Antimicrobial Stewardship Strategies Research Articles

Effective Antimicrobial Stewardship Strategies for Cost-effective Utilization of Telavancin for the Treatment of Patients With Hospital-acquired Bacterial Pneumonia Caused by Staphylococcus aureus

PurposeClinicians and stewardship programs are challenged with positioning of novel, higher priced antibiotic agents for the treatment of clinical infections. We developed a decision-analytic model to describe costs, including drug, total treatment costs, and health care outcomes, associated with telavancin (TLV) compared with vancomycin (VAN) for patients with Staphylococcus aureus (SA) hospital-acquired bacterial pneumonia (HABP). MethodsThis decision-analytic model assessed the treatment of SA-HABP with TLV versus VAN. Data were obtained from the ATTAIN (Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia) clinical trials on the following: the probability of clinical cure; probability of nephrotoxicity; and prevalence of polymicrobial infection (30%), methicillin-resistant Staphylococcus aureus (MRSA) (68%), and SA with VAN MIC ≥1 µg/mL (85%). Data on length of stay for cure (10 days), failure (10 additional days), and nephrotoxicity (3.5 days) were based on literature. Cost per treated patient and incremental cost-effectiveness ratio (ICER) per additional cure were calculated for SA-HABP and for monomicrobial SA-HABP. One-way sensitivity analyses were performed. FindingsPatients with SA-HABP were sub-grouped by methicillin susceptibility (n = 140, 32%) or resistance (n = 293, 68%), and occurrence of polymicrobial (n = 128, 30%) vs monomicrobial (n = 305, 70%) infections. Under the base case, hospital cost for patients with HABP treated with TLV was $42,564 and with VAN, it was $42,296. Telavancin was associated with higher drug ($2082) and nephrotoxicity ($467) costs and lower intensive care unit (−$1738) and ventilator (−$114) costs. ICER was $4156 per additional cure. ICER was sensitive to probabilities of cure, length of treatment in cures, intensive care unit cost, TLV cost, and additional length of stay due to failure. For monomicrobial SA-HABP, TLV was associated with a net cost savings of $907 per patient and yielded economic dominance. ImplicationsOur decision-analytic model suggests that TLV for monomicrobial SA-HABP is associated with higher drug acquisition costs but a favorable ICER relative to VAN, provided that effective antimicrobial stewardship limits therapy to 7 days. Sensitivity analyses suggest a potential economic benefit of TLV treatment with appropriate patient selection. Antimicrobial stewardship programs may be able to reduce total costs through judicious use of novel antimicrobial agents. ClinicalTrials.gov identifiers: NCT00107952 and NCT00124020.

Antimicrobial resistance in urine and skin isolates in Timor-Leste.

High rates of antimicrobial resistance (AMR) are seen throughout Southeast Asia. However, limited AMR data exist for Timor-Leste, which is situated on the south-eastern portion of the Malay Archipelago. The purpose of this study was to identify AMR in bacteria isolated from urine and skin swabs from patients in Dili, the capital of Timor-Leste. Urine and skin swabs were collected from symptomatic patients in Timor-Leste and were processed for bacterial culture. Isolates were processed in Australia using a VITEK®2 system for bacterial identification and to determine antimicrobial susceptibility according to Clinical and Laboratory Standards Institute (CLSI) guidelines. A total of 154 urine isolates and 57 skin isolates were analysed. Of the Enterobacteriaceae, 35% were resistant to ceftriaxone with an extended-spectrum β-lactamase (ESBL)-producing phenotype. Carbapenem resistance was not observed in any of the Gram-negative isolates. Of the Staphylococcus aureus isolates, 11% were of the community-associated methicillin-resistant S. aureus (CA-MRSA) phenotype. A moderately high proportion of Gram-negative urine isolates in Timor-Leste demonstrate phenotypic ESBL production, and a relatively low proportion of S. aureus isolates were methicillin-resistant. Improved understanding of AMR rates in Timor-Leste can help guide antimicrobial prescribing and inform antimicrobial stewardship strategies.

Trends and relationship between antimicrobial resistance and antibiotic use in Xinjiang Uyghur Autonomous Region, China: Based on a 3 year surveillance data, 2014-2016.

