Definitive Antibiotic Therapy Research Articles

Efficacy of thermal analysis in the detection of bacterial strains in periprosthetic joint infections

In musculoskeletal surgery, joint and periprosthetic infections are rare but significant complications with a high risk of morbidity. Rapid diagnosis, surgical intervention and definitive antibiotic therapy are key factors to the success of the treatment and the recovery of former limb function. In addition to the current diagnostic procedures, there is a need to introduce new, therapy-centered diagnostic procedures in view of the increase in antibiotic resistance. In our current study, we set out to demonstrate the practical utility of differential scanning calorimetry and the isoperibolic calorimetry in diagnostics of joint and periprosthetic infections. We have shown significant differences among the different grade of arthritis. Under experimental conditions, synovial fluid samples were artificially superinfected with the most frequently occurring bacteria at a concentration of 103–105 CFU mL−1 and monitored in isothermal mode at 37 °C. The isoperibolic tests clearly showed a specific, concentration-dependent representative curve (duration of proliferation and its maximum rates) for each bacterial strain of the study. In our opinion, the different thermal analytical methods can be useful in the diagnosis of septic inflammatory processes and, in the rapid selection of definitive antibiotic therapy.

Variation in North American Infectious Disease Specialists' Practice Regarding Oral and Suppressive Antibiotics for Adult Osteoarticular Infections: Results of an Emerging Infections Network (EIN) Survey.

Osteoarticular infections (OAIs) are commonly treated with prolonged intravenous (IV) antimicrobials. The Oral versus Intravenous Antibiotics for Bone and Joint Infection (OVIVA) trial demonstrated that oral (PO) antibiotics are noninferior to IV antibiotics in the treatment of OAIs. We surveyed infectious disease (ID) physicians about their use of PO antibiotics in the treatment of OAIs. An Emerging Infection Network survey with 9 questions regarding antibiotic prescribing for the treatment of OAIs was sent to 1475 North American ID physicians. The questions were mostly multiple choice and focused on the use of definitive oral antibiotic therapy (defined as oral switch within 2 weeks of starting antibiotics) and chronic suppressive antibiotic therapy (SAT). Of the 413 physicians who reported treating OAIs, 91% used oral antibiotics at least sometimes and 31% used them as definitive therapy, most often for diabetic foot osteomyelitis and native joint septic arthritis. The oral antibiotics most frequently used for OAIs included trimethoprim-sulfamethoxazole, doxycycline/minocycline, and linezolid for Staphylococcus aureus, amoxicillin/cefadroxil/cephalexin for streptococci, and fluoroquinolones for gram-negative organisms. The most common rationales for not transitioning to oral antibiotics included nonsusceptible pathogens, comorbidities preventing therapeutic drug levels, and concerns about adherence. SAT use was variable but employed by a majority in most cases of periprosthetic joint infection managed with debridement and implant retention. North American ID physicians utilize oral antibiotics and SAT for the management of OAIs, although significant practice variation exists. Respondents voiced a need for updated guidelines.

Refractory Osteomyelitis in a Military Service Member Resolved With Adjunctive Hyperbaric Oxygen Therapy.

Refractory osteomyelitis is typically defined as a chronic infection that persists or recurs despite definitive surgical management and antibiotic therapy. Cases often involve complex wounds or fractures and can be challenging to treat, resulting in multiple courses of broad-spectrum antibiotic therapy and numerous surgeries over periods of months to years. Adjuncts to improve resolution of these complicated infections are sorely needed. Here, we describe the case of a 47-year-old active duty military member who sustained an open right ankle fracture during a skydiving accident that was subsequently complicated by refractory osteomyelitis. The patient failed more than three courses of combined medical and surgical management over a 9-month period before undergoing adjunctive hyperbaric oxygen therapy (HBOT), ultimately resulting in resolution of the infection. Adjunctive HBOT for treatment of conditions such as refractory osteomyelitis may be an underutilized resource in part because of a general paucity of high-quality data in the literature supporting its use, as well as a relative lack of availability of this resource. Nonetheless, the overall accumulating body of evidence indicates that the use of adjunctive HBOT in select patients with refractory osteomyelitis is safe and effective and further research may be warranted given its relevance and potential impact to military populations.

