Effect of Cefepime/Enmetazobactam vs Piperacillin/Tazobactam on Clinical Cure and Microbiological Eradication in Patients With Complicated Urinary Tract Infection or Acute Pyelonephritis: A Randomized Clinical Trial.

Importance: Cefepime/enmetazobactam is a novel ß-lactam/ß-lactamase inhibitor combination and a potential empirical therapy for resistant gram-negative infections. Objective: To evaluate whether cefepime/enmetazobactam was noninferior to piperacillin/tazobactam for the primary outcome of treatment efficacy in patients with complicated urinary tract infections (UTIs) or acute pyelonephritis. Design, Setting, and Participants: A phase 3, randomized, double-blind, active-controlled, multicenter, noninferiority clinical trial conducted at 90 sites in Europe, North and Central America, South America, and South Africa. Recruitment occurred between September 24, 2018, and November 2, 2019. Final follow-up occurred November 26, 2019. Participants were adult patients aged 18 years or older with a clinical diagnosis of complicated UTI or acute pyelonephritis caused by gram-negative urinary pathogens. Interventions: Eligible patients were randomized to receive either cefepime, 2 g/enmetazobactam, 0.5 g (n = 520), or piperacillin, 4 g/tazobactam, 0.5 g (n = 521), by 2-hour infusion every 8 hours for 7 days (up to 14 days in patients with a positive blood culture at baseline). Main Outcomes and Measures: The primary outcome was the proportion of patients in the primary analysis set (patients who received any amount of study drug with a baseline gram-negative pathogen not resistant to either treatment and ≥105 colony-forming units [CFU]/mL in urine culture or the same pathogen present in concurrent blood and urine cultures) who achieved overall treatment success (defined as clinical cure combined with microbiological eradication [<103 CFU/mL in urine] of infection). Two-sided 95% CIs were computed using the stratified Newcombe method. The prespecified noninferiority margin was -10%. If noninferiority was established, a superiority comparison was also prespecified. Results: Among 1041 patients randomized (mean age, 54.7 years; 573 women [55.0%]), 1034 (99.3%) received study drug and 995 (95.6%) completed the trial. Among the primary analysis set, the primary outcome occurred in 79.1% (273/345) of patients receiving cefepime/enmetazobactam compared with 58.9% (196/333) receiving piperacillin/tazobactam (between-group difference, 21.2% [95% CI, 14.3% to 27.9%]). Treatment-emergent adverse events occurred in 50.0% (258/516) of patients treated with cefepime/enmetazobactam and 44.0% (228/518) with piperacillin/tazobactam; most were mild to moderate in severity (89.9% vs 88.6%, respectively). A total of 1.7% (9/516) of participants who received cefepime/enmetazobactam and 0.8% (4/518) of those who received piperacillin/tazobactam did not complete the assigned therapy due to adverse events. Conclusions and Relevance: Among patients with complicated UTI or acute pyelonephritis caused by gram-negative pathogens, cefepime/enmetazobactam, compared with piperacillin/tazobactam, met criteria for noninferiority as well as superiority with respect to the primary outcome of clinical cure and microbiological eradication. Further research is needed to determine the potential role for cefepime/enmetazobactam in the treatment of complicated UTI and pyelonephritis. Trial Registration: ClinicalTrials.gov Identifier: NCT03687255.

Bloodstream Infections in Children With Cancer: Pathogen Distribution and Antimicrobial Susceptibility Patterns Over a 10-Year Period.

