Narrow-spectrum Β-lactams Research Articles

Impact of the phenotypic expression of temocillin resistance in Escherichia coli on temocillin efficacy in a murine peritonitis model.

Temocillin is a narrow spectrum β-lactam active against MDR Enterobacterales. Mechanisms of acquired resistance to temocillin are poorly understood. We analysed resistance mechanisms in clinical isolates of Escherichia coli and evaluated their impact on temocillin efficacy in vitro and in a murine peritonitis model. Two sets of isogenic clinical E. coli strains were studied: a susceptible isolate (MLTEM16S) and its resistant derivative, MLTEM16R (mutation in nmpC porin gene); and temocillin-resistant derivatives of E. coli CFT073: CFT-ΔnmpC (nmpC deletion), CFTbaeS-TP and CFTbaeS-AP (two different mutations in the baeS efflux-pump gene).Fitness cost, time-kill curves and phenotypic expression of resistance were determined. Temocillin efficacy was assessed in a murine peritonitis model. MICs of temocillin were 16 and 64 mg/L for MLTEM16S and MLTEM16R, respectively, and 8, 128, 256 and 256 mg/L for E. coli-CFT073, CFT-ΔnmpC, CFTbaeS-TP and CFTbaeS-AP, respectively. No fitness cost of resistance was evidenced. All resistant strains showed heteroresistant profiles, except for CFTbaeS-AP, which displayed a homogeneous pattern. In vitro, temocillin was bactericidal against MLTEM16R, CFT-ΔnmpC, CFTbaeS-TP and CFTbaeS-AP at 128, 256, 512 and 512 mg/L, respectively. In vivo, temocillin was as effective as cefotaxime against MLTEM16R, CFT-ΔnmpC and CFTbaeS-TP, but inefficient against CFTbaeS-AP (100% mortality). Heteroresistant NmpC porin alteration and active efflux modification do not influence temocillin efficacy despite high MIC values, unfavourable pharmacokinetic/pharmacodynamic conditions and the absence of fitness cost, whereas homogeneously expressed BaeS efflux pump alteration yielding similar MICs leads to temocillin inefficacy. MIC as sole predictor of temocillin efficacy should be used with caution.

Incidence and variability in receipt of phenotype-desirable antimicrobial therapy for Enterobacterales bloodstream infections among hospitalized United States patients.

Using a large, geographically diverse, hospital-based database in the United States (Premier PINC AI Healthcare Database), we aimed to describe the proportion and characteristics of patients receiving phenotype-desirable antimicrobial therapy (PDAT) among those hospitalized with Enterobacterales bloodstream infections. Adult patients with an admission between January 1, 2017 and June 30, 2022 with ≥1 blood culture positive for Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, or Proteus mirabilis and receiving an empiric antibiotic therapy on blood culture collection (BCC) Days 0 or 1 were included. Receiving PDAT (defined as receipt of any antimicrobial categorized as "desirable" for the respective phenotype) on BCC Days 0-2 was defined as receiving early PDAT. Among 35,880 eligible patients, the proportion of patients receiving PDAT increased (from 6.8% to 22.8%) from BCC Day 0-4. Patients who received PDAT (8,193, 22.8%) were more likely to visit large (500 + beds, 36% vs 31%), teaching (45% vs 39%), and urban (85% vs 82%) hospitals in the Northeast (22% vs 13%) compared to patients not receiving PDAT (all P <. 01). Among patients receiving PDAT, 61.4% (n = 5,033) received it early; they had a lower mean comorbidity score (3.2 vs 3.6), were less likely to have severe or extreme severity of illness (71% vs 79%), and were less likely to have a pathogen susceptible to narrow-spectrum β-lactams (31% vs 71%) compared to patients in the delayed PDAT group (all P < .01). The proportion of patients receiving desirable therapy increased between BCC Day 0 and 4. Receipts of PDAT and early PDAT were associated with hospital, clinical, and pathogen characteristics.

Variation in antibiotic consumption in very preterm infants-a 10 year population-based study.