The objective of the study was to identify the trends and relations between antimicrobial resistance (AMR) and antibiotic use in the Xinjiang Uyghur Autonomous Region in Western China from 2014 to 2016. A retrospective, descriptive analysis of AMR prevalence, and trends and relations between AMR and antibiotic use during the 3-year period was performed. Third-generation cephalosporin-resistant Escherichia coli was the most prevalent resistant pathogen in terms of both resistance density and resistance proportion. A significant correlation was found between resistance density of third-generation cephalosporin-resistant Klebsiella pneumoniae and the use of beta-lactam-beta-lactamase inhibitor combinations (cc=0.63, p=0.03), quinolones (cc=0.60, p=0.04), and carbapenems (cc=0.76, p=0.004), among which only beta-lactam-beta-lactamase inhibitor combinations showed a significant correlation with third-generation cephalosporin-resistant E. coli (cc=0.63, p=0.03). For carbapenem-resistant Pseudomonas aeruginosa, not only carbapenem use (cc=0.65, p=0.02) but also penicillin (cc=0.76, p=0.004) and quinolone (cc=0.69, p=0.01) use showed significant correlation. A strong correlation was observed between the resistant proportion of third-generation cephalosporin-resistant E. coli and only the use of beta-lactam-beta-lactamase inhibitor combinations (cc=0.61, p=0.03). The association between antibiotic use and AMR, especially the implication of the difference in resistance density and resistance proportion, is crucial for local physicians and decision-makers to better use of antibiotics and allocate healthcare resources more effectively, as well as to better implement antimicrobial stewardship and effective infection control strategies.

Antibiotic Use by Pediatric Residents: Identifying Opportunities and Strategies for Antimicrobial Stewardship

To determine the antibiotic prescribing practices of pediatric residents and assess how they acquire knowledge leading to prescribing behaviors. We performed a cross-sectional electronic survey of all pediatric residents at the Children's National Medical Center and Nicklaus Children's Hospital, assessing antibiotic prescribing patterns for common pediatric infections, use of antibiograms, and factors influencing antibiotic choice. Eighty-five surveys (45%) were returned complete and included in the analysis. Increased deviations from clinical guideline recommendations were observed for antibiotic treatments of sinusitis and community-acquired pneumonia as compared with otitis media and group A streptococcal pharyngitis. Only 57% of residents reported having used antibiograms. General pediatric inpatient attending physicians were identified as the most influential source for house staff antibiotic knowledge. Results illustrate the need for better promotion and integration of clinical guidelines with antibiograms when developing antibiotic education programs for residents in training. In addition, pediatric hospitalists should play an active role in the implementation of these programs and can provide valuable insight into the development of educational programs in conjunction with graduate medical education divisions.

Using β-lactam antibiotics in patients with a history of β-lactam allergy: current concepts.

β-lactams are the most widely used antibiotic family, but they are also the most common cause of drug-induced hypersensitivity reactions. The estimated prevalence of reported penicillin allergy ranges between 9% and 12%, although a high percentage of patients with a history of penicillin allergy have no subsequent reactions on reexposure to β-lactams. A self-reported penicillin allergy has been associated with antimicrobial resistance, increased cost, intensive care admission, and death, making it essential to establish an accurate diagnosis. In addition to a thorough clinical history, diagnostic methods include skin tests, in vitro tests, and drug-challenge tests. In this review, the diagnosis and management of patients with self-reported penicillin allergy is discussed, including the recently introduced antimicrobial stewardship strategy.

The impact of antimicrobial stewardship strategies on antibiotic appropriateness and prescribing behaviours in selected countries in the Middle East: a systematic review.

Antimicrobial resistance is a global health problem and antimicrobial stewardship is an essential component of hospital policies worldwide yet little is known regarding effective implementation strategies in the Middle East. We conducted a review of studies carried out in this region that deployed different antimicrobial stewardship strategies to assess antimicrobial appropriateness and prescribing behaviours. A search of MEDLINE, EMBASE, International Pharmaceutical Abstracts, Google and Google Scholar was conducted. Twenty articles met the inclusion criteria; 2 studies evaluated strategies including prospective audit with feedback, while 18 others evaluated strategies including benchmarking antimicrobial utilization against guidelines. Recommendations for implementation of stewardship in the Middle East highlighted the importance of developing and updating local antimicrobial prescribing policies and using collaborative interdisciplinary approaches for success.

Are there any reasons to change our behavior in necrotizing fasciitis with the advent of new antibiotics?