Bloodstream infections (BSIs) adversely affect clinical outcome in children with cancer. Over 1 decade, this retrospective cohort study describes pathogen distribution in BSIs and antimicrobial susceptibility against empirical antibiotics frequently prescribed in children with cancer. The antibiotic efficacy was evaluated through the determination of minimal inhibitory concentrations for piperacillin-tazobactam and meropenem and by disk diffusion for remaining antibiotics. From 2004 to 2013, 398 BSIs occurred in 196 children with cancer (median age: 5.4 y), resulting in 457 bacteria. Overall, 266 (58.2%) were Gram-positive, and 191 (41.8%) were Gram-negative with a significant Gram-positive increase over time (P=0.032). Coagulase-negative staphylococci (74, 16.2%), viridans group streptococci (67, 14.7%), Escherichia coli (52, 11.4%), and Staphylococcus aureus (39, 8.5%) were the most common pathogens. Susceptibility to piperacillin-tazobactam (95.9%, P=0.419) and meropenem (98.9%, P=0.752) was stable over time, and resistance was observed among viridans group streptococci against piperacillin-tazobactam (18%) and meropenem (7%) and among Enterobacterales against piperacillin-tazobactam (3%). Vancomycin showed 98% Gram-positive activity, gentamicin 82% Gram-negative activity and ampicillin, cefotaxime, and cefuroxime were active in 50%, 72%, and 69% of pathogens, respectively, and BSI-related mortality was 0%. In conclusion, over 1 decade, we report an increase in Gram-positive BSIs, and stable, low-resistance rates against currently recommended empirical antibiotics, piperacillin-tazobactam and meropenem.

Lowered Risk of Nephrotoxicity through Intervention against the Combined Use of Vancomycin and Tazobactam/Piperacillin: A Retrospective Cohort Study.

The combined use of vancomycin (VCM) and tazobactam/piperacillin (TAZ/PIPC) is a major risk factor for nephrotoxicity. We sought to evaluate interventions against the combined use of VCM and TAZ/PIPC. This retrospective cohort study involved patients who considered the combined use of VCM and TAZ/PIPC as a treatment. Patients that had either or both antimicrobials replaced were assigned to the intervention group, whereas those who were continued on combination therapy were assigned to the comparison group. The primary endpoint was the incidence of acute kidney injury (AKI). The survival rate of patients on day 30 was evaluated as the secondary endpoint. The comparison and intervention groups were composed of 65 and 68 patients, respectively, and the incidence rates of AKI were 44.6% and 17.6%, respectively. Cox proportional hazard analysis identified the intervention as the only independent factor against AKI development, with a hazard ratio of 0.282 (95% confidence interval [CI], 0.141 to 0.565). For the incidence of AKI of grade greater than 1, the hazard ratio was 0.114 (95% CI, 0.025 to 0.497). The survival rates on day 30 in the comparison and intervention groups were 92.3% and 91.2%, respectively, with a relative risk of 0.988 (95% CI, 0.892 to 1.094). The trough VCM concentration was not associated with the incidence of AKI in patients receiving the combination therapy. This study demonstrated that intervention against the combined use of VCM and TAZ/PIPC can lower the risk of nephrotoxicity. IMPORTANCE The combined use of vancomycin (VCM) and tazobactam/piperacillin (TAZ/PIPC) is a major risk factor for nephrotoxicity. We retrospectively evaluated interventions against the combined use of VCM and TAZ/PIPC. Patients for whom either or both antimicrobials were replaced were assigned to the intervention group (65 patients), whereas those who were continued on combination therapy were assigned to the comparison group (68 patients). The primary endpoint was the incidence of acute kidney injury (AKI). The incidence rates of AKI in the intervention and comparison groups were 44.6% and 17.6%, respectively. Cox proportional hazard analysis identified intervention as the only independent factor against AKI development, with a hazard ratio of 0.282 (95% confidence interval [CI], 0.141 to 0.565). In conclusion, this study demonstrated that intervention against the combined use of VCM and TAZ/PIPC can lower the risk of nephrotoxicity.

Prolapse Surgery: What Kind of Antibiotic Prophylaxis Is Necessary?

INTRODUCTION: The aim of this study was to assess whether antibiotic prophylaxis or therapy is sufficient for laparoscopic or vaginal prolapse surgery with mesh. METHODS: This is a single-center prospective study. The study was divided into 3 groups. Protocol A: metronidazole (15 mg/kg) and piperacillin-tazobactam (2 g) 1 h before surgery and, for postoperative treatment, gentamycin (160 mg) 1 h before surgery in a single dose. Metronidazole and piperacillin-tazobactam were administered until hospital discharge. Protocol B: gentamycin and piperacillin-tazobactam in the same manner as group A. Protocol C: clindamycin (600 mg) and gentamicin (160 mg) 1 h before surgery in a single dose. RESULTS: We included 87 consecutive patients who underwent prolapse surgery involving mesh prostheses: 57 by the laparoscopic approach and 30 by the vaginal route. Of these, 30 patients were included in protocol A, 30 in protocol B, and 27 in protocol C. There were no statistically significant differences among the 3 protocols regarding any postoperative complications, except for urinary tract infections that were more in the vaginal approach than in the laparoscopic route, in protocol A (p = 0.002). CONCLUSIONS: One-shot prophylaxis can be successfully used in prolapse surgery regardless of the surgical approach.