Wide variations in antibiotic use in very preterm infants have been reported across centres despite similar rates of infection. We describe 10 year trends in use of antibiotics and regional variations among very preterm infants in Norway. All live-born very preterm infants (<32 weeks gestation) admitted to any neonatal unit in Norway during 2009-18 were included. Main outcomes were antibiotic consumption expressed as days of antibiotic therapy (DOT) per 1000 patient days (PD), regional variations in use across four health regions, rates of sepsis and sepsis-attributable mortality and trends of antibiotic use during the study period. We included 5296 infants: 3646 (69%) were born at 28-31 weeks and 1650 (31%) were born before 28 weeks gestation with similar background characteristics across the four health regions. Overall, 80% of the very preterm infants received antibiotic therapy. The most commonly prescribed antibiotics were the combination of narrow-spectrum β-lactams and aminoglycosides, but between 2009 and 2018 we observed a marked reduction in their use from 100 to 40 DOT per 1000 PD (P < 0.001). In contrast, consumption of broad-spectrum β-lactams remained unchanged (P = 0.308). There were large variations in consumption of vancomycin, broad-spectrum β-lactams and first-generation cephalosporins, but no differences in sepsis-attributable mortality across regions. The overall antibiotic consumption was reduced during the study period. Marked regional variations remained in consumption of broad-spectrum β-lactams and vancomycin, without association to sepsis-attributable mortality. Our results highlight the need for antibiotic stewardship strategies to reduce consumption of antibiotics that may enhance antibiotic resistance development.

Assessment of flomoxef combined with amikacin in a hollow-fibre infection model for the treatment of neonatal sepsis in low- and middle-income healthcare settings.

Annual mortality from neonatal sepsis is an estimated 430 000-680 000 infants globally, most of which occur in low- and middle-income countries (LMICs). The WHO currently recommends a narrow-spectrum β-lactam (e.g. ampicillin) and gentamicin as first-line empirical therapy. However, available epidemiological data demonstrate high rates of resistance to both agents. Alternative empirical regimens are needed. Flomoxef and amikacin are two off-patent antibiotics with potential for use in this setting. To assess the pharmacodynamics of flomoxef and amikacin in combination. The pharmacodynamic interaction of flomoxef and amikacin was assessed in chequerboard assays and a 16-arm dose-ranged hollow-fibre infection model (HFIM) experiment. The combination was further assessed in HFIM experiments mimicking neonatal plasma exposures of clinically relevant doses of both drugs against five Enterobacterales isolates with a range of flomoxef/amikacin MICs. Flomoxef and amikacin in combination were synergistic in bacterial killing in both assays and prevention of emergence of amikacin resistance in the HFIM. In the HFIM assessing neonatal-like drug exposures, the combination killed 3/5 strains to sterility, (including 2/5 that monotherapy with either drug failed to kill) and failed to kill the 2/5 strains with flomoxef MICs of 32 mg/L. We conclude that the combination of flomoxef and amikacin is synergistic and is a potentially clinically effective regimen for the empirical treatment of neonatal sepsis in LMIC settings and is therefore suitable for further assessment in a clinical trial.

Indications for the use of metronidazole in the treatment of non-periodontal dental infections: a systematic review.

BackgroundDental practitioners are the largest prescribers of metronidazole. Antibiotics should only be prescribed when systemic involvement is clear and should be limited to monotherapy with β-lactams in the first instance.ObjectivesTo determine whether metronidazole used as monotherapy or in addition to a β-lactam antibiotic offers any additional benefit over β-lactam monotherapy in non-periodontal dental infections.MethodsSearches of Ovid Medline, Ovid Embase, Cochrane library and trials registries, forward and backward citations, for studies published between database inception and 2 August 2021. All randomized clinical trials (RCTs) and non-randomized trials comparing either systemic metronidazole monotherapy or metronidazole combined with a β-lactam with β-lactam monotherapy for the treatment of non-periodontal dental infections in adults or children in outpatient settings were included.ResultsFour publications reporting three RCTs comparing metronidazole with a β-lactam antibiotic were recovered. Studies were conducted in the 1970s–80s and aimed to demonstrate metronidazole was as effective as penicillin for the treatment of acute pericoronitis or acute apical infections with systemic involvement. Meta-analysis of results was not possible due to differences in measurement of infection signs. All studies concluded that metronidazole and penicillin are equally effective for the treatment of non-periodontal dental infections with systemic involvement.ConclusionsMetronidazole does not provide superior clinical outcomes (alone or in combination with a β-lactam) when compared with a β-lactam antibiotic alone for the treatment of non-periodontal dental infections in general dental practice. Guidelines should reinforce the importance of surgical interventions and if appropriate the use of a single agent narrow-spectrum β-lactam.