Prescription pattern of antibiotics in urinary tract infection based on antimicrobial susceptibility test at a tertiary care hospital

Introduction: Urinary tract infection is a common bacterial infection associated with significant morbidity, mortality, and financial burden. This study aimed to identify the causative bacteria, assess their antimicrobial susceptibility patterns and evaluate empirical and definitive antibiotic therapy for urinary tract infection. Methods: A hospital-based crosssectional study was conducted at the outpatient medicine department at a teaching hospital in Nepal from February 15 to July 14, 2022. Two hundred participants with positive urine cultures and antimicrobial susceptibility testing were included. The microorganism causing urinary tract infection and prescription pattern of antibiotics pre-and post-AST report were analyzed. Results: The majority of isolated pathogens were gram-negative bacteria (73%), with Escherichia coli being the most common (53.5%), followed by Staphylococcus aureus among gram-positive bacteria (14.5%). Female patients had a higher incidence of urinary tract infection (59.5%) than males (40.5%). The age group above 60 years had the highest occurrence (34%). Antibiotic susceptibility testing revealed that Escherechia coli exhibited higher sensitivity to nitrofurantoin, amikacin, and meropenem, while resistance was observed against ampicillin, cefixime, and norfloxacin. Empirical antibiotics were commonly prescribed, with levofloxacin and ceftriaxone being the most frequent choices. After antibiotic susceptibility testing, nitrofurantoin and levofloxacin were frequently prescribed. Conclusions: This study provides valuable insights into the etiology of urinary tract infection and antibiotic susceptibility patterns, aiding in selecting appropriate antimicrobial therapy based on local resistance patterns.

Clinical and molecular predictors of mortality in patients with carbapenem-resistant Acinetobacter baumannii bacteremia: A retrospective cohort study

Background/PurposeTo investigate the virulence profiles and identify clinical and microbiological predictors of mortality in patients with carbapenem-resistant Acinetobacter baumannii (A. baumannii) bacteremia. MethodsThis retrospective cohort study enrolled adult patients with carbapenem-resistant A. baumannii (CRAB). Multivariate logistic regression was used to identify the predictors of 30-day mortality. All isolates were subjected to real-time polymerase chain reaction for virulence factors and genotyped using multilocus sequence typing. ResultsAmong the 153 patients with CRAB bacteremia, 66 % received appropriate definitive antibiotic therapy. The in-hospital and 30-day mortality rates were 58.3 and 23.5 %, respectively. Ultimately, we enrolled 125 patients with CRAB bacteremia in the analysis, excluding early mortality cases. All CRAB isolates carried blaOXA-23 and blaOXA-51. The clinical strains belonged to 10 sequence types (STs), and the major genotypes were ST191, ST195, ST451, and ST784. The distribution of virulence factors included surface adhesion (Ata, 84.8 %; ChoP, 7.2 %), biofilm formation (OmpA, 76.8 %), killing of host cells (AbeD, 99.2 %), toxins (LipA, 99.2 %), and conjugation (BfmR, 90.4 %). In multivariate logistic regression analysis, hemodialysis due to acute kidney injury and moderate to severe thrombocytopenia were significant risk factors associated with 30-day mortality. However, microbiological factors were not significant predictors. ConclusionsClinical factors such as hemodialysis due to acute renal injury and moderate to severe thrombocytopenia have a greater influence on mortality in CRAB bacteremia compared with microbiological factors.

2789. Cefepime Versus Non-Cefepime/Non-Carbapenem Therapy for Blood Stream Infections Caused by Non-ESBL-Producing Serratia Marcescens: A Subgroup Analysis of The Carbapenem-Serratia Multicenter Retrospective Cohort Study