Evaluating and Mitigating Risk of Acute Kidney Injury with the Combination of Vancomycin and Piperacillin-Tazobactam in Children.

The antibiotic combination of vancomycin (VAN) and piperacillin-tazobactam (PTZ) has been associated with an increased risk of acute kidney injury (AKI) in both adult and pediatric patients. In this review, we highlight some of the limitations of existing pediatric studies evaluating the combination of VAN/PTZ, focusing on AKI risk in specific pediatric patient populations. We also review the variability in defining AKI in children and provide guidance to clinicians for use of prospective surveillance and stewardship in mitigating the risk of AKI in pediatric patients treated with combination of VAN/PTZ. Based on review of available pediatric studies, if the combination of VAN/PTZ is selected as an empirical antibiotic combination, it should be used in those at low risk for AKI and should be used with extreme caution in patients with additional nephrotoxic risks. Systems should be in place to monitor the use of VAN/PTZ and associated renal function in those receiving this antibiotic combination.

Continuous Infusion of Piperacillin/Tazobactam and Meropenem in ICU Patients Without Renal Dysfunction: Are Patients at Risk of Underexposure?

BACKGROUND AND OBJECTIVES: Morbidity and mortality from serious infections are common in intensive care units (ICUs). The appropriateness of the antibiotic treatment is essential to combat sepsis. We aimed to evaluate pharmacokinetic/pharmacodynamic target attainment of meropenem and piperacillin/tazobactam administered at standard total daily dose as continuous infusion in critically ill patients without renal dysfunction and to identify risk factors of non-pharmacokinetic/pharmacodynamic target attainment. RESULTS: We included 118 patients (149 concentrations), 47% had microorganism isolation. Minimum inhibitory concentration (MIC) [median (interquartile range, IQR) values in isolated pathogens were: meropenem: 0.05 (0.02-0.12) mg/l; piperacillin: 3 (1-4) mg/l]. Pharmacokinetic/pharmacodynamic target attainments (100%fCss≥1xMIC, 100%fCss≥4xMIC and 100%fCss ≥ 8xMIC, respectively) were: 100%, 96.15%, 96.15% (meropenem) and 95.56%, 91.11%, 62.22% (piperacillin) for actual MIC; 98.11%, 71.70%, 47.17% (meropenem, MIC 2 mg/l), 95.83%, 44.79%, 6.25% (piperacillin, MIC 8 mg/l), 83.33%, 6.25%, 1.04% (piperacillin, MIC 16 mg/l) for EUCAST breakpoint of Enterobacteriaceae spp. and Pseudomonas spp. Multivariable linear analysis identified creatinine clearance (CrCL) as a predictive factor of free antibiotic concentrations (fCss) of both therapies (meropenem [ß = - 0.01 (95% CI - 0.02 to - 0.0; p = 0.043)] and piperacillin [ß = - 0.01 (95% CI - 0.02 to 0.01, p < 0.001)]). Neurocritical status was associated with lower piperacillin fCss [ß = - 0.36 (95% CI - 0.61 to - 0.11; p = 0.005)]. CONCLUSION: Standard total daily dose of meropenem allowed achieving pharmacokinetic/pharmacodynamic target attainments in ICU patients without renal dysfunction. Higher doses of piperacillin/tazobactam would be needed to cover microorganisms with MIC > 8 mg/l. CrCL was the most powerful factor predictive of fCss in both therapies.

Third generation cephalosporins and piperacillin/tazobactam have distinct impacts on the microbiota of critically ill patients.