Pneumococcal urinary antigen testing for antimicrobial guidance in community-acquired pneumonia–A register-based cohort study

ObjectivesTo evaluate the effect of pneumococcal urinary antigen test (UAT) usage on broad-spectrum antibiotic treatment in community-acquired pneumonia (CAP). MethodsPatients admitted to 32 Swedish hospitals between 2011 and 2014 were retrospectively included from the Swedish National Quality Register of CAP. Using propensity score matched data, stratified by CRB-65 score, we studied the effect of performing UAT and of positive test results on treatment with broad-spectrum β-lactam monotherapy (BSBM) and antibiotics with coverage for atypical bacteria compared to narrow-spectrum β-lactam monotherapy (NSBM). ResultsUAT was performed for 4,995/14,590 (34.2%) patients, 603/4,995 (12.1%) of whom had positive test results. At day three, performing UAT was not associated with decreased use of BSBM (OR 1.07, 95% CI 0.94–1.23) but was associated with increased atypical coverage among patients with CRB-65 score 2 (OR 1.47, 95% CI 1.06–2.02). A positive UAT was associated with decreased BSBM use (OR 0.39, 95% CI 0.25–0.60) and decreased atypical coverage (OR 0.25, 95% CI 0.16–0.37), predominantly in non-severe CAP. At day one, performing UAT was associated with atypical coverage among patients with CRB-65 scores 2 (OR 2.60, 95% CI 1.69–3.98) and 3–4 (OR 3.69, 95% CI 1.55–8.79), and a positive test reduced the odds of BSBM treatment among CRB-65 score 3–4 patients (OR 3.49, 95% CI 1.02–12.0). ConclusionsPerforming UAT had no overall effect on decreasing the use of BSBM treatment by day three of hospitalization, yet non-severely ill patients with positive UAT results were less likely to be treated with BSBM and antibiotics with atypical coverage.

Risk of antibiotic treatment failure in premenopausal women with uncomplicated urinary tract infection.

Acute uncomplicated urinary tract infections (UTIs) are among the most common indications for antibiotic prescriptions in otherwise healthy women. We compared the risk of treatment failure of antibiotic regimens for outpatient treatment of UTI in real-world practice. We identified non-pregnant, premenopausal women diagnosed with uncomplicated, lower tract UTI and prescribed an oral antibiotic with activity against common uropathogens. We used propensity score-weighted Kaplan-Meier functions to estimate 30-day risks and risk differences (RD) for pyelonephritis and UTI-related antibiotic prescription switch. Of 1 140 602 patients, the distribution of index prescriptions was 44% fluoroquinolones (non-first-line), 28% trimethoprim-sulfamethoxazole (TMP/SMX) (first-line), 24% nitrofurantoin (first-line), 3% narrow-spectrum β-lactams (non-first-line), 1% broad-spectrum β-lactams (non-first-line), and 1% amoxicillin/ampicillin (non-recommended). Compared to the risk of pyelonephritis for nitrofurantoin (0.3%), risks were higher for TMP/SMX (RD, 0.2%; 95% CI, 0.2%-0.2%) and broad-spectrum β-lactams (RD, 0.2%; 95% CI, 0.1%-0.4%). Compared to the risk of prescription switch for nitrofurantoin (12.7%), the risk was higher for TMP/SMX (RD 1.6%; 95% CI 1.3%-1.7%) but similar for broad-spectrum β-lactams (RD -0.7%; 95% CI -1.4%-0.1%) and narrow-spectrum β-lactams (RD -0.3%; 95% CI -0.8%-0.2%). Subgroup analyses suggest TMP/SMX treatment failure may be due in part to increasing uropathogen resistance over time. The risk of treatment failure differed by antibiotic agent, with higher risk associated with TMP/SMX versus nitrofurantoin, and lower or similar risk associated with broad- versus narrow-spectrum β-lactams. Given serious safety warnings for fluoroquinolones, these results suggest that nitrofurantoin may be preferable as the first-line agent for outpatient treatment of uncomplicated UTI.

