Empirical meropenem versus piperacillin/tazobactam for adult patients with sepsis (EMPRESS) trial: Protocol.

BACKGROUND: Piperacillin/tazobactam may be associated with less favourable outcomes than carbapenems in patients with severe bacterial infections, but the certainty of evidence is low. METHODS: The Empirical Meropenem versus Piperacillin/Tazobactam for Adult Patients with Sepsis (EMPRESS) trial is an investigator-initiated, international, parallel-group, randomised, open-label, adaptive clinical trial with an integrated feasibility phase. We will randomise adult, critically ill patients with sepsis to empirical treatment with meropenem or piperacillin/tazobactam for up to 30 days. The primary outcome is 30-day all-cause mortality. The secondary outcomes are serious adverse reactions within 30 days; isolation precautions due to resistant bacteria within 30 days; days alive without life support and days alive and out of hospital within 30 and 90 days; 90- and 180-day all-cause mortality and 180-day health-related quality of life. EMPRESS will use Bayesian statistical models with weak to somewhat sceptical neutral priors. Adaptive analyses will be conducted after follow-up of the primary outcome for the first 400 participants concludes and after every 300 subsequent participants, with adaptive stopping for superiority/inferiority and practical equivalence (absolute risk difference <2.5%-points) and response-adaptive randomisation. The expected sample sizes in scenarios with no, small or large differences are 5189, 5859 and 2570 participants, with maximum 14,000 participants and ≥99% probability of conclusiveness across all scenarios. CONCLUSIONS: EMPRESS will compare the effects of empirical meropenem against piperacillin/tazobactam in adult, critically ill patients with sepsis. Due to the pragmatic, adaptive design with high probability of conclusiveness, the trial results are expected to directly inform clinical practice.

Early Antibiotic Exposure and Adverse Outcomes in Very Preterm Infants at Low Risk of Early-Onset Sepsis: The EPIPAGE-2 Cohort Study.

OBJECTIVE: To assess the association between early empirical antibiotics and neonatal adverse outcomes in very preterm infants without risk factors for early-onset sepsis (EOS). STUDY DESIGN: This is a secondary analysis of the EPIPAGE-2 study, a prospective national population-based cohort that included all liveborn infants at 22-31 completed weeks of gestation in France in 2011. Infants at high risk of EOS (ie, born after preterm labor or preterm premature rupture of membranes or from a mother who had clinical chorioamnionitis or had received antibiotics during the last 72 hours) were excluded. Early antibiotic exposure was defined as antibiotic therapy started at day 0 or day 1 of life, irrespective of the duration and type of antibiotics. We compared treated and untreated patients using inverse probability of treatment weighting based on estimated propensity scores. RESULTS: Among 648 very preterm infants at low risk of EOS, 173 (26.2%) had received early antibiotic treatment. Early antibiotic exposure was not associated with death or late-onset sepsis or necrotizing enterocolitis (OR, 1.04; 95% CI, 0.72-1.50); however, it was associated with higher odds of severe cerebral lesions (OR, 2.71; 95% CI, 1.25-5.86) and moderate-severe bronchopulmonary dysplasia (BPD) (OR, 2.30; 95% CI, 1.21-4.38). CONCLUSIONS: Early empirical antibiotic therapy administrated in very preterm infants at low risk of EOS was associated with a higher risk of severe cerebral lesions and moderate-severe BPD.

Initial empirical antibiotics of non-carbapenems for ESBL-producing E. coli and K. pneumoniae bacteremia in children: a retrospective medical record review.