Abstract Background Serratia Marcescens causes serious infections. Carbapenems were prescribed due to the bacterium’s ability to develop inducible AmpC-mediated resistance. Recent IDSA guidance recommends ceftriaxone and in high-burden cases, cefepime. Evidence on the role of cefepime in the treatment of Serratia bacteremia is scarce. We aim to evaluate the outcomes of patients who received cefepime-containing empiric and/or definitive therapy (CFCT) to those receiving non-cefepime therapy (NCFCT). Methods This is a sub-analysis of a retrospective study of 7 Massachusetts acute care hospitals from January 1, 2015, to October 31, 2022. We included hospitalized adults (≥18 years) with Serratia Marcescens bacteremia. IRB approval was obtained. Demographics, clinical course characteristics, and choice of antibiotic therapy were collected. Primary outcome was 30-day mortality, and secondary outcome was composite antimicrobial failure (see Definitions in Table 1). Chi Square and Mann-Whitney U tests were computed using SPSS statistical package. Results The original Carbapenem-Serratia study had 73 out of 128 patients who met the inclusion criteria (Figure 1). The non-carbapenem group (n=56) was further studied for the purpose of this subanalysis and was divided into CFCT (n=15) and NCFCT (n=41). The two subgroups were similar in baseline comorbidities, severity measures, and sources of bacteremia (Table 1). Neither 30-day mortality nor the composite outcome of antimicrobial failure were significantly different with relative risks of 0.94 (95% CI 0.16 to 5.3, P=0.948) and 1.21 (95% CI 0.27 to 5.4, P=0.800), respectively. Study exclusion flow-chart with subanlaysis. ESBL phenotypically defined by ceftriaxone resistance (MIC <1). Characteristics and outcomes of patient with Serratia bacteremia treated with a cefepime versus non-cefepime nor carbapenem therapy regimen. * Immunocompromised patients are those receiving immunosuppressants, chemotherapy, or transplants, having HIV with CD4+ T cell count <200 cells/mm3, neutropenia with ANC < 500 cells/mm3, or corticosteroid use with prednisone or equivalent >10 mg for ≥ 14 days. † Hospital-acquired bacteremia is diagnosed when a positive blood culture obtained from patients hospitalized for 48 hours or longer. Healthcare-associated bacteremia was defined as a positive blood culture is obtained within 48 hours of hospital admission and the patient fulfills specific pre-defined criteria utilized in prior studies. Community-acquired bacteremia refers to positive a blood culture obtained within 48 hours after hospital admission in patients who do not fit the criteria for healthcare-associated infections. ‡ Deep seated complicated infection included Infective endocarditis, septic arthritis, osteomyelitis, or epidural abscess § Empiric antibiotic therapy: Antibiotics administered before antimicrobial susceptibility testing (AST) results, with a minimum 48-hour of uninterrupted duration and appropriate dosing. || Definitive antibiotic therapy (i.e., antibiotics administered after the AST results, also with a minimum of 48-hour duration). ¶ Duration of total definitive antibiotic therapy was counted from day of AST results until last day of definitive antimicrobial therapy. # Microbiological failure, microbiological relapse, in- hospital mortality, 30-day mortality, infection-related hospital readmission, or recurrent Serratia bateremia within 30 days. Microbiological failure refers to the growth of Serratia after 48 hours of definitive antibiotic therapy, while microbiological relapse is the regrowth of Serratia after a negative blood culture (Kunz Coyne et al., 2023). Note: Two patients had recurrence of Serratia bacteremia within 30 days, neither were resistant to third generation cephalosporins. Δ Infection-related re-admission was defined when a patient is readmitted not solely for a procedure or surgery, and they experience fever, worsening leukocytosis, or required escalation of antimicrobial therapy from the definitive therapy of the index admission. Conclusion Averting cefepime in the antimicrobial therapy of Serratia bacteremia is not associated with a significant increase in 30-day mortality or the composite outcome of antimicrobial failure. When applicable, a narrower beta-lactam therapy such as ceftriaxone may be appropriate. Limitations include a small sample size, with higher risk for type II error, and overlap in definitive antibiotic therapy. Further prospective studies are needed to confirm these findings, especially in patients with deep-seated infections. Disclosures All Authors: No reported disclosures

2843. Risk Factors for Unplanned Healthcare Encounters in Patients Discharged from the Emergency Department with Extended-spectrum β-lactamase Urinary Tract Infections