17. Comparative Safety of Antibiotic Therapy for Outpatient Treatment of Uncomplicated Urinary Tract Infections

BackgroundUrinary tract infection (UTI) is one of the most common indications for outpatient antibiotic prescriptions in otherwise healthy women, yet the comparative safety of antibiotics for empirical therapy is not well established. We compared the risk of adverse drug events by antibiotic treatment regimen among premenopausal women with uncomplicated UTI.MethodsUsing the IBM MarketScan Commercial Database (2006–2015), we identified healthy, non-pregnant women aged 18–44 who were diagnosed with UTI and prescribed a same-day antibiotic with activity against common uropathogens. Patients were followed for outcomes with varying follow-up periods: 3 days (anaphylaxis), 14 days (acute renal failure, skin rash, urticaria/hives, nausea/vomiting, abdominal pain), 30 days (vaginitis/vulvovaginal candidiasis, non-C. difficile diarrhea) and 90 days (C. difficile diarrhea, pneumonia, tendinopathy, retinal detachment). We estimated propensity score-weighted hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards models.ResultsOf 1,140,602 eligible women, the distribution of antibiotic receipt was fluoroquinolones (44%), trimethoprim-sulfamethoxazole (TMP/SMX) (28%), nitrofurantoin (24%), narrow-spectrum β-Lactam / β-Lactamase inhibitor combinations (“β-Lactams”) (3%), broad-spectrum β-Lactams (1%) and amoxicillin/ampicillin (1%). Of two first-line agents, we observed higher risk of outcomes among TMP/SMX vs. nitrofurantoin initiators: acute renal failure (HR 2.46, 95% CI 1.46–4.14), skin rash (HR 2.43, 95% CI 2.13–2.77), urticaria (HR 1.35, 95% CI 1.18–1.56), nausea/vomiting (HR 1.19, 95% CI 1.10–1.29) and abdominal pain (HR 1.14, 95% CI 1.09–1.19). Compared to nitrofurantoin, non-first-line agents (fluoroquinolones, broad-, and/or narrow-spectrum β-Lactams) were associated with higher risk of acute renal failure, skin rash, nausea/vomiting, abdominal pain, vaginitis/vulvovaginal candidiasis, diarrhea (C. difficile & non-C. difficile), pneumonia and tendinopathy.ConclusionThe risk of adverse drug events differs widely by antibiotic agent, with substantial differences in first-line agents. Understanding antibiotic safety is critical to prevent suboptimal antibiotic prescribing and reduce adverse events.Disclosures Margaret A. Olsen, PhD, MPH, Merck (Grant/Research Support)Pfizer (Consultant, Grant/Research Support)

The impact of a multimodel approach to designing a new orthopedic department.

To determine whether a multifaceted approach effectively influenced antibiotic use in an orthopedics department. Retrospective cohort study comparing the readmission rate and antibiotic use before and after an intervention. A 1,000-bed, tertiary-care, university hospital. Adult patients admitted to the orthopedics department between January 2015 and December 2018. During the preintervention period (2015-2016), 1 general orthopedic department was in operation. In the postintervention period (2017-2018), 2 separate departments were created: one designated for elective "clean" surgeries and another that included a "complicated wound" unit. A multifaceted strategy including infection prevention measures and introducing antibiotic stewardship practices was implemented. Admission rates, hand hygiene practice compliance, surgical site infections, and antibiotic treatment before versus after the intervention were analyzed. The number of admissions and hospitalization days in the 2 periods did not change. Seven-day readmissions per annual quarter decreased significantly from the preintervention period (median, 7 days; interquartile range [IQR], 6-9) to the postintervention period (median, 4 days; IQR, 2-7; P = .038). Hand hygiene compliance increased and surgical site infections decreased in the postintervention period. Although total antibiotic use was not reduced, there was a significant change in the breakdown of the different antibiotic classes used before and after the intervention: increased use of narrow-spectrum β-lactams (P < .001) and decreased use of β-lactamase inhibitors (P < .001), third-generation cephalosporins (P = .044), and clindamycin (P < .001). Restructuring the orthopedics department facilitated better infection prevention measures accompanied by antibiotic stewardship implementation, resulting in a decreased use of broad-spectrum antibiotics and a significant reduction in readmission rates.

Antibiotic utilization within 18 community hospitals in the United States: A 5-year analysis.

Antibiotic overuse is associated with antibiotic resistance. We evaluated antibiotic utilization defined by days of therapy/1000 patient days (DOT/1000 PD) in various community hospitals across the United States. Community hospitals within the Cardinal Health Drug Cost Opportunity Analytics database were evaluated for the availability of DOT/1000 PD data between 2012 to 2016 for overall and specific antibiotic use and the following classes: narrow-spectrum β-lactams (ampicillin, nafcillin, oxacillin, cefazolin, and cephalexin), non-carbapenem antipseudomonal β-lactams (piperacillin/tazobactam, ceftazidime, and cefepime), carbapenems, anti-methicillin-resistant Staphylococcus aureus agents (vancomycin, linezolid, daptomycin, and tigecycline), and fluoroquinolones. Antibiotic utilization and change in utilization during the study period was calculated using linear regression (β coefficient). Eighteen hospitals had antibiotic utilization data available. Hospitals were primarily urban (72%) with an average of 209 total beds and 22 intensive care unit beds. Mean number of pharmacists in these hospitals was nine with a mean pharmacist: bed ratio of 0.05. While all hospitals had antimicrobial stewardship programs established during the study period, only 78% and 22% had infectious diseases (ID) physician and ID pharmacist on staff, respectively. A decrease in antipseudomonal β-lactams (excluding carbapenems) and fluoroquinolones was observed (β coefficients = -1.2 and -2.6, respectively), all other antibiotic classes had increased utilization. Overall antibiotic utilization increased over 5 years. The increase in narrow-spectrum β-lactams utilization along with the reduction in the use of antipseudomonal β-lactams and fluoroquinolones indicate appropriate antimicrobial stewardship. Institutional antibiotic utilization should be evaluated for appropriateness to limit the overuse of broad-spectrum antibiotics in an effort to reduce resistance development.