The treatment of necrotizing fasciitis requires a multifaceted approach, consisting of surgical source control with immediate surgical debridement along with life support, clinical monitoring, and antimicrobial therapy. Many drugs are now available for the treatment of this life-threatening infectious disease, and the purpose of this review is to provide the reader with an updated overview of the newest therapeutic options. Because most necrotizing soft tissue infections are polymicrobial, broad-spectrum coverage is advisable. Acceptable monotherapy regimens include piperacillin-tazobactam or a carbapenem. However, drugs such as ceftolozane-tazobactam, ceftazidime-avibactam in association with an antianaerobic agent (metronidazole or clindamycin) are currently available as valuable alternatives. The new cephalosporins active against methicillin-resistant Staphylococcus aureus (MRSA), ceftaroline, and ceftobiprole share similar antibacterial activity against Gram-positive cocci, and they might be considered as an alternative to nonbetalactam anti-MRSA agents for necrotizing fasciitis management. Two new long-acting lypoglycopeptides - oritavancin and dalbavancin - share the indications for acute bacterial skin and skin structure infections and had similar activity against Gram-positive cocci including MRSA and streptococci. Carbapenem-sparing agents are particularly suitable for antimicrobial stewardship strategy. The new long-acting lypoglycopeptides are very effective in treating necrotizing fasciitis and are uttermost attractive for patients requiring short hospital stays and early discharge.

Variability in Antifungal and Antiviral Use in Hospitalized Children.

We analyzed antifungal and antiviral prescribing among high-risk children across freestanding children's hospitals. Antifungal and antiviral days of therapy varied across hospitals. Benchmarking antifungal and antiviral use and developing antimicrobial stewardship strategies to optimize use of these high cost agents is needed. Infect Control Hosp Epidemiol 2017;38:743-746.

The Role of Topical Antiseptic Agents Within Antimicrobial Stewardship Strategies for Prevention and Treatment of Surgical Site and Chronic Open Wound Infection.

Scope and Significance: The topical use of antiseptics for wound care has a role in an antimicrobial stewardship strategy. However, the details of this role need clarification. Further clinical research into the use of topical antiseptics in wound care would lower the risk of furthering antibiotic resistance and contribute to more effective antibiotic use. As part of this research, experimental and surveillance data are needed on the resistance and tolerance patterns associated with topical antiseptic use in wound infections. Objective: The development of antibiotic resistance presents global challenges in terms of patient harm and increased healthcare costs. The treatment of "at risk" and infected wounds contributes to this conundrum. Synergies between antibiotics and antiseptics and their appropriate combined use need exploration. Approach: A review of available evidence on the appropriateness of antiseptics as a fundamental component of antimicrobial stewardship strategies has been undertaken. Innovation: Opening up new ways of thinking and identifying gaps of knowledge will lead to optimizing justification of antimicrobial choices and combinations. This may lead to changes in practice in terms of solutions for the prevention and treatment of wound infection. Conclusion: Antiseptics are an integral part of antimicrobial stewardship strategies for the prevention and treatment of surgical site and chronic open wound infections.

Pharmacists lead bold antimicrobial stewardship strategy at two large hospitals

Pharmacists lead bold antimicrobial stewardship strategy at two large hospitals

Challenges of Antibiotic Stewardship on the Internal Medicine Ward

BackgroundAudit and feedback programs are considered to be one of the most effective antimicrobial stewardship (ASP) strategies to improve antibiotic prescribing; however, resource requirements are a limiting factor.MethodsIn a controlled, quasi-experimental study we evaluated the impact of once weekly ASP rounds conducted with one Medicine teaching team, while two Medicine teams served as controls, at a tertiary care center from November 2014 until November 2015. We assessed process measures and changes in antibiotic utilization (reported as monthly defined daily doses per 1000 patient days from November 2013 to November 2015 using statistical process control charts).ResultsIn total, 249 patients (40% of 627 patients on the team) were on anti-infectives on the day of the rounds and had been discussed, of which 18% (48/249) were already followed by infectious diseases. A total of 79 interventions were made. Reduced duration of therapy comprised over half of the recommendations (39/76, 51%). Discontinuing antibiotics on the same day was the second most common intervention (20/76, 26%). All stewardship suggestions were accepted by the Medicine team. However, no significant changes in antibiotic utilization were observed with a similar reduction in both groups for piperacillin-tazobactam and meropenem while at the same time, an increased use of first and third-generation cephalosporins was observed.ConclusionWhile the process measures demonstrated a change in the treatment plan in 1 out of 3 patients reviewed, this did not translate into a significant change in antibiotic utilization as compared with the control groups. This may be related to the comparably small proportion of patients reviewed by ASP given that rounds occurred only once a week, and were cancelled 28 times within a one year period due to limited Medicine clinician availability. There also could have been cross-contamination between the two study arms with faculty and trainees who received the intervention while on the intervention team continuing their learned practice while on a control team. Process measures are an important means to measure the impact of ASPs, as antibiotic utilization is not a sensitive metric and may not reliably reflect improvement in antibiotic management at the individual patient level.Disclosures All authors: No reported disclosures.