Abstract Background The management of extended spectrum β-lactamase (ESBL) urinary tract infections (UTIs) in the emergency department (ED) has not been well documented in literature. The purpose of this study was to describe treatment and outcomes of patients with ESBL UTIs in the ED, which can inform best practices for antimicrobial stewardship. Methods This IRB approved, retrospective cohort analysis included patients who were discharged from the ED with an ESBL UTI between January 2020 and November 2022. The primary outcome of interest was any unplanned healthcare encounter related to the UTI within 30 days of the index ED visit, which included phone/virtual visits, clinic visits, ED visits, and hospitalizations. Patients ≥18 years of age treated for symptomatic UTI with a monomicrobial urine culture were included, while those with altered mental status, history of renal transplant, abnormal urinary tract, or were on active antibiotic therapy prior to the ED visit were excluded. Patient characteristics, initial and definitive antibiotic therapy, culture results including pathogen and susceptibilities were described. Logistic regression analysis was used to identify any exposures that were independently associated with unplanned healthcare encounters related to the UTI. Results 162 patients were included; 103 (64%) had an unplanned healthcare encounter. Patient characteristics are depicted in Table 1. Complicated lower UTI was most frequent occuring in 71 patients (44%). Susceptibility data revealed that nitrofurantoin was effective in 121 (75%) patients, aminoglycosides in 117 (72%) patients, TMP/SMX in 66 (41%) patients, and quinolones in 62 (38%) patients. 76 (74%) patients with unplanned encounters received an inactive empiric prescription: β-lactams being prescribed to 52 (51%) patients with cephalexin used for 49/52 (94%). Of the 81 patients with lower UTI, 20 (25%) initially received a prescription for nitrofurantoin. Factors associated with an unplanned healthcare encounter are described in Table 2.Table 2.Factors Associated with Unplanned Healthcare Encounters. Abbreviations: Un-Adj OR = unadjusted odds ratio; Adj OD = adjusted odds ratio Conclusion Patients discharged from the ED with an ESBL UTI were at higher risk for unplanned healthcare encounters if they had CKD or were initially prescribed an oral β-lactam. Prescribing first line therapy with nitrofurantoin for lower UTI is a potential area for improvement. Disclosures Michael Veve, PharmD, MPH, National Institutes of Health: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support

Neonatal Gut Microbiome Composition and Gut-Derived Bloodstream Infections in a Cohort of Premature Singaporean Infants

Abstract Background Due to their gestational age, low birth weight, and immature gut barriers, premature neonates are at high risk of bloodstream infections (BSI) caused by bacteria that reside in the gastrointestinal tract. Relatively little is known about the effect of alterations to the gut microbiota on the risk of BSI in premature neonates. Methods This prospective cohort study was conducted in the neonatal intensive care unit in the KK Women’s and Children’s Hospital in Singapore between June 1, 2019 and May 31, 2021. Clinical data and twice weekly fecal samples were collected during the first 75 days of life from infants born at or below 30 weeks gestational age. All infants received a Bifidobacterium breve probiotic starting at median (interquartile range [IQR]) day of life (DOL) 2 (1, 3). Fecal samples underwent shotgun metagenomic sequencing, and the resulting reads were aligned to Kraken 2 for taxonomic classification. We utilized permutational multivariate analysis of variance (PERMANOVA) and mixed effects linear regression to evaluate associations between clinical factors and gut microbiota composition. We described gut microbiota alterations among a subset of infants who developed a BSI. Results We collected 581 fecal samples from 75 neonates. Median (IQR) gestational age was 27 (25, 29) weeks and birthweight was 955 (763, 1210) grams. There were 18 BSIs that occurred among these infants and were caused by Streptococcus agalactiae (n=5), Klebsiella pneumoniae (n=3), Escherichia coli (n=2), Staphylococcus aureus (n=2), Staphylococcus epidermidis (n=2), Proteus mirabilis (n=1), Acinetobacter baumannii (n=1), Streptococcus anginosus (n=1), and Streptococcus pasteurianus (n=1). Metagenomic sequencing generated a median (IQR) sequencing depth of 5.9M (4.4M, 34.9M) paired-end reads per sample. The clinical factors that accounted for the most variance in gut microbiota composition were DOL (PERMANOVA; R2=0.022, p=0.001), feeding modality (R2=0.020, p=0.001), and antibiotic exposure (R2=0.018, p=0.001). Probiotic exposure was associated with an increase in the probiotic species, B. breve, and also a decrease in the relative abundances of several Clostridia species. Broad spectrum antibiotic exposures were associated with lower relative abundances of both potential pathogens, e.g., bacteria from the genera Enterobacter, Klebsiella, and Enterococcus, and beneficial bacteria, e.g., Bifidobacteria species, including the probiotic species. Notably, metronidazole and carbapenem exposures were associated with an increase in Staphylococcus species. Of 18 neonates who developed BSI, the causative species was detected in the gut microbiota of 17 infants. The relative abundance of the BSI species was ≥50% immediately prior to or at the time of BSI in 9 (50%) infants (Figure). Interestingly, four (22%) infants had a continued high abundance of the BSI species in the gut microbiota despite definitive antibiotic therapy. Conclusion Several clinical factors contribute to the gut microbiota composition of premature Singaporean neonates, especially postnatal age, feeding modality, and antibiotic exposures. Broad-spectrum antibiotic exposures affected the relative abundance of the probiotic agent and were associated with increases in staphylococcal species known to be potentially pathogenic in neonates. If detected in the gut microbiota, the bacteria that caused the BSI was often present in significant relative abundances both before and after the BSI. Figure. Relative abundances of bacterial species in the gut microbiota before and after bloodstream infections (BSI) in a subset of premature neonates. The relative abundances of the BSI species are plotted in color, whereas relative abundances of other detected species are depicted in gray. Each darkened vertical bar corresponds to a single fecal sample. Shading between each bar is provided to visualize changes in relative abundance between fecal samples. Black vertical lines depict the day of BSI. Specific antibiotic exposures are shown in the colored horizontal bars atop each subject’s time-series plot.