Comparison of the effectiveness of penicillin and broad-spectrum β-lactam antibiotics in the treatment of community-acquired pneumonia in children

IntroductionBacterial community-acquired pneumonia (CAP) in children is caused mostly by Streptococcus pneumoniae. The resistance of pneumococci to penicillin is increasing. However, most guidelines still prefer treatment with narrow-spectrum antibiotics. Therefore, we compared the effect of intravenous treatment with penicillin and broad-spectrum β-lactam antibiotics in children with CAP. The objective of our study was to assess the eligibility of treatment of bacterial CAP with intravenous penicillin.Material and methodsWe performed a prospective study and included 136 children hospitalised because of bacterial CAP. Patients were treated intravenously with either penicillin G or broad-spectrum β-lactam antibiotic monotherapy. Lung ultrasound and blood tests were performed at admission and after 2 days of treatment. The time interval from the application of antibiotics to permanent defervescence was recorded.ResultsEighty-seven (64.0%) patients were treated with penicillin G, and 49 (36.0%) were treated with broad-spectrum β-lactam antibiotics. The median time to persistent defervescence was 5 h in the penicillin group and 8 h in the broad-spectrum group (p = 0.18). There were no significant differences between the treatment regimens regarding the effect on the consolidation sizes or C-reactive protein levels. However, the decrease in the white blood cell count was marginally greater in the penicillin treatment group (p = 0.05).ConclusionsWe have shown that penicillin is as effective as broad-spectrum antibiotics in the treatment of bacterial CAP in children. Although the resistance of pneumococci to antibiotics is increasing, clinicians should still use penicillin and other narrow-spectrum β-lactam antibiotics in the treatment of bacterial CAP in children.

Antibiotic Stewardship Implementation and Antibiotic Use at Hospitals With and Without On-site Infectious Disease Specialists.

Many US hospitals lack infectious disease (ID) specialists, which may hinder antibiotic stewardship efforts. We sought to compare patient-level antibiotic exposure at Veterans Health Administration (VHA) hospitals with and without an on-site ID specialist, defined as an ID physician and/or ID pharmacist. This retrospective VHA cohort included all acute-care patient admissions during 2016. A mandatory survey was used to identify hospitals' antibiotic stewardship processes and their access to an on-site ID specialist. Antibiotic use was quantified as days of therapy per days present and categorized based on National Healthcare Safety Network definitions. A negative binomial regression model with risk adjustment was used to determine the association between presence of an on-site ID specialist and antibiotic use at the level of patient admissions. Eighteen of 122 (14.8%) hospitals lacked an on-site ID specialist; there were 525 451 (95.8%) admissions at ID hospitals and 23 007 (4.2%) at non-ID sites. In the adjusted analysis, presence of an ID specialist was associated with lower total inpatient antibacterial use (odds ratio, 0.92; 95% confidence interval, .85-.99). Presence of an ID specialist was also associated with lower use of broad-spectrum antibacterials (0.61; .54-.70) and higher narrow-spectrum β-lactam use (1.43; 1.22-1.67). Total antibacterial exposure (inpatient plus postdischarge) was lower among patients at ID versus non-ID sites (0.92; .86-.99). Patients at hospitals with an ID specialist received antibiotics in a way more consistent with stewardship principles. The presence of an ID specialist may be important to effective antibiotic stewardship.