Effective implementation of antibiotic stewardship, especially in critical care, is limited by a lack of direct comparative investigations on how different antibiotics impact the microbiota and antibiotic resistance rates. We investigated the impact of two commonly used antibiotics, third-generation cephalosporins (3GC) and piperacillin/tazobactam (TZP) on the endotracheal, perineal and faecal microbiota of intensive care patients in Australia. Patients exposed to either 3GC, TZP, or no ß-lactams (control group) were sampled over time and 16S rRNA amplicon sequencing was performed to examine microbiota diversity and composition. While neither treatment significantly affected diversity, numerous changes to microbiota composition were associated with each treatment. The shifts in microbiota composition associated with 3GC exposure differed from those observed with TZP, consistent with previous reports in animal models. This included a significant increase in Enterobacteriaceae and Enterococcaceae abundance in endotracheal and perineal microbiota for those administered 3GC compared to the control group. Culture-based analyses did not identify any significant changes in the prevalence of specific pathogenic or antibiotic-resistant bacteria. Exposure to clinical antibiotics has previously been linked to reduced microbiota diversity and increased antimicrobial resistance, but our results indicate that these effects may not be immediately apparent after short-term real-world exposures.

Acute Cholecystitis, Sepsis, and Disseminated Intravascular Coagulation Caused by Edwardsiella tarda in an Elderly Woman.

Edwardsiella tarda is a gram-negative bacillus associated with gastrointestinal diseases. It is rarely responsible for sepsis; however, the fatality is very high. Only two cases of E. tarda infections in patients over 90 years of age have been reported; these are not cases of sepsis associated with acute cholecystitis. We report a case of acute cholecystitis, sepsis, and disseminated intravascular coagulation (DIC) caused by E. tarda in a super-elderly woman aged over 90 years. There could be a possibility for recovery from sepsis and DIC if antimicrobial treatment responsiveness is ensured in the super-elderly.

A NSQIP-based randomized clinical trial evaluating choice of prophylactic antibiotics for pancreaticoduodenectomy.

Surgical site infection after pancreaticoduodenectomy is often caused by pathogens resistant to standard prophylactic antibiotics, suggesting that broad-spectrum antibiotics may be more effective prophylactic agents. This article describes the rationale and methodology underlying a multicenter randomized trial evaluating piperacillin-tazobactam compared with cefoxitin for surgical site infection prevention following pancreaticoduodenectomy. As the first US randomized surgical trial to utilize a clinical registry for data collection, this study serves as proof of concept for registry-based clinical trials.

Comparison of teicoplanin versus vancomycin in combination with piperacillin-tazobactam or meropenem for the risk of acute kidney injury.

We compared the rates of acute kidney injury (AKI), 7-day and 30-day mortalities, and resolution of AKI at discharge in combination therapies involving either teicoplanin (TEI) or vancomycin (VAN) with piperacillin-tazobactam (TZP) or meropenem (MER). In a single-center, retrospective cohort study, adult patients (>18 years) who had a baseline serum creatinine level within 24 h of admission and who received study antibiotics for at least 48 h were included. The primary outcome was AKI incidence after therapy per RIFLE criteria. Multivariate logistic regression and propensity score match analyses were employed for statistical comparisons. Data from 379 patients were evaluated. In multivariate analysis (MVA) of the whole cohort, TZP-VAN combination was associated with significantly higher rate of AKI as compared with TZP-TEI (aOR: 3.21, 95% CI, 1.36-7.57; p = 0.008) or with MER-VAN (aOR: 2.28, 95% CI, 1.008-5.18; p = 0.048). In MVA of the matched cohorts, TZP-VAN as compared with TZP-TEI and MER-VAN was associated with 3.96 times (95% CI, 1.48-10.63, p = 0.006) and 3.11 times (95% CI, 1.12-8.62; p = 0.028) increased risk of AKI, respectively. No differences between MER-TEI and MER-VAN combinations were detected. Seven-day and 30-day mortalities and resolution rates of AKI were similar in all comparisons. Teicoplanin can be preferred instead of VAN when combination with TZP is used particularly for patients with high AKI risk.

Nephrotoxicity from Vancomycin Combined with Piperacillin-Tazobactam: A Comprehensive Review.