BACKGROUND: The efficacy of non-carbapenems as an empirical antibiotic for extended-spectrum ß-lactamases (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bacteremia in children remains controversial. We compared clinical and microbial outcomes according to the types of empirical antibiotics for treating pediatric patients with ESBL-producing E. coli and K. pneumoniae bacteremia. METHODS: Data from pediatric patients aged ≤ 18 years who were hospitalized with monomicrobial ESBL-producing E. coli or K. pneumoniae bacteremia at Asan Medical Center Children's Hospital, Seoul, Korea between January 2014 and May 2019 were analyzed retrospectively. The impact of empirical therapy was assessed as 30-day all-cause mortality and 2-day microbiological outcomes evaluated by the sterility of blood cultures collected on day 2 after empirical antibiotic administration. Logistic regression analysis was used to control for the effects of confounding variables. RESULTS: A total of 53 patients with bacteremia caused by ESBL-producing E. coli (n = 29) and K. pneumoniae (n = 24) were included in this study; the median age was 3.6 years, and all had underlying comorbidities. As empirical antibiotics, 27 patients were treated with meropenem, and non-carbapenem agents were administered to 26 patients; 84.6% (22/26) were converted to carbapenem antibiotics as the definitive antibiotic by day 2 after empirical antibiotic administration. Overall, the 30-day all-cause mortality of ESBL-producing E. coli and K. pneumoniae bacteremia was 17.0% (9/53). After adjustment, there was no statistically significant association of use of a non-carbapenem agent as an empirical antibiotic with microbiological failure on day 2 and 30-day all-cause mortality [adjusted odds ratio (OR) 1.0; 95% confidence interval (CI) 0.22-4.88, and adjusted OR 0.1; 95% CI 0.01-1.56]. CONCLUSIONS: The empirical use of non-carbapenems might not be a risk factor for mortality and early microbiological outcomes in pediatric patients with ESBL-producing E. coli and K. pneumoniae BSI if early transition to appropriate antimicrobial therapy was possible.

Association between duration of early empiric antibiotics and necrotizing enterocolitis and late-onset sepsis in preterm infants: a multicenter cohort study.

The threshold to initiate empiric antibiotics for suspicion of early-onset sepsis (EOS) is low in preterm infants. Antibiotics' effects on short-term outcomes have recently been debated. We aimed at exploring the extent of early empiric antibiotic exposure (EEAE) in preterm infants and the association between the duration of EEAE with necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) within different EEAE groups. EEAE practice for suspicion of EOS was evaluated in all included infants (gestational age < 30 weeks) born in 9 centers in the Netherlands and Belgium between Oct. 2014 and Jan. 2019. EEAE association with NEC and LOS development was analyzed by multivariate regression. After excluding 56 EOS cases, 1259 infants were included. A total of 1122 infants (89.1%) were exposed to empirical antibiotics for the suspicion of EOS of whom 802 (63.7%) had short (≤ 72 h) and 320 (25.4%) prolonged EEAE (> 72 h). Infants with EEAE ≤ 72 h had a lower incidence of NEC compared to both infants without EEAE (adjusted odds ratio (aOR) 0.39; 95% confidence interval (CI) [0.19-0.80]; p = 0.01) and with prolonged EEAE (> 72 h) (aOR [95%CI]: 0.58 [0.35-0.96]; p = 0.03). With every additional day of EEAE, LOS incidence decreased (aOR [95%CI]: 0.90 [0.85-0.97]; p = 0.003). CONCLUSION: Almost 90% of preterm infants who have negative blood culture results in the first 72 h of life are exposed to EEAE under suspicion of EOS. One-fourth has prolonged EEAE. Duration of EEAE was differently associated with NEC and LOS incidence. The effects of antibiotics, and potentially induced microbial dysbiosis related to development of NEC and LOS, should further be explored. WHAT IS KNOWN: • Preterm infants often receive antibiotics empirically directly after birth for suspicion of early-onset sepsis. • The effects of the duration of early empirical antibiotic exposure on the risk for necrotizing enterocolitis and late-onset sepsis are debated. WHAT IS NEW: • Almost 90% of preterm infants with a gestational age below 30 weeks are exposed to antibiotics empirically after birth despite negative culture results. In a quarter of these culture-negative infants, empirical antibiotics are prolonged. • A short course of empirical antibiotics (≤72h) is associated with decreased odds for necrotizing enterocolitis compared to both prolonged (>72h) or no empirical antibiotics after birth. Furthermore, every additional day of empirical antibiotic exposure is associated with decreased risk for late-onset sepsis in the first month of life.

