortality in hospitalized patients with mild-to-severe COVID-19. Among the 445 patients, 80% received antibiotics, with fluoroquinolones being the most common choice, followed by beta-lactams and combinations. Various clinical and laboratory parameters, including symptoms, comorbidities, CCI, oxygen requirements, and CRP levels were observed to be elevated in the antibiotic group. Non-survivors had more ICU admissions and longer hospital stays compared to survivors. We conducted a multivariate Cox regression analysis to evaluate factors related to mortality. However, we did not find an association between antibiotic use and mortality [HR 2.7 (95% CI 0.4–20)]. The study identified significant factors associated with an antibiotic prescription, such as CCI (OR 1.6), CRP (OR 2.3), and ICU admission (OR 8.8), (p < 0.05). The findings suggest re-evaluating the necessity of antibiotics in COVID-19 cases based on clinical assessments, focusing on the presence of bacterial infections rather than empirical treatment. Further research is necessary to more accurately identify patients with bacterial co-infections who would benefit from antibiotic treatment.

Variability in Profiles and Prevalences of Gram-Negative Bacteria in Urinary Tract Infections: A Population-Based Analysis.

Objective: An increase in antimicrobial resistance (AMR) is observed worldwide, partly due to the overuse and misuse of antibiotics, which are ineffective in certain population subgroups. This negatively impacts both the healthcare system and patients. Our study aimed to investigate the current AMR profiles for the most commonly used antibiotics in treating urinary tract infections (UTIs) caused by gram-negative bacteria (GNB) across different age and gender subpopulations. By doing so, we provide valuable information for doctors managing prophylactic and empiric therapeutic treatments. Materials and Methods: We retrospectively analysed over 650,000 urine cultures collected in the Microbiology Department of a referral university hospital in Southern England from January 2014 to December 2022. A population-based analysis for subgroups was performed to rule out differences in AMR patterns. Our report was recorded at UHS as an internal audit (UHS7670). Results: 146,867 cultures were found positive for GNB growth. Nitrofurantoin showed the best sensitivity patterns for all age subgroups (0.93% for patients aged ≤ 18; 1.22% for patients aged 19-40; 2.17% for patients aged 40-60; and 3.48% for patients aged > 60), regardless of gender (male: 6.37%, female: 2.59%). Ampicillin/amoxicillin and trimethoprim showed a poor AMR profile for all age groups (>55% and >28%, respectively) and genders (>60% and >28%, respectively). All the other tested antibiotics (cefalexin, cefotaxime, ceftazidime, ciprofloxacin, co-amoxiclav, gentamicin) showed an overall good profile for GNB resistance across all subgroups. For all antibiotics except trimethoprim, the risk of developing AMR was significantly higher in the male population. We also found that people aged over 60 had a higher risk of AMR compared to the other age groups for all antibiotics, with the exception of cefotaxime and co-amoxiclav. Conclusions: With an overall rise in resistance patterns for GNB-related UTIs, certain antibiotics-particularly ampicillin/amoxicillin and trimethoprim-now exhibit very poor sensitivity profiles. However, antibiotics such as nitrofurantoin and gentamicin remain excellent options for empirically treating UTIs. It is important to note that AMR can vary across different populations, with higher resistance often found in elderly and male patients. Clinicians must stay informed about current guidelines and research to provide the best treatment options while minimizing the risk of further AMR development.

AN UPDATE ON CURRENT STATUS OF ANTIBIOTIC RESISTANCE IN SALMONELLA TYPHI: A RETROSPECTIVE ANALYSIS OF BLOOD CULTURE REPORTS FROM A TERTIARY CARE HOSPITAL

Background: Pakistan bears most of the burden of drug-resistant typhoid, challenging its healthcare systems with substantial cost. This study’s purpose is to investigate resistance in community-acquired salmonella typhi to guide its evidence-based empiric treatment. Methods: This study used retrospective data from the microbiology laboratory, Khyber Teaching Hospital, Peshawar (September 2022-March 2023). Data of routine diagnostic samples for typhoid was retrieved from the database. Kirby–Bauer disk diffusion method was employed to determine the sensitivity of S. Typhi against a panel of 21 selected antibiotic discs (not exclusively for each isolate). Results: Among 1742 suspected patients, 239 (13.92%) were positive for S. Typhi with 212/238 (89.1%), 227/233 (97.4%), and 196/239 (82.0%) isolates resistant to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole, respectively. High resistance (88.0% to ciprofloxacin) was detected against fluoroquinolones. Third-generation cephalosporins also showed poor activity with 144/158 (91.1%) and 120/136 (88.2%) resistance towards ceftriaxone and cefixime, respectively, except for cefoperazone/sulbactam (2/123, 1.6%). Among 157 tested isolates, 3 (1.9%), 9 (5.7%), and 123 (78.3%) were labeled as non-resistant, MDR, and XDR strains, respectively. XDRs were less resistant to azithromycin (1/114), piperacillin/tazobactam (1/123), carbapenems (0/123), and tigecycline (0/123). Conclusion: XDR S. Typhi was observed as the dominant strain in Peshawar regions for which azithromycin is still the drug of choice. With emerging resistance, azithromycin safety should be ensured through antibiotic stewardship principles. An interesting finding was the enhanced activity of cefoperazone/sulbactam, suggesting future studies. Alternative options are expensive antibiotics which can be used as a last resort. Keywords: Typhoid, Antibiotic resistance, Extensive drug-resistant (XDR) S. Typhi, Pakistan.