Antibiotic Therapy for Pneumonia in the Neonatal Intensive Care Unit: Is 5 Days Enough?

Abstract Background Antibiotic therapy provided to infants in the NICU is associated with both short-and-long-term adverse consequences. In 2019, the Neonatal Antimicrobial Stewardship Program (NEO-ASP) at Nationwide Children’s Hospital (NCH), Columbus, OH, recommended a five-day antibiotic course with a time-out for treatment of pneumonia in the seven NCH network NICUs. Objective To determine the duration of antibiotic therapy for pneumonia after implementation of a 5-day antibiotic treatment course and describe its safety among infants in the NICU. Methods Prospective surveillance of antibiotic therapy provided to infants in 7 NCH NICUs (1, level 4; 5, Level 3; 1, level 2) who were diagnosed with pneumonia by the attending neonatologist based on clinical and radiographic abnormalities from 8/2020 to 4/2022. Pertinent clinical, laboratory, and microbiologic data were obtained from electronic health records. Infants were excluded if they had positive bacterial cultures of blood, urine, or cerebrospinal fluid. The length of therapy (LOT) was defined as any calendar day that the infant received ≥1 antibiotic while definitive treatment course was the duration of appropriate antibiotic therapy. Safety was defined a priori by re-initiation of antibiotic therapy within 14 days after discontinuation of the initial treatment and/or mortality (overall/sepsis-related). Results From 8/2020 to 4/2022, NICU infants (66% male) were diagnosed with 136 episodes of pneumonia at a median (IQR) age of 2 (1-20) days. 61 (45%) of episodes were late onset at ≥3 days of age. All infants had sterile cultures of blood, urine, and cerebrospinal fluid, if performed. Their median (IQR) birth weight and gestational age were 2780 (1090-3450) g and 36 (28-38) wk, respectively. At the time of pneumonia diagnosis, 44% of infants were receiving CPAP while 55% were on mechanical ventilation (11% high frequency oscillatory ventilation). The median (IQR) LOT was 6 (5-6) days and length of definitive treatment was 5 (5-5) days. Overall mortality was 5% (7/128) with 2% of deaths being sepsis-related (n=3; Table 1). The majority of pneumonia episodes (88%; n=120) were treated with 5 days of definitive antibiotic therapy and 22 (16%) episodes had antibiotics restarted within 14 days (Table 1). There was no significant difference in the composite safety outcome between ≤5 vs. 6-20 days of definitive antibiotic therapy (p=0.29). Table 1. Safety assessments of definitive antibiotic treatment for 136 pneumonia episodes in 128 infants Table 2. Underlying conditions, antibiotic duration, and cause of death among 7 infants in the NICU Conclusion(s) There was excellent adherence (88%) to the NEO-ASP recommendation of a 5-day definitive treatment course for pneumonia and in addition, the intervention seemed safe.

The Impact of Antimicrobial Stewardship in Treating Patients with Escherichia coli Bacteremia in a Small Single Center Community Hospital.