Proposed empiric antibiotic therapy for prosthetic joint infections: an analysis of the Prosthetic Joint Infection in Australia and New Zealand, Observational (PIANO) cohort.

Empiric antibiotic therapy in suspected prosthetic joint infection should cover likely pathogens while avoiding overly broad-spectrum antibiotics. We analysed individual patient data from a large prospective cohort study (Prosthetic Joint Infection in Australia and New Zealand, Observational (PIANO)) and found that causative organisms vary with the presentation type, with early post-operative infections more likely to be polymicrobial (41%) compared with late acute infections (10%). We thus propose empirical regimens tailored to the presentation type and presence or absence of sepsis.

Analysis of blood stream infections, antibiograms and clinical outcomes in haematological patients with febrile neutropenia: data from a tertiary care haematology institute in India.

Timely administration of appropriate empirical antibiotics in febrile neutropenia is crucial for favourable patient outcomes. There are guidelines in place recommending such antibiotics. However, regional variations and local epidemiological data must be evaluated to tailor the antibiotics for best possible and rational use. In this study, we audited the clinical and microbiological data of febrile neutropenic episodes occurring at a tertiary care haematology institution. Three hundred and ninety-three febrile neutropenic episodes occurring in 123 patients over a 1-year period were analysed for microbial profile, sensitivity and resistance patterns, and finally clinical outcomes. Gram-negative bacilli (GNB) blood stream infections (46.9%) were more prevalent as compared to gram-positive infections (41.9%). Overall mortality due to complicated neutropenic sepsis was 19.5% (24/123 patients). Increased resistance to carbapenems, beta-lactam beta-lactamase inhibitor combinations, aminoglycosides, fluoroquinolones, and cephalosporins were observed. Cefepime and tigecycline resistance were seen in 20% and 15% GNB isolates, respectively. Chest was the most frequent focus of infection, and acute myeloid leukaemia (AML) was the most common underlying disorder which correlated with the likelihood of death (p < 0.01). Multidrug-resistant GNB (esp. Klebsiella sp.) are still most worrisome isolates in neutropenic patients. Single-agent cefepime or piperacillin-tazobactam/tigecycline combination may be considered empirical agents. Chest infections and AML were independent predictors of poor clinical outcome in neutropenic patients. Regular audit of infections and antibiotic susceptibility data is needed to improve clinical outcomes in patients with febrile neutropenia.

Effect on 30-day mortality and duration of hospitalization of empirical antibiotic therapy in CRGNB-infected pneumonia.

BACKGROUND: The objective of this study was to investigate whether unreasonable empirical antibiotic treatment (UEAT) had an impact on 30-day mortality and duration of hospitalization in bacterial pneumonia caused by carbapenem-resistant gram-negative bacteria (CRGNB). METHODS: This was a retrospective cohort study involving CRGNB-infected pneumonia. All CRGNB-infected pneumonia patients received empirical and targeted antibiotic treatment (TAT), and they were divided into reasonable empirical antibiotic treatment (REAT) and UEAT according to whether the empirical antibiotic treatment (EAT) was reasonable. The data of the two groups were compared to analyze their influence on the 30-day mortality and hospitalization time in CRGNB-infected pneumonia patients. Moreover, we also considered other variables that might be relevant and conducted multivariable regression analysis of 30-day mortality and duration of hospitalization in CRGNB-infected pneumonia patients. RESULTS: The study collected 310 CRGNB-infected pneumonia patients, the most common bacterium is Acinetobacter baumannii (211/310 [68%]), the rest were Klebsiella pneumoniae (46/310 [15%]), Pseudomonas aeruginosa and others (53/310 [17%]). Among them, 76/310 (24.5%) patients received REAT. In the analysis of risk factors, dementia, consciousness were risk factors of 30-day mortality, pulmonary disease, hemodynamic support at culture taken day and recent surgery were risk factors for longer hospital stay. The analysis of 30-day mortality showed that UEAT was not associated with 30-day mortality for the 30-day mortality of REAT and UEAT were 9 of 76 (11.84%) and 36 of 234 (15.38%) (P = 0.447), respectively. Meanwhile, there was difference between REAT and UEAT (P = 0.023) in the analysis of EAT on hospitalization time in CRGNB-infected pneumonia patients. CONCLUSIONS: UEAT was not associated with 30-day mortality while was related to duration of hospitalization in CRGNB-infected pneumonia patients, in which Acinetobacter baumanniii accouned for the majority.