192. Augmenting Utility of Rapid Diagnostic Testing in Treatment of Gram-Negative Bacteremia with Stewardship Intervention

BackgroundRapid diagnostic tests (RDT) can identify pathogens in bloodstream infections (BSI) in less than 24 hours. Our institution utilizes an RDT for blood cultures (BCx) that can detect various organisms and resistance determinants. A retrospective evaluation conducted in our institution calculated the negative predictive values (NPV) of various Gram-negative pathogens and susceptibility to target antimicrobials in the absence of detected resistance markers. Resultant NPV >90% for E. coli and K. pneumoniae to ceftriaxone support use of RDT with stewardship intervention for more rapid de-escalation of antimicrobial therapy in patients with resistance marker-negative BSI.MethodsIn our facility, all positive BCx are processed through RDT. In the post-intervention group, pharmacists monitored RDT results and provided recommendations. Our IRB-approved, prospective study assessed time to antimicrobial de-escalation in treatment of resistance marker-negative E. coli and K. pneumoniae BSI before (January 1 to December 31, 2018) and after Stewardship intervention (January 1 to March 31, 2019). Secondary outcomes included days of therapy (DOT) of target narrow-spectrum β-lactams, carbapenems, and non-carbapenem anti-pseudomonal (NCAP) β-lactams, length of stay (LOS), and treatment failure. Data were analyzed using the Fisher exact or Chi-square and t-test for categorical and continuous data, respectively.ResultsOf the 12,893 evaluated RDT results in the pre-intervention group and 2,238 post intervention, 41 and 12 patients met inclusion criteria, respectively. Baseline characteristics were similar in both groups. Time to de-escalation to a target agent was decreased by 24 hours after stewardship intervention (50 v 74.6 hours) (P = 0.14). There were no statistically significant differences in DOTs for target agents (5.19 v 5.25 DOT; P = 0.48), carbapenems (1.29 v 1.08 DOT; P = 0.41), or NCAP β-lactams (1.73 v 2.33; P = 0.25). Treatment failure (2 in each group; P = 0.17) and LOS (10.9 v 11.9 days; P = 0.4) were similar between groups. Protocol compliance and intervention acceptance rate was approximately 60%.ConclusionAppreciation of NPVs and utilization of stewardship intervention allowed for early de-escalation of empiric therapy in patients with resistance marker-negative E. coli and K. pneumoniae bacteremia. Disclosures All authors: No reported disclosures.

Actinomyces Meyeri Empyema Necessitatis-A Case Report and Review of the Literature.

Pleural empyema necessitatis caused by Actinomyces meyeri is a rare but severe infection. A. species predominantly A. meyeri and A. israelii represent the second most common pathogen for empyema necessitans after mycobacteria. The incidence is reported in the literature to be 1:300,000. Men are thrice more likely to be affected than women. Pathogenetically, an infection can be triggered by aspiration in immunocompromised individuals which leads to an atelectasis with pneumonitis. In two cases, a 38-year-old construction worker and a 61-year-old woman with ulcerative breast carcinoma, who presented to the local emergency department with a painful swelling of the left chest, diagnostic workup revealed a pleural empyema necessitatis of the left chest. An antibiotic treatment was initiated with piperacillin/tazobactam and sulbactam/ampicillin, respectively. Temporally vacuum-dressing therapy was initiated after surgical debridement. In the course of the procedure, a reconstruction of tissue damage was feasible. The patients were recovered completely and discharged with an oral antibiotic treatment (amoxicillin) for 6 and 12 months, respectively. Thoracic actinomycosis is a relatively uncommon and traditionally chronic, indolent infection secondary to pulmonary infection with A. species . Surgical treatment is generally reserved for cases failing to resolve with antibiotic therapy. Early diagnosis, prompt debridement, and narrow spectrum β-lactam antibiotics can result in complete resolution of infection and good prognosis.

1787. The Safety and Efficacy of an Oral Penicillin Rechallenge Program in Cancer Patients: A Pilot Multicenter Study

BackgroundPatient-reported antibiotic allergies (so-called antibiotic allergy labels [AALs]) are found in one in four cancer patients and significantly impact patient outcomes. Whilst 85% of AALs can be removed by skin testing, the role of simple point-of-care oral penicillin rechallenge in this cohort remains unknown. We report on a novel penicillin rechallenge program in cancer patients.MethodsAn oral penicillin rechallenge program was implemented at Austin Health (Melb, Aus) and Peter MacCallum Cancer Centre (Melb, Aus) on May 31, 2017. Patients were prospectively identified by Infectious Diseases and antimicrobial stewardship (AMS) services at both sites and reviewed by the conjoint Antibiotic Allergy Service for suitability as per the criteria outlined in Figure 1. Patients underwent supervised challenge with oral penicillin VK 250 mg or amoxicillin 250 mg, dependent on reported index allergy, and observed for 2-hours post. Patients were followed for up to 12 months post for adverse events and antibiotic usage. Figure 1. Selection algorithm for oral penicillin rechallenge program.ResultsTwenty-nine patients underwent penicillin oral challenge between May 31, 2017 to April 30, 2018, 15 with cancer. Of those with cancer, 8 (53%) were male, median age 56 years (IQR 44, 67), 15 (100%) avoiding penicillin, and 7 (47%) penicillins and cephalosporins. The penicillin–amoxicillin AAL phenotypes were “rash” in 73% (11/15) and “unknown” in 27% (4/15). Patients were challenged with penicillin VK or amoxicillin, based on their reported penicillin allergy with no positive challenges or adverse events noted in those with (n = 15) and without (n = 14) cancer. In the follow-up period, 88% (14/16) patients that were prescribed antibiotics received a narrow-spectrum β-lactam.ConclusionA pilot penicillin oral rechallenge program was safe in cancer patients. This program serves as a future model for active “de-labelling” in carefully selected cancer patients, without formal allergy services, aiding AMS programs.Disclosures All authors: No reported disclosures.