Pediatric Clinical Outcomes of Nasal Methicillin-resistant Staphylococcus aureus Polymerase Chain Reaction Utilization.

Methicillin-resistant Staphylococcus aureus (MRSA) is a clinical challenge in selecting empiric antimicrobials for pediatric infections. We implemented nasal MRSA polymerase chain reaction (nMRSA PCR) screening as a diagnostic tool and evaluated its impact on empiric antibiotic use and clinical outcomes. A retrospective single-center study of patients hospitalized with infections who were empirically prescribed anti-MRSA antibiotics was conducted prior to and following the initiation of nMRSA PCR screening. Electronic medical records, pharmacy data and bacterial cultures results were reviewed. Predictive values of nMRSA PCR testing were calculated and the duration of anti-MRSA empiric therapy and clinical outcomes preimplementation and postimplementation were compared. During the preimplementation period, there were 382 distinct episodes (294 unique patients) that met the inclusion criteria and during post-nMRSA PCR implementation, 394 episodes (360 unique patients) were identified. The median time to discontinuation of anti-MRSA antibiotics and proportion of patients prescribed anti-MRSA antibiotics at discharge were significantly lower in postimplementation compared with preimplementation period; 48 versus 56 hours, P < 0.001 and 20.1% versus 40.3%, P < 0.001, respectively. The negative and positive predictive values of nMRSA PCR compared to clinical culture results were 95.6% and 51.2%, respectively. Predefined adverse outcomes were documented in 11 patients who had early anti-MRSA discontinuation with negative nMRSA PCR results but only 3 were restarted on anti-MRSA treatment and none grew MRSA in clinical cultures. Shortened anti-MRSA antibiotic duration, high negative predictive value and low adverse events provide promising evidence that nMRSA PCR is an effective, rapid antimicrobial stewardship tool for hospitalized children.

Carbapenem resistance in Enterobacterales: Predicting clinical outcomes in bloodstream infections

PurposeCarbapenem-resistant Enterobacterales (CRE) are a global concern due to their high mortality rates and limited therapeutics. CRE-caused bloodstream infections (BSIs) are challenging to manage, especially in healthcare settings. This study aimed to investigate the predictors of mortality in BSI patients caused by CRE. MethodsA single center prospective study to examine the characteristics of BSI caused by CRE in a large academic hospital over 15 months. The main outcomes were microbiological characteristics and clinical outcomes of patients at 28 days based on a step-wise regression analysis. ResultsA total of 76 episodes of BSI due to CRE were included. The study found that the most common type of carbapenemase was OXA-48 (69.7 %, n = 53), followed by the co-existence of OXA-48 and MBL (26.3 %, n = 20), with Klebsiella pneumoniae being the most common (90 %, n = 69). Patients with OXA-48-BSI were more likely to have a urinary source of infection, while patients with MBL-BSI were more likely to have a non-urinary source of infection. All cases (100 %) had medical devices. Around 30.3 % of patients received effective empirical treatment, while 61.8 % received adequate therapy at 48 h. The overall mortality rate was 42.1 % (n = 32), and the main predictors of mortality in this study were the presence of sepsis and inadequate initial therapy, while age >65 predicted mortality in the linear regression but not the stepwise regression model. ConclusionCRE-BSIs are a serious health threat. The study highlights the need for preventive strategies focused on high-risk patients and proper device management to reduce BSI.

Distribution of Respiratory Infection Viruses in 2019-2020 Season and Determination of Oseltamivir Resistance of Influenza Viruses

Objective: This study aimed to determine the seasonal distribution of the factor data of viral agents determined by the multiplex PCR method in routine practice in patients admitted to the hospital with upper respiratory tract infection symptoms and to detect oseltamivir resistance in viruses that are positive for Influenza A (H1N1). Methods: Nasopharyngeal swab and bronchoalveolar lavage samples of 354 patients between the ages of 0-94 who were admitted to the Sakarya University Sakarya Training and Research Hospital with symptoms of upper respiratory tract infection between 12 September 2019 and 19 February 2020 were studied with the multiplex PCR method. Oseltamivir resistance was investigated in 11 samples selected from Influenza A (H1N1) positive samples by Sanger sequence analysis method. Results: One or more respiratory viruses were identified in 233 (66%) of 354 respiratory samples evaluated. Of these, 64 (27.5%) are Influenza A/H1N1, 4 (1.7%) are Influenza A/H3N2, 24 (10.3%) are Influenza B, 64 (27.5) are Respiratory. Syncytial Virus A/B (RSV A/B), 58 (24.9%) Rhinovirus/Enterovirus, 18 (7.7%) Adenovirus, 12 (5.2%) Human Metapneumo Virus (hMPV) ), 10 (4.3%) Bocavirus, 4 (1.7%) Parainfluenza 1, 7 (3%) Parainfluenza 3, 3 (1.3%) Parainfluenza 4, 5 (2.1%) were found to be Coronavirus HKU1 and 13 (5.6%) were found to be Coronavirus NL63. More than one factor was detected simultaneously in 45 of 233 positive samples (19.3%). Oseltamivir resistance was not found in any of the 11 influenza A/H1N1 positive samples. Conclusion: No oseltamivir resistance was observed in any of the Influenza A/H1N1 positive samples evaluated in this study. Periodic analysis of influenza A/H1N1 strains for oseltamivir resistance is necessary to guide empirical treatment.