Using Genetic Distance from Archived Samples for the Prediction of Antibiotic Resistance in Escherichia coli.

The rising rates of antibiotic resistance increasingly compromise empirical treatment. Knowing the antibiotic susceptibility of a pathogen's close genetic relative(s) may improve empirical antibiotic selection. Using genomic and phenotypic data for Escherichia coli isolates from three separate clinically derived databases, we evaluated multiple genomic methods and statistical models for predicting antibiotic susceptibility, focusing on potentially rapidly available information, such as lineage or genetic distance from archived isolates. We applied these methods to derive and validate the prediction of antibiotic susceptibility to common antibiotics. We evaluated 968 separate episodes of suspected and confirmed infection with Escherichia coli from three geographically and temporally separated databases in Ontario, Canada, from 2010 to 2018. Across all approaches, model performance (area under the curve [AUC]) ranges for predicting antibiotic susceptibility were the greatest for ciprofloxacin (AUC, 0.76 to 0.97) and the lowest for trimethoprim-sulfamethoxazole (AUC, 0.51 to 0.80). When a model predicted that an isolate was susceptible, the resulting (posttest) probabilities of susceptibility were sufficient to warrant empirical therapy for most antibiotics (mean, 92%). An approach combining multiple models could permit the use of narrower-spectrum oral agents in 2 out of every 3 patients while maintaining high treatment adequacy (∼90%). Methods based on genetic relatedness to archived samples of E. coli could be used to predict antibiotic resistance and improve antibiotic selection.

Association of initial empirical antibiotic therapy with increased risk of necrotizing enterocolitis.

Whether the prophylactic use of antibiotics increase the risk of necrotizing enterocolitis (NEC) remains controversial. This review aims to investigate initial empirical antibiotic therapy (IEAT) and is associated with the risk of NEC. PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched through March 1, 2020. All studies on the impacts of antibiotic exposure on NEC development were included. Thirteen studies including 7901 participants were selected. Two reviewers independently examined the extracted data and assessed the quality of the included studies. Random-effects model was used to pool the effect estimates. We found that IEAT (≥ 5 days) was associated with an increased risk of NEC in adjusted (Odds risk [OR] 1.51, 95% confidence interval [CI] 1.22-1.87) and unadjusted (OR 2.35, 95% CI 1.54-3.57) analyses. Sensitivity analysis also supported these findings.Conclusion: The evidence suggests an association between IEAT (≥ 5 days) and the risk of NEC. Further studies are needed to address whether the association with IEAT is causal.What is Known:•Necrotizing enterocolitis (NEC) is acute inflammatory necrosis of the intestinal tractin the newborn infant.•Some observational studies have associated initial empirical antibiotics with an increased risk of subsequent NEC.What is New:•Initial empirical antibiotic therapy (IEAT) (≥ 5 days) appear to increase the risk of NEC.

Microbiologic Agents in Parent-reported Neonatal Fever.