Effectiveness of β-Lactam Monotherapy vs Macrolide Combination Therapy for Children Hospitalized with Pneumonia: Williams DJ, Edwards KM, Self WH, et al. JAMA Pediatr 2017;171(12):1184-1191

Pneumonia is among the top 3 reasons children are hospitalized in the United States and accounts for more antibiotic days in children's hospitals than any other condition. National guidelines recommend the use of narrow-spectrum β-lactam antibiotics for pediatric pneumonia with the addition of macrolides only when atypical bacterial infection is suspected. The evidence to support the routine addition of macrolides is conflicting but the combination is used empirically quite frequently.

Impact of an Integrated Antibiotic Allergy Testing Program on Antimicrobial Stewardship: A Multicenter Evaluation.

Despite the high prevalence of patient-reported antibiotic allergy (so-called antibiotic allergy labels [AALs]) and their impact on antibiotic prescribing, incorporation of antibiotic allergy testing (AAT) into antimicrobial stewardship (AMS) programs (AAT-AMS) is not widespread. We aimed to evaluate the impact of an AAT-AMS program on AAL prevalence, antibiotic usage, and appropriateness of prescribing. AAT-AMS was implemented at two large Australian hospitals during a 14-month period beginning May 2015. Baseline demographics, AAL history, age-adjusted Charlson comorbidity index, infection history, and antibiotic usage for 12 months prior to testing (pre-AAT-AMS) and 3 months following testing (post-AAT-AMS) were recorded for each participant. Study outcomes included the proportion of patients who were "de-labeled" of their AAL, spectrum of antibiotic courses pre- and post-AAT-AMS, and antibiotic appropriateness (using standard definitions). From the 118 antibiotic allergy-tested patients, 226 AALs were reported (mean, 1.91/patient), with 53.6% involving 1 or more penicillin class drug. AAT-AMS allowed AAL de-labeling in 98 (83%) patients-56% (55/98) with all AALs removed. Post-AAT, prescribing of narrow-spectrum penicillins was more likely (adjusted odds ratio [aOR], 2.81, 95% confidence interval [CI], 1.45-5.42), as was narrow-spectrum β-lactams (aOR, 3.54; 95% CI, 1.98-6.33), and appropriate antibiotics (aOR, 12.27; 95% CI, 5.00-30.09); and less likely for restricted antibiotics (aOR, 0.16; 95% CI, .09-.29), after adjusting for indication, Charlson comorbidity index, and care setting. An integrated AAT-AMS program was effective in both de-labeling of AALs and promotion of improved antibiotic usage and appropriateness, supporting the routine incorporation of AAT into AMS programs.

Antibiotic Utilization and Antimicrobial Stewardship in Community Hospitals

BackgroundOverthe use of antibiotics has been associated with the emergence of antibiotic resistance. This study aims to evaluate trends in antibiotic utilization as defined by days of therapy per 1000 patient-days (DOT/1000 PD) in various community hospitals across the US.MethodsEighteen network hospitals provided antibiotic utilization data (2012–2016) on overall antibiotic use and the following classes: narrow-spectrum β-lactams (ampicillin, nafcillin, oxacillin, cefazolin, and cephalexin), non-carbapenem antipseudomonal β-lactams (piperacillin/tazobactam, ceftazidime, and cefepime), carbapenems, anti-methicillin-resistant Staphylococcus aureus (MRSA) agents (vancomycin, linezolid, daptomycin, and tigecycline), and fluoroquinolones. Antibiotic utilization and change in utilization trend during the study period was calculated using linear regression (β coefficient).ResultsHospitals were primarily urban (72%) with an average of 209 total beds and 22 ICU beds. All hospitals have antimicrobial stewardship programs (ASPs) established during the study period. A decrease in antipseudomonal B-lactams and fluoroquinolones was observed during the study period, all other antibiotic classes had increased use (Table).ConclusionOverall antibiotic utilization increased over five years, particularly carbapenems and anti-MRSA agents with the highest utilization being reported with the latter. Efforts are needed to halt or decrease the use of these broad spectrum antimicrobials.Disclosures All authors: No reported disclosures. Antibiotic Class Mean Utilization (Range), DOT/1000 PD Mean β Coefficient All Antibiotics 62.3 (49.4–80.6)2.7 Narrow-spectrum β-lactams 122.8 (64.5–207.2)18 Antipseudomonal β-lactams * 129.6 (35–191.6)-1.2 Carbapenems 46.7 (145–82)2.7 Anti-MRSA 156.9 (84.7–272.3)5.5 Fluoroquinolones 151.9 (88.5–207.6)-2.6 *Excluding carbapenems