Penicillin Allergy Skin Testing as an Antibiotic Stewardship Intervention in Hematopoietic Cell Transplant Recipients

BackgroundPenicillin allergy de-labeling can be an effective stewardship tool at reducing cost and the use of alternative non-β-lactam antibiotics. This study aimed to determine the effect of a pre-transplant penicillin allergy skin testing (PAST) protocol on antibiotic usage and costs in an immunocompromised hematopoietic cell transplant (HCT) population.MethodsWe conducted a retrospective study of adult HCT patients at the Cleveland Clinic from July 2010-September 2016. Routine AST for HCT patients reporting allergy to β-lactam antibiotics was implemented at our institution in July 2015. We compared days of antibiotic therapy (DOT) and antibiotic costs (AC) before and after the implementation of the AST protocol. Antibiotic usage for empiric treatment of suspected bacterial infection was captured as average DOT per 1000 patient days during the index hospitalization and AC were measured as dollars per 1000 patient days. Utilization of alternative antibiotics was compared with our standard formulary agent (piperacillin/tazobactam).ResultsAmong the 1108 HSCT during the study period (N = 871 pre-and N = 237 post-PAST) β-lactam allergy was reported by 178 patients (141 [16%] pre- and 37 [16%] post-PAST, P = 0.83). PAST was performed on 8% (11/141) and 76% (28/37) of patients pre- and post-implementation. Only 2 positive PAST were noted (one in each group). There were no adverse reactions to PAST. There was no significant difference in the disease and transplant characteristics between the two groups. Average DOT (760 vs. 588; P = 0.03) and AC ($23,559 vs. $14,179; P = 0.012) decreased for all alternative antibiotics except levofloxacin (see Figures 1 and 2). Usage and cost of our institutional empiric formulary agent increased after AST implementation.ConclusionThe use of PAST to adjudicate reported β-lactam allergy in patients undergoing HCT is an effective antimicrobial stewardship strategy to lower usage and cost of alternative antibiotics and can facilitate prescribing of effective standard formulary agents when treating immunocompromised HCT patients at high-risk for infection. The impact of penicillin allergy de-labeling on Clostridium difficile infection and antibiotic resistance merits evaluation in future studies.Disclosures All authors: No reported disclosures.

Antimicrobial stewardship practices in Virginia

The Society of Healthcare Epidemiology of America, the Centers for Disease Control and Prevention, and the President's Council of Advisors on Science and Technology recognize the need to combat antimicrobial resistance through the promotion of antimicrobial stewardship programs. Health care facilities in Virginia were surveyed using a 23-item survey focused on facility characteristics and antimicrobial stewardship strategies. Antimicrobial stewardship activities were highly variable and many are missing key personnel and resources.

Hospital pharmacists take time out for antimicrobial stewardship.

Hospitals large and small are exploring pharmacy-managed antimicrobial therapy “time-outs” as part of antimicrobial stewardship strategies. In Illinois, four Northwestern Medicine hospitals—333-bed Central DuPage Hospital in Winfield, 159-bed Delnor in Geneva, 98-bed Kishwaukee in DeKalb, and 24-bed Valley West in Sandwich—recently presented findings from a study of pharmacist-led antimicrobial therapy time-outs, as did 650-bed University of Nebraska Medical Center in Omaha. The results of the two studies were presented at the October 2016 IDWeek conference in New Orleans. An antimicrobial therapy time-out, according to the Centers for Disease Control and Prevention’s (CDC’s) core elements for hospital antimicrobial stewardship programs, is a systemic evaluation, at a set time point, of the need to continue antimicrobial treatment. Although CDC recommends that hospitals adopt a policy of routinely requiring a time-out 48 hours after the initiation of antimicrobial therapy, that timing isn’t always practical. “It takes about 72 hours to turn around our cultures,” said Radhika Polisetty, clinical and infectious diseases pharmacist at Central DuPage Hospital. Thus, for their study, the pharmacists at the four Northwestern Medicine hospitals performed time-outs 72 hours after initiating therapy so that their recommendations were backed by microbiology test results.