We reviewed etiology and outcome of consecutive neonates admitted to a neonatal unit for investigation of parent-reported fever (116 neonates over 24 months). Tympanic temperature was measured at the emergency department (Te) and core temperature at the neonatal unit (Tn). Microbials were isolated in 27 patients (23%); Te and Tn were both <38°C in 13 (48%) of the 27 patients. Microbial isolation was associated with older median age (16.7 vs. 8.0 days, p = 0.004), empirical antibiotic commencement (p = 0.0003) and longer hospital stay (median 8 vs. 4.0 days, p = 0.004). Compared with respiratory viral infection, patients with bacteremia had high C-reactive protein (p = 0.005) and likely to have comorbidity of meningitis (p = 0.077). Te ≥38°C had the highest sensitivity, positive likelihood ratio and positive and negative predictive ratios for bacteremia. Parent-reported fever was associated with a 3% incidence of meningitis, 6% of bacteremia and 9% of urinary tract infection. The majority of neonates with parent-reported fever do not have serious bacterial infection. Nevertheless, recommendations about threshold of antibiotic initiation are difficult, and empirical systemic antibiotic coverage must be commenced in those neonates with Te ≥38°C or elevated C-reactive protein.

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

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

Empirical Administration of Doxycycline for Rocky Mountain Spotted Fever: A Case Report.

Rocky Mountain spotted fever (RMSF) is a tick-borne illness that can cause extreme sickness, even death, in otherwise healthy individuals. Sometimes, it is difficult to confirm the diagnosis as the rash often lags behind other symptoms of the illness and may not occur at all. Other symptoms of RMSF are nonspecific, such as fever, headache, and malaise. Besides the confirmatory serology test, antibody titers remain negative in the early phase of the illness. Here, we reported a case of a 21-year-old male who presented with fever, mild headache, body aches, joint pain, dry cough, and characteristic maculopapular rash after visiting a tick-prone area. Doxycycline was started because symptoms and laboratory values heightened our suspicion for the diagnosis of RMSF. His condition improved gradually, and his labs became normal. Our study supports the empirical use of doxycycline in suspected RMSF cases.

The CREPE Score: A Predictive Tool for Third-Generation Cephalosporin-Resistant Enterobacterales Pneumonia in Community Settings.

Purpose: To evaluate risk factors and develop a prediction score for community-acquired pneumonia caused by third-generation cephalosporin-resistant Enterobacterales (3GCR EB-CAP). Patients and Methods: A retrospective study was conducted by reviewing the medical records of patients hospitalized with community-acquired pneumonia caused by Enterobacterales (EB-CAP) between January 2015 and August 2021 at Srinagarind Hospital, Khon Kaen University, Thailand. Logistic regression was used to analyze clinical parameters associated with 3GCR EB-CAP. The coefficients of significant parameters were simplified to the nearest whole number for a prediction score, called the CREPE (third-generation Cephalosporin Resistant Enterobacterales community-acquired Pneumonia Evaluation). Results: A total of 245 patients with microbiologically confirmed EB-CAP (100 in the 3GCR EB group) were analyzed. Independent risk factors for 3GCR EB-CAP included in the CREPE score were (1) recent hospitalization within the past month (1 point), (2) multidrug-resistant EB colonization (1 point), and (3) recent intravenous antibiotic use (2 points for within the past month or 1.5 points for between one and twelve months). The CREPE score had an area under the receiver operating characteristic curve (ROC) of 0.88 (95% CI 0.84-0.93). Using a cut-off point of 1.75, the score had a sensitivity and specificity of 73.5% and 84.6%, respectively. Conclusion: In areas with high prevalence of EB-CAP, the CREPE score can assist clinicians in selecting appropriate empirical therapy and reducing overuse of broad-spectrum antibiotics.

The impact of early empirical antibiotics treatment on clinical outcome of very preterm infants: a nationwide multicentre study in China.