Purpose: There are many challenges that pharmacist led antimicrobial stewardship programs can encounter including lack of resources, costs, and inaccurate antimicrobial susceptibility testing (AST) results. The COVID-19 pandemic has led to increased resistance especially with gram negative infections. At a small single center community hospital, gram negative infections, particularly Escherichia coli infections, predominately occur. Therefore, this study aims to address gram negative bacteremia burden and its impact on antimicrobial stewardship efforts for combatting Escherichia coli and ESBL organisms with such barriers during the pandemic. Methods: In a retrospective cohort study, patients ≥ 18 years of age from a small community hospital were reviewed. Patients were excluded if their blood cultures were not positive for Escherichia coli and if antibiotics were not initiated during hospital stay. The primary endpoint was to determine the length of hospital stay. Critical secondary endpoints include antibiotic de-escalations, duration of antibiotics, time to definitive antibiotic therapy, serum procalcitonin levels, blood culture availabilities, MIC breakpoints, co-infection of COVID-19, and Clostridioides difficile occurrences. Results: Out of 74 patients with gram negative bacteremia, 41 patients specifically had Escherichia coli bacteremia. The primary endpoint results showed that patients with Escherichia coli bacteremia that stayed in the ICU had a length of stay of 13.6 days. Patients with Escherichia coli bacteremia in the Non-ICU setting has a length of stay of 7.3 days, and patients with ESBL bacteremia in the Non-ICU setting had a length of stay of 6.8 days. Conclusions: Despite the various challenges that antimicrobial stewardship programs (ASP) face in a single center small community hospital, the ASP at this small community hospital utilizes various policies and tools to increase appropriate antibiotic use and decrease hospital length of stay in patients with Escherichia coli bacteremia.

Risk Factors for Recurrence of Community-Onset Urinary Tract Infections Caused by Extended-Spectrum Cephalosporin-Resistant Enterobacterales.

Extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) are an increasingly important cause of community-onset urinary tract infections (UTIs), including recurrent infections. We evaluated risk factors for recurrence among patients with community-onset ESCrE UTI. This retrospective cohort study included adults with community-onset ESCrE UTI in the Duke University Health System from April 2018 through December 2021. ESCrE UTI recurrence by the same species was assessed 14-180 days (ie, 6 months) after completion of antibiotic treatment. We evaluated the relationships between candidate risk factors and time to recurrence using Cox proportional hazards regression models. Among 1347 patients with community-onset ESCrE UTI, 202 (15.0%) experienced recurrent infection during the 6-month follow-up period. Independent risk factors for recurrence included neurogenic bladder (adjusted hazard ratio [aHR], 1.8 [95% confidence interval {CI}, 1.2-2.6]; P = .005), prior history of UTI (aHR, 2.4 [95% CI, 1.7-3.3]; P < .001), and fluoroquinolone nonsusceptibility of the index UTI (aHR, 1.5 [95% CI, 1.1-2.1]; P = .02). Klebsiella pneumoniae infection was associated with recurrence in univariate analysis (HR, 1.6 [95% CI, 1.1-2.1]; P = .007) but not multivariate analysis (aHR, 1.4 [95% CI, 1.0-1.9]; P = .06). Inappropriate initial or definitive antibiotic therapy was not predictive of ESCrE UTI recurrence. Recurrence of community-onset ESCrE UTI was common and associated with several patient and pathogen-level risk factors. Future studies should evaluate microbial risk factors for recurrence and improve the management of ESCrE UTI.

Cefoxitin versus carbapenems as definitive treatment for extended-spectrum β-lactamase-producing Klebsiella pneumoniae bacteremia in intensive care unit: a propensity-matched retrospective analysis.