Variability in Antifungal and Antiviral Use in Hospitalized Children

We analyzed antifungal and antiviral prescribing among high-risk children across freestanding children’s hospitals. Antifungal and antiviral days of therapy varied across hospitals. Benchmarking antifungal and antiviral use and developing antimicrobial stewardship strategies to optimize use of these high cost agents is needed. Infect Control Hosp Epidemiol 2017;38:743–746

Antimicrobial susceptibility of long term care facility and general practice urine samples in patients 65 years and older: an observational study.

Antimicrobial resistance in long-term care facilities (LTCFs) poses a risk to elderly residents. The aim of this observational study was to investigate recent patterns of antimicrobial susceptibility in urine samples submitted to the Microbiology Laboratory at Cork University Hospital (CUH) from LTCFs in the greater Cork region. The antimicrobial susceptibilities of LTCF and General Practitioner (GP) urine samples sent to CUH, for patients aged over 65 years of age, were compared. A retrospective analysis of the antimicrobial susceptibilities of urine samples submitted to the microbiology laboratory at CUH in quarter one of 2011-2014 was conducted. LTCF and GP urine sample susceptibilities, for patients over 65 years of age, were compared using Chi square statistics. Overall, the LTCF urine samples were less susceptible than GP urine samples to the antimicrobials recommended in the national urinary tract infection guidelines; trimethoprim, nitrofurantoin, cephalexin, co-amoxiclav, ciprofloxacin and amoxicillin ( P < 0.001). Important trends in antimicrobial susceptibility over the time period were noted. A significant reduction in susceptibility to co-amoxiclav was found between Q1 2011 and Q1 2014 in both settings (GP P = 0.013, LTCF P = 0.005). This study provides important information which will contribute to the revision of antimicrobial prescribing guidelines in the future. This study highlights the need for continuous surveillance of antimicrobial susceptibility trends in LTCFs. Antimicrobial stewardship strategies are urgently required to address antimicrobial resistance and appropriate antimicrobial prescribing in the LTCF setting.

Patient and public understanding and knowledge of antimicrobial resistance and stewardship in a UK hospital: should public campaigns change focus?

The rising global tide of antimicrobial resistance is a well-described phenomenon. Employing effective and innovative antimicrobial stewardship strategies is an essential approach to combat this public health threat. Education of the public and patients is paramount to enable the success of such strategies. A panel of hospital multidisciplinary healthcare professionals was set up and a short quiz containing true/false statements around antimicrobial stewardship and resistance was designed and piloted. An educational leaflet with the correct replies and supporting information was also produced and disseminated. Participants were recruited on a single day (18 November 2015) from the hospital outpatient clinics and the hospital outpatient pharmacy waiting room. One hundred and forty-five completed quizzes were returned, providing a total of 1450 answers. Overall, 934 of 1450 (64%) statements were scored correctly whilst 481 (33%) were scored incorrectly; 35 (3%) statements were left unscored. We speculate that these results may demonstrate that respondents understood the statements, as only a small proportion of statements were left unanswered. The question dealing with the definition of antimicrobial resistance and the question dealing with the definition of antimicrobial stewardship obtained the most incorrect replies (85% and 72%, respectively). However, a specific factual recall question regarding only one microorganism (MRSA) received the most correct responses (99%). We describe a simple, innovative method of engagement with patients and the general public to help educate and disseminate important public health messages around antimicrobial resistance and stewardship. We also identified the need for public health campaigns to address the knowledge gaps found around this topic.

Clinical Impact and Provider Acceptability of Real-Time Antimicrobial Stewardship Decision Support for Rapid Diagnostics in Children With Positive Blood Culture Results.