Early Life Antibiotic Exposure and Weight Development in Children

To examine the timing, frequency, and type of antibiotic exposure during the first 10years of life in association with (over)weight across this period in a cohort of 979 children. Within the Child, Parents and Health: Lifestyle and Genetic Constitution Birth Cohort Study, antibiotic exposure record was obtained from general practitioners. Anthropometric outcomes (age- and sex-standardized body mass index, weight and height z-scores, and overweight) were measured repeatedly at 7 time points during the first 10years of life. Generalized estimating equations method was used for statistical analysis. After adjusting for confounding factors, children exposed to one course of antibiotics compared with none in the first 6months of life had increased weight- (adjusted generalized estimating equations estimates [adjβ] 0.24; 95% CI 0.03-0.44) and height (adjβ 0.23; 95% CI 0.0002-0.46) z-scores; exposure to ≥2 courses during the second year of life was associated with both increased weight (adjβ 0.34; 95% CI 0.07-0.60), and height z-scores (adjβ 0.29; 95% CI -0.003 to 0.59). Exposure later in life was not associated with anthropometric outcomes. Associations with weight z-scores were mainly driven by exposure to broad- (≥2 courses: adjβ 0.11; 95% CI 0.003-0.22) and narrow-spectrum β-lactams (1 course: adjβ 0.18; 95% CI 0.005-0.35) during the follow-up period. Specific antibiotic used was not associated with body mass index z-scores and overweight. Repeated exposure to antibiotics early in life, especially β-lactam agents, is associated with increased weight and height. If causality of obesity can be established in future studies, this further highlights the need for restrictive antibiotic use and avoidance of prescriptions when there is minimal clinical benefit.

Randomized Trial of Rapid Multiplex Polymerase Chain Reaction-Based Blood Culture Identification and Susceptibility Testing.

The value of rapid, panel-based molecular diagnostics for positive blood culture bottles (BCBs) has not been rigorously assessed. We performed a prospective randomized controlled trial evaluating outcomes associated with rapid multiplex PCR (rmPCR) detection of bacteria, fungi, and resistance genes directly from positive BCBs. A total of 617 patients with positive BCBs underwent stratified randomization into 3 arms: standard BCB processing (control, n = 207), rmPCR reported with templated comments (rmPCR, n = 198), or rmPCR reported with templated comments and real-time audit and feedback of antimicrobial orders by an antimicrobial stewardship team (rmPCR/AS, n = 212). The primary outcome was antimicrobial therapy duration. Secondary outcomes were time to antimicrobial de-escalation or escalation, length of stay (LOS), mortality, and cost. Time from BCB Gram stain to microorganism identification was shorter in the intervention group (1.3 hours) vs control (22.3 hours) (P < .001). Compared to the control group, both intervention groups had decreased broad-spectrum piperacillin-tazobactam (control 56 hours, rmPCR 44 hours, rmPCR/AS 45 hours; P = .01) and increased narrow-spectrum β-lactam (control 42 hours, rmPCR 71 hours, rmPCR/AS 85 hours; P = .04) use, and less treatment of contaminants (control 25%, rmPCR 11%, rmPCR/AS 8%; P = .015). Time from Gram stain to appropriate antimicrobial de-escalation or escalation was shortest in the rmPCR/AS group (de-escalation: rmPCR/AS 21 hours, control 34 hours, rmPCR 38 hours, P < .001; escalation: rmPCR/AS 5 hours, control 24 hours, rmPCR 6 hours, P = .04). Groups did not differ in mortality, LOS, or cost. rmPCR reported with templated comments reduced treatment of contaminants and use of broad-spectrum antimicrobials. Addition of antimicrobial stewardship enhanced antimicrobial de-escalation. NCT01898208.