Despite cefoxitin's in vitro resistance to hydrolysis by extended-spectrum beta-lactamases (ESBL), treatment of ESBL-producing Klebsiella pneumoniae (KP) infections with cefoxitin remains controversial. The aim of our study was to compare the clinical efficacy of cefoxitin as definitive antibiotic therapy for patients with ESBL-KP bacteremia in intensive care unit, versus carbapenem therapy. This retrospective study included all patients with monomicrobial bacteremia hospitalized in intensive care unit between January 2013 and January 2023 at the University Hospital of Guadeloupe. The primary outcome was the 30-day clinical success defined as a composite endpoint: 30-day survival, absence of relapse and no change of antibiotic therapy. Cox regression including a propensity score (PS) and PS-based matched analysis were performed for endpoint analysis. A total of 110 patients with bloodstream infections were enrolled. Sixty-three patients (57%) received definitive antibiotic therapy with cefoxitin, while forty-seven (43%) were treated with carbapenems. 30-day clinical success was not significantly different between patients treated with cefoxitin (57%) and carbapenems (53%, p = 0.823). PS-adjusted and PS-matched analysis confirmed these findings. Change of definitive antibiotic therapy was more frequent in the cefoxitin group (17% vs. 0%, p = 0.002). No significant differences were observed for the other secondary endpoints. The acquisition of carbapenem-resistant Pseudomonas aeruginosa was significantly higher in patients receiving carbapenem therapy (5% vs. 23%, p = 0.007). Our results suggest that cefoxitin as definitive antibiotic therapy could be a therapeutic option for some ESBL-KP bacteremia, sparing carbapenems and reducing the selection of carbapenem-resistant Pseudomonas aeruginosa strains.

Extensive Sequestration Chronic Maxillary Osteomyelitis in an Uncontrolled Diabetic Patient: Comprehensive Case Management of a Rare Entity.

The hallmark of osteomyelitis was progressive bone destruction and sequestrum formation. In the underlying disease, like diabetes mellitus, osteomyelitis becomes severe and exacerbates the condition. It was essential for the oral and maxillofacial surgeon to comprehend its complex medical and surgical management to achieve complete disease eradication. The aim of this article was to report a rare case and comprehensive management of extensive sequestrating maxillary osteomyelitis with uncontrolled diabetes mellitus patients. A 58-year-old male patient with pain and swelling accompanied by discharge of pus in the sinistra maxilla region. The systemic disease was identified as uncontrolled diabetes mellitus, and had a history of unhealing wounds 1 year ago after upper left molar extraction. Computed tomography scan result showed extensive sequester formation and bony destruction in the right extending to the left maxilla. Microbial culture results were Klebsiella pneumoniae and Morganella morganii. Subsequently, extensive sequestrectomy and multiple extractions of the involved jaw and teeth were performed after diabetes mellitus was regulated. A suspension suture against oral and nasal mucosa was performed to avoid dead space formation. Comprehensive perioperative management in maxillary osteomyelitis in uncontrolled diabetes mellitus includes sequestrectomy, definitive antibiotic therapy based on culture results, and diabetes regulation to improve the successful management of this case.

Clinical outcomes in elderly patients with infections caused by NDM-producing Klebsiella pneumoniae: results from a real-life retrospective single center study in an endemic area.

Real-life outcomes data for elderly patients with infections caused by Klebsiella pneumoniae producing New Delhi metallo-beta-lactamase (NDM-Kp) are lacking. We conducted a retrospective cohort study enrolling 33 consecutive adult patients (mean age 77.4years; 48.5% males; mean Charlson Comorbidity Index-CCI 5.9) hospitalized for NDM-Kp infections during a 24-month period in an Italian highly endemic area. 78.8% were admitted to Internal Medicine ward. 45.4% of patients had bloodstream infections (BSI), 39.4% urinary tract infections (UTI) without BSI, 9.1% respiratory tract infections and 6.1% intra-abdominal infections. 93.9% had rectal colonization.Adequate definitive antibiotic therapy (mainly represented by aztreonam plus ceftazidime/avibactam) was provided to 36.4% of cases. Mean age and CCI of patients adequately treated were significantly lower than those inadequately treated (71.2 vs 80.9years, p = 0.041, and 4.6 vs 6.7, p = 0.040, respectively). Patients adequately treated had a mean hospitalization length significantly higher (28 vs 15days, p = 0.016). The overall 30-day survival rate of patients adequately and inadequately treated was 83.3% and 57.1%, respectively: this difference was not statistically significant. Mean age and CCI of 22 patients who survived at 30days were lower than those of 11 patients who died (73.7 vs 84.8years, p = 0.003, and 5.3 vs 7.2, p = 0.049, respectively). Twelve survivors received an inadequate therapy: 8/12 had UTI. Six of nine patients inadequately treated who died within 30days, died before microbiological diagnosis. Our study provides real-life data on outcomes of elderly and multimorbid patients hospitalized for infections caused by NDM-Kp. Further studies with larger sample size are warranted.

Short-course antibiotic therapy for pneumonia in the neonatal intensive care unit.