Rapid diagnostic technologies for infectious diseases have the potential to improve clinical outcomes, but guideline-recommended antimicrobial stewardship (AS) strategies are not currently optimized for rapid intervention. We evaluated the clinical impact and provider acceptability of implementing real-time AS decision support for children with positive blood culture results according to the FilmArray blood culture identification panel (BCID [BioFire Diagnostics]) at Children's Hospital Colorado. A pre-post quasi-experimental design was used to compare the outcomes of 100 postintervention children with positive blood culture results matched with 200 preintervention control children. Causative organisms in the preintervention group were identified using conventional microbiologic techniques and communicated to providers by a microbiology technologist. Postintervention organisms were identified by the BCID and communicated by an AS provider in real time with interpretation and antimicrobial recommendations. The primary outcome was time to optimal antimicrobial therapy (time from blood culture collection to start of predetermined pathogen-specific regimen or antimicrobial discontinuation for contaminants) compared by a log-rank test and Kaplan-Meier analysis. Provider acceptability of the intervention was assessed via E-mailed surveys. The median time to optimal therapy decreased from 60.2 hours before intervention to 26.7 hours after intervention (P = .001). Among children with blood cultures that contained true pathogens, the time to effective antimicrobial therapy decreased from 6.9 to 3.4 hours (P = .03). Unnecessary antibiotic initiation for children with a culture that contained organisms considered to be contaminants decreased from 76% to 26% (P < .001). Providers reported a change in management as a result of BCID results in 73% of the cases and a mean overall satisfaction rating of 4.8 on a 5-point Likert scale. Real-time AS decision support for rapid diagnostics is associated with improved antimicrobial use and high satisfaction ratings by providers.

Antimicrobial stewardship in paediatrics.

BackgroundAntibiotics are among the drugs most commonly prescribed to children in hospitals and communities. Unfortunately, a great number of these prescriptions are unnecessary or inappropriate. Antibiotic abuse and misuse have several negative consequences, including drug-related adverse events, the emergence of multidrug resistant bacterial pathogens, the development of Clostridium difficile infection, the negative impact on microbiota, and undertreatment risks. In this paper, the principle of and strategies for paediatric antimicrobial stewardship (AS) programs, the effects of AS interventions and the common barriers to development and implementation of AS programs are discussed.DiscussionOver the last few years, there have been significant shortages in the development and availability of new antibiotics; therefore, the implementation of strategies to preserve the activity of existing antimicrobial agents has become an urgent public health priority. AS is one such approach. The need for formal AS programs in paediatrics was officially recognized only recently, considering the widespread use of antibiotics in children and the different antimicrobial resistance patterns that these subjects exhibit in comparison to adult and elderly patients. However, not all problems related to the implementation of AS programs among paediatric patients are solved. The most important remaining problems involve educating paediatricians, creating a multidisciplinary interprofessional AS team able to prepare guidelines, monitoring antibiotic prescriptions and defining corrective measures, and the availability of administrative consensuses with adequate financial support. Additionally, the problem of optimizing the duration of AS programs remains unsolved. Further studies are needed to solve the above mentioned problems.ConclusionsIn paediatric patients, as in adults, the successful implementation of AS strategies has had a significant impact on reducing targeted- and nontargeted-antimicrobial use by improving the quality of care for hospitalized patients and preventing the emergence of resistance. Considering that rationalization of antibiotic misuse and abuse is the basis for reducing emergence of bacterial resistance and several clinical problems, all efforts must be made to develop multidisciplinary paediatric AS programs in hospital and community settings.

Gram-Negative Bacilli in Infants Hospitalized in The Neonatal Intensive Care Unit.

Gram-negative bacilli (GNB) account for a significant burden of infection and colonization in neonatal intensive care units (NICUs), and antibiotic resistance among these pathogens is of increasing concern. A prospective cohort study was performed in 4 NICUs between May 2009 and April 2012. The body sites from which GNB were isolated, antimicrobial susceptibilities of the GNB isolated, and antimicrobial therapy were assessed. Attending neonatologists treated 3.0% (188 of 6184) of eligible infants for GNB infection; 23% of 214 GNB isolates were nonsusceptible to antimicrobial agents, including gentamicin (14.8%), piperacillin-tazobactam (9.9%), third-generation cephalosporin (7.0%), and/or carbapenem agents (4.5%). Gentamicin was the most commonly used antibiotic overall, and much of its use was empiric. However, third-generation cephalosporin agents and cefepime were used more commonly as targeted therapy for identified Gram-negative pathogens. One-quarter of the GNB isolates were nonsusceptible to ≥1 antibiotic. Antimicrobial stewardship strategies for reducing antimicrobial use in NICUs should be implemented.