BACKGROUND: Infants with rule-out infections are responsible for the majority of empirical antibiotics treatment (EAT) in neonatal intensive care units (NICUs), particularly very preterm infants (VPIs). Antibiotic overuse has been linked to adverse outcomes. There is a paucity of data on the association between EAT and clinical outcomes (containing the nutritional outcomes) of VPIs without infection-related morbidities. METHODS: Clinical data of VPIs admitted in 28 hospitals in 20 provinces of China from September 2019 to December 2020 were collected. EAT of VPIs was calculated as the number of days with initial usage in the first week after birth, and then categorized into 3 groups (antibiotic exposure: none, 1-4 days, and > 4 days). Clinical characteristics, nutritional status , and the short-term clinical outcomes among 3 groups were compared and analyzed. RESULTS: In total, 1834 VPIs without infection-related morbidities in the first postnatal week were enrolled, including 152 cases (8.3%) without antibiotics, 374 cases (20.4%) with EAT ≤4 days and 1308 cases (71.3%) with EAT > 4 days. After adjusting for the confounding variables, longer duration of EAT was associated with decreased weight growth velocity and increased duration of reach of full enteral feeding in EAT > 4 days group (aß: -4.83, 95% CI: - 6.12 ~ - 3.53; aß: 2.77, 95% CI: 0.25 ~ 5.87, respectively) than those receiving no antibiotics. In addition, the risk of feeding intolerance (FI) in EAT > 4 days group was 4 times higher than that in non-antibiotic group (aOR: 4.14, 95%CI: 1.49 ~ 13.56) and 1.8 times higher than that in EAT ≤4 days group (aOR: 1.82, 95%CI: 1.08 ~ 3.17). EAT > 4 days was also a risk factor for greater than or equal to stage 2 necrotizing enterocolitis (NEC) than those who did not receive antibiotics (aOR: 7.68, 95%CI: 1.14 ~ 54.75) and those who received EAT ≤4 days antibiotics (aOR: 5.42, 95%CI: 1.94 ~ 14.80). CONCLUSIONS: The EAT rate among uninfected VPIs was high in Chinese NICUs. Prolonged antibiotic exposure was associated with decreased weight growth velocity, longer duration of reach of full enteral feeding, increased risk of feeding intolerance and NEC ≥ stage 2. Future stewardship interventions to reduce EAT use should be designed and implemented.

The empirical use of aminoglycosides in Ludwig's angina based on bacterial analysis of 63 cases.

PURPOSES: To determine if the empirical use of aminoglycosides is justified in Ludwig's angina based on microscopy, culture and sensitivity results. METHODS: A retrospective analysis was done on patients that presented with Ludwig's angina to the Maxillofacial and Oral surgery department at the University of Pretoria. Demographical data was extracted from patient files. Pus specimens that were submitted as part of the initial surgical intervention were analysed. RESULTS: Sixty-three patients were included in the study with the majority, 76.19% (n=48/63), comprising males. The mean patient age was 38.6 years (range 6 months to 78 years). The majority of infections (87.3%) had an odontogenic aetiology (n=55/63). Forty-four percent of the patients had immunosuppressive co-morbidities (n=28/63). Streptococci contributed 71.26% (n=62/87) of the cultured bacteria. Similar bacteria were cultured in the immunocompromised and the immunocompetent patients (p=0.672). Ninety-two percent (n=57/62) of the streptococci cultured were sensitive to penicillin. The addition of aminoglycosides to the study sample would not have made a statistically significant difference (p=0.1556). CONCLUSION: Based on the findings of this study, the empirical use of aminoglycosides is not warranted in either immunocompromised or immunocompetent patients with Ludwig's angina.

Retrospective review of bacteriological profiles and antibiogram in a tertiary neonatal unit.

Background: Neonatal sepsis remains a major cause of morbidity and mortality. Therefore, early detection and initiation of appropriate empirical antibiotic therapy are crucial. Objectives: The aim of this study was to describe the antibiogram of the neonatal intensive care unit at Grey's Hospital, a tertiary hospital in KwaZulu-Natal. Method: This was a retrospective descriptive study, reviewing positive cultures from Grey's Hospital tertiary neonatal intensive care unit (NICU) in KwaZulu-Natal, South Africa for a 3-year period (01 January 2017 to 31 December 2019). All positive cultures from all sites were included. Results: There were 1314 positive organisms cultured. Late-onset sepsis (89.3%) predominated over early-onset sepsis (10.7%). Blood was the source for 55.2% (725/1314) of positive cultures. Of the 1314 organisms cultured, 53.7% (706/1314) were Gram-positive, 45.7% (601/1314) were Gram-negative and 0.5% (7/1314) were Candida species. Klebsiella pneumoniae, 23.5% (313/1314) was the most frequent Gram-negative organism. It was noted to have high resistance to the unit's first-line antibiotic regimens; 99% were resistant to ampicillin and 92% resistant to gentamicin. Conclusion: Blood cultures yielded most positive results with a predominance of Gram-positive organisms and late-onset sepsis. A significant proportion of the cultured organisms were resistant to the first-line antimicrobials utilised in the unit, ampicillin and gentamicin. Contribution: Ongoing surveillance on positive cultures is recommended to assess the effectiveness of the unit's current empirical antimicrobial guideline.