To determine the adherence and safety outcomes of a 5-day antibiotic course with a "time-out" for treatment of "blood culture-negative" pneumonia in the NICU. Prospective surveillance of all infants diagnosed with pneumonia at 7 NICUs from 8/2020-12/2021. Safety outcomes were defined a priori by re-initiation of antibiotic therapy within 14 days after discontinuation and overall and sepsis-related mortality. 128 infants were diagnosed with 136 episodes of pneumonia; 88% (n = 119) were treated with 5 days of definitive antibiotic therapy. Antibiotics were restarted within 14 days in 22 (16%) of the 136 pneumonia episodes. However, only 3 (3%) of the 119 episodes of pneumonia treated for 5 days had antibiotics restarted for pneumonia. Mortality was 5% (7/128); 5 of the 7 deaths were assessed as sepsis-related. Adherence to the 5-day definitive antibiotic treatment for "culture-negative" pneumonia was high and the intervention seemed safe.

Fear of missing organisms (FOMO): Diabetic foot and osteomyelitis management opportunities

Background: Hospitalizations for diabetic foot infections and lower-extremity osteomyelitis are common. Use of empiric antibiotic therapy for methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa is also common. Guidelines recommend antibiotic therapy based on severity of illness, risk factors for MRSA and P. aeruginosa, and local prevalence. We evaluated the concordance between empiric antibiotic therapy and both culture results and definitive antibiotic therapy with a focus on MRSA and P. aeruginosa. We also evaluated how well MRSA and pseudomonal risk factors were predictive of culture results with these organisms. Methods: We conducted a cohort study of all patients admitted to our hospital system in 2021 with a diagnosis of a diabetic foot infection or lower-extremity osteomyelitis. Patients were included if they had an International Classification of Disease, Tenth Revision (ICD-10) diagnosis code of M86, E10.621, E11.621, or E08.621. Patients were excluded if antibiotics were for another indication or if they were aged &lt;18 years. In patients with multiple hospitalizations only the first hospitalization was included. Empiric antibiotic therapy included antibiotics started by the admitting team. Definitive antibiotic therapy included the final antibiotic course either completed during admission or prescribed at the time of discharge. MRSA risk factors included prior positive culture with MRSA within the last year, hospitalization with IV antibiotics within 90 days, intravenous drug use, or hemodialysis. Pseudomonal risk factors included prior positive culture with P. aeruginosa within the last year or hospitalization with IV antibiotics within 90 days. Results: In 2021, 260 unique patients were admitted with suspected diabetic foot infections or lower-extremity osteomyelitis. 68 patients had &gt;1 admission. Empiric anti-MRSA and antipseudomonal therapy was administered to 224 (86%) and 214 (82%) patients, respectively. Definitive anti-MRSA and antipseudomonal therapy was administered to 76 (30%) and 51 (20%) patients, respectively. Of the 195 patients who had wound cultures, 29 (15%) and 18 (9%) had positive cultures for MRSA and P. aeruginosa respectively (Fig.). The negative predictive value of MRSA risk factors for predicting a negative culture with MRSA was 91%. The negative predictive value of pseudomonal risk factors for predicting a negative culture with P. aeruginosa was 95%. Conclusions: Our data suggest an opportunity for substantial reductions in empiric anti-MRSA and antipseudomonal therapy for diabetic foot infection and lower-extremity osteomyelitis. The absence of MRSA and pseudomonal risk factors was reasonably good at predicting the absence of a positive culture with these organisms.Disclosure: None

Comparison of Oral and Intravenous Definitive Antibiotic Therapy for Beta-Hemolytic Streptococcus Species Bloodstream Infections from Soft Tissue Sources: a Propensity Score-Matched Analysis.

Beta-hemolytic streptococci are common causes of bloodstream infection (BSI). There is emerging data regarding oral antibiotics for BSI but limited for beta-hemolytic streptococcal BSI. We conducted a retrospective study of adults with beta-hemolytic streptococcal BSI from a primary skin/soft tissue source from 2015 to 2020. Patients transitioned to oral antibiotics within 7 days of treatment initiation were compared to those who continued intravenous therapy, after propensity score matching. The primary outcome was 30-day treatment failure (composite of mortality, infection relapse, and hospital readmission). A prespecified 10% noninferiority margin was used