BACKGROUND: Recent studies have identified the combination of vancomycin with piperacillin-tazobactam (VPT) to be associated with increased nephrotoxicity. Multiple, large cohort studies have found this widely used combination to have a higher risk of nephrotoxicity than other regimens in a variety of populations. SUMMARY: This review summarizes the epidemiology and clinical features of VPT-associated acute kidney injury (AKI). Potential mechanisms involved in the pathogenesis of this phenomenon are also discussed. Key Message: VPT-associated nephrotoxicity is a recently recognized clinical entity. Clinical strategies to minimize the risk of toxicity in this setting include antimicrobial stewardship, monitoring of kidney function, and emerging data supporting the potential role for novel biomarkers in predicting and managing AKI.

Pharmacokinetics and Pharmacodynamics of High-Dose Piperacillin-Tazobactam in Obese Patients.

BACKGROUND AND OBJECTIVE: Standard piperacillin-tazobactam (P-T) dosing may be suboptimal in obesity, but high-dose regimens have not been studied. We prospectively evaluated the pharmacokinetics and pharmacodynamics of standard- and high-dose P-T in obese adult inpatients. METHODS: Those receiving standard-dose P-T with BMI ≥ 30 kg/m2 weighing 105-139 kg or ≥ 140 kg were given up to 6.75 g or 9 g every 6 h, respectively. Patients were monitored closely for safety. Elimination phase blood samples were drawn for 28 patients on standard and high doses to calculate the pharmacokinetic values using a one-compartment model. The likelihood of pharmacodynamic target attainment (100% fT > 16/4 mg/L) on various P-T regimens was calculated using each patient's own pharmacokinetic values. RESULTS: Piperacillin and tazobactam half-lives ranged from 0.5-10.6 to 0.9-15.0 h, while volumes of distribution ranged from 13.6-54.8 to 11.5-60.1 L, respectively. Predicted dose requirements for target attainment ranged from 2.25 g every 6 h in hemodialysis patients to a 27 g/24-h continuous infusion in a patient with a short P-T half-life. An amount of 4.5 g every 6 h would have met the target for only 1/12 (8%) patients with creatinine clearance ≥ 80 mL/min and 13/28 (46%) for all enrolled patients. One patient (3%) experienced an adverse event deemed probably related to high-dose P-T. CONCLUSION: Some patients required high P-T doses for target attainment, but dosing requirements were highly variable. Doses up to 6.75 g or 9 g every 6 h may be tolerable; however, studies are needed to see if high dosing, prolonged infusions, or real-time therapeutic drug monitoring improves outcomes in obese patients. CLINICAL TRIAL REGISTRATION (CLINICALTRIALS.GOV): NCT01923363.

Chromobacterium violaceum infection on lower limb skin: A case report.

RATIONAL: Chromobacterium violaceum is a motile gram-negative bacterium. This bacterium commonly grows in tropical or subtropical areas in sewage and can cause opportunistic infections. PATIENT CONCERNS: A 50-year-old Chinese man had a skin ulcer in the middle of his left leg in front of the tibia. The diameter of the wound was 3.0 cm, the exudation was obvious, and necrotic tissue was attached to the wound. One week previously, he was working in a field where he accidentally punctured his left leg. DIAGNOSIS: C violaceum infection was diagnosed as per the results of pathogen culture from the infection site. INTERVENTIONS: He was treated with piperacillin/tazobactam (3.375 g/12 h iv) and levofloxacin (0.5 g/24 h iv) for 5 days. OUTCOMES: The patient showed good response to therapy and was discharged on day 18 after wound healing. LESSONS: C violaceum rarely infects humans. When an infection is suspected, samples should be immediately sent for microbial culture. Timely treatment on the basis of drug sensitivity test results can prevent further complications.

Successful Treatment of Severe Digitoxin Intoxication with CytoSorb® Hemoadsorption.