Influence of Appropriate Empirical Antibiotic Treatment on the Prognosis of ICU Patients with HAP Caused by Carbapenem-Resistant Gram-Negative Bacteria.

Purpose: In patients with carbapenem-resistant Gram-negative bacteria (CRGNB) infection, the impact of appropriate empirical antibiotic treatment (AEAT) initialized before culture results were available remains controversial. We aimed to investigate the effect of AEAT on the prognosis of critically ill patients with hospital-acquired pneumonia (HAP) caused by CRGNB. Patients and Methods: Patients with CRGNB-infected HAP and received empirical antibiotic treatment (EAT) for at least 3 days in the intensive care unit (ICU) of a tertiary teaching hospital in China from February 2017 to September 2021 were included in the retrospective cohort study. Patients were categorized into AEAT and inappropriate empirical antibiotic treatment (IEAT) groups based on whether they received EAT covering CRGNB. The associations of AEAT with ICU and 28-day mortality were assessed using multivariable logistic regression model. Results: A total of 94 patients were enrolled, including 29 patients in AEAT group and 65 patients in IEAT group. Patients in AEAT group had a higher Sequential Organ Failure Assessment (SOFA) score (P = 0.003), levels of procalcitonin (PCT) (P = 0.001), and lactic acid (LAC) (P = 0.026); while patients in the IEAT group had a higher platelet count (PLT) (P = 0.001). There was no significant difference in the length of ICU stay between the two groups (P = 0.051). Compared with IEAT, AEAT was associated with an increased risk of 28-day mortality in the univariable logistic regression model (OR: 2.618, 95% CI: 1.063-6.448). However, after adjusted for SOFA score, PLT, PCT, and LAC level, the association between AEAT and 28-day mortality diminished (OR: 1.028, 95% CI: 0.353-2.996). AEAT showed no significant association with ICU mortality in neither univariable (OR: 1.167, 95% CI: 0.433-3.142) nor multivariable (OR: 0.357, 95% CI: 0.097-1.320) models. Conclusion: AEAT showed no significant influence on ICU or 28-day mortality in critically ill patients with HAP caused by CRGNB infection.

Risk Factors Associated with Methicillin Resistance in Hospitalized Newborn Infants with Staphylococcus aureus Infection.

Background: An increasing number of infections due to methicillin-resistant Staphylococcus aureus (S. aureus) have been reported worldwide. To explore the risk factors associated with methicillin-resistance among the neonates with confirmed S. aureus infections and thereby to help selection of appropriate empirical antibiotics. Methods: We compared a group of hospitalized neonates with culture confirmed methicillin-resistant S. aureus (MRSA) infections to a group with methicillin-sensitive S. aureus (MSSA) based on antimicrobial susceptibility reports. We used multivariable regression analysis to determine the risk factors for neonatal MRSA infections. Results: There was no difference in the ratio of local to systemic infections or mortality between the two groups. However, the total hospitalization days and the medical care expenses in the MRSA group were significantly increased when compared to that of the MSSA group. Prior use of antibiotics for more than 48 hours was an independent risk factor for neonatal acquisition of MRSA infections, while exclusive breast milk feeding was a protective factor against MRSA infections. Conclusion: Restrictions on antibiotic abuse and promotion of breast milk feeding may protect newborns from MRSA infections. Prior history of antibiotic use and exclusive breast milk feeding may be important factors to consider in the selection of appropriate empirical antibiotics for use in neonates prior to the availability of the results of antimicrobial susceptibility testing.