While several intoxications can be successfully treated with specific antidotes, intoxications with the steroid glycoside digitoxin still represent a major challenge. Besides conventional approaches, CytoSorb® hemoadsorption might be another treatment option. We report on an 81-year-old female patient treated in our intensive care unit (ICU) with severe digitoxin intoxication, acute renal failure, and urinary tract infection (UTI). As physiological digitoxin elimination kinetics are known to appear slow, and also in regard to the renal failure, the decision was made to initiate continuous renal replacement therapy combined with CytoSorb hemoadsorption. The patient was hemodynamically stabilized within the first 4 h of treatment and initially required catecholamines to be stopped within 24 h of treatment. Pre- and post-adsorber drug level measurements showed a rapid elimination of digitoxin. Antibiotic treatment with piperacillin/tazobactam was initiated, and despite CytoSorb hemoadsorption therapy and its known potential to reduce plasma concentrations of several drugs, the UTI was successfully treated. After 3 days of CytoSorb treatment, digitoxin plasma levels were stable and almost normalized, and no clinical signs of intoxication were present. Five days after presentation, the patient was transferred from the ICU in a stable condition. CytoSorb hemoadsorption may be an easily available, efficient, and less cost-intensive therapy option than treatment with the Fab fragment, which is the currently recommended therapy for digitalis intoxications. Therefore, the use of CytoSorb might represent an alternative treatment for life-threatening complications of digitoxin intoxications.

Meropenem versus piperacillin/tazobactam for febrile neutropenia in pediatric patients: efficacy of piperacillin/tazobactam as a 1-h drip infusion four times a day.

Although survival of children with hematological diseases and cancer has increased dramatically, febrile neutropenia (FN) is a frequently observed complication and is sometimes life-threatening in pediatric cancer patients. A prospective, randomized study was performed to clarify the usefulness of meropenem (MEPM) and piperacillin/tazobactam (PIPC/TAZ) for pediatric patients with FN. Ninety-nine patients with 394 episodes were randomly assigned to receive MEPM or PIPC/TAZ. MEPM was administered at 120 mg/kg/day as a 1-h drip infusion 3 times a day. On the other hand, PIPC/TAZ was administered at 360 mg/kg/day as a 1-h drip infusion 4 times a day. MEPM was effective in 69.5% of the 200 episodes, and PIPC/TAZ was effective in 77.2% of the 193 episodes. Compared with our previous study of MEPM 120 mg/kg/day as a 1-h drip infusion 3 times a day versus PIPC/TAZ 337.5 mg/kg/day as a 1-h drip infusion 3 times a day, the success rate of the MEPM group was not different. However, the success rate of the PIPC/TAZ group was higher than in the previous study (p = 0.001). In particular, the success rate in patients ≥ 15 years of age was improved in the PIPC/TAZ group of the present study compared with the previous study (p = 0.005).

Evaluation of area under the concentration-time curve-guided vancomycin dosing with or without piperacillin-tazobactam on the incidence of acute kidney injury.

OBJECTIVES: Recent studies suggest that the combination of piperacillin-tazobactam (P-T) and vancomycin increases the risk for acute kidney injury (AKI). The purpose of this study was to determine if area under the concentration-time curve (AUC)-guided vancomycin dosing reduced the incidence of AKI in a sample of patients who also received P-T. METHODS: This single-centre, retrospective, pre-post quasi-experimental study compared the incidence of AKI before and after a health-system-wide change from trough- to AUC-guided vancomycin dosing using two post-distribution levels. The primary outcome was AKI, defined as an increase in serum creatinine ≥0.5 mg/dL or 50% from baseline for two consecutive measurements, in patients who received vancomycin with or without concomitant P-T. RESULTS: In total, 636 patients were included in this study (308 trough-guided, 328 AUC-guided); of these, 118 patients in each group received concomitant P-T. The primary outcome occurred in 35 (11.4%) patients in the trough-guided group and 24 (7.3%) patients in the AUC-guided group (P=0.105). There was no difference in the incidence of AKI in the population receiving concomitant P-T between dosing strategies. The incidence of AKI was significantly higher in patients who received concomitant P-T compared with patients who did not receive concomitant P-T in both the trough-guided group [21/118 (17.8%) versus 14/190 (7.4%), respectively; P=0.003] and the AUC-guided group [16/118 (13.6%) versus 8/210 (3.8%), respectively; P=0.0011]. CONCLUSIONS: The incidence of AKI did not differ significantly between trough- and AUC-guided vancomycin dosing. Caution should be taken when combining vancomycin and P-T regardless of dosing strategy. Larger studies are needed to confirm these findings.

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.