Spectrum of bacterial keratitis in North India: A retrospective analysis of six years at a tertiary care eye center.

Purpose: To analyze the pattern of bacterial pathogens causing infective keratitis and their resistance to the recommended antibiotics over six years. Methods: It was a retrospective study of 9,357 cases of bacterial keratitis from January 2015 to December 2020, at a tertiary care ophthalmic center. A total of 9,547 corneal specimens were obtained from the study subjects. Demographic details of the patients, pathogenic bacteria isolated, and their antimicrobial susceptibility were noted and analyzed. Results: Bacterial pathogens were identified in 23.52% of the specimens. The most common isolates were coagulase-negative Staphylococci (60.75%), followed by Pseudomonas aeruginosa (14.23%), Staphylococcus aureus (13.92%), gram negative bacilli of the family Enterobacterales (8.64%), Streptococcus spp. (1.72%), Acinetobacter spp. (0.13%), and other non-fermenting gram-negative bacilli (0.57%). In Staphylococci, 55-80% of isolates were resistant to erythromycin, and 40-70% to fluoroquinolones, while no resistance was observed against vancomycin. 40-60% of isolates of P. aeruginosa were resistant to cephalosporins, 40-55% to fluoroquinolones, and 30-60% to aminoglycosides. Also, 40-80% of isolates of Enterobacterales were resistant to cephalosporins, and 50-60% to fluoroquinolones. Most gram-negative isolates were susceptible to carbapenems and polymyxin B. Conclusion: To the best of our knowledge, our study is the largest compilation of microbiological profile of bacterial keratitis from North India. It highlights the current trend of the bacterial pathogens that cause infectious keratitis. Staphylococci and Pseudomonas were found to be the most common pathogens. Increased resistance was seen against some of the commonly prescribed empirical antibiotics. Such evidence is useful for restructuring the empirical prescription practices from time to time.

Bloodstream Infections in Hematologic Malignancy Patients With Fever and Neutropenia: Are Empirical Antibiotic Therapies in the United States Still Effective?

Background: Rising antimicrobial resistance rates may impact the efficacy of empirical antibiotic treatment for febrile neutropenia in high-risk cancer patients. Lacking contemporary data about the epidemiology, antibiotic resistance patterns, and clinical outcomes from bloodstream infections (BSIs) in US cancer patients, it is unclear if current guidelines remain relevant. Methods: In a cross-sectional study, 14 US cancer centers prospectively identified BSIs in high-risk febrile neutropenic (FN) patients, including those receiving chemotherapy for hematologic malignancies or hematopoietic stem cell transplantation. Results: Among 389 organisms causing BSI in 343 patients, there was an equal distribution of gram-negative (GN) and gram-positive (GP) bacteria, with variability across centers. Cefepime and piperacillin-tazobactam were the most commonly prescribed empirical antibiotics for FN, at 62% and 23%, respectively; a GP-directed agent was empirically included in nearly half of all FN episodes within the first 24 hours. Susceptibility to fluoroquinolones, cefepime, piperacillin-tazobactam, and carbapenems was 49%, 84%, 88%, and 96%, respectively, among GN isolates. Critical illness (CrI), defined as a new requirement for mechanical ventilation, vasopressor, or death within 30 days, occurred in 15% and did not correlate with fluoroquinolone prophylaxis, organism type, initial antibiotics, or adequacy of coverage. Only severity of illness at presentation, signified by a Pitt bacteremia score ≥2, predicted for critical illness within 30 days. Mortality was 4% by day 7 and 10% overall. Conclusions: In accordance with US guidelines, cefepime or piperacillin-tazobactam remain effective agents or empirical treatment for high-risk cancer patients with FN who are stable at presentation, maintaining high GN pathogen susceptibility and yielding excellent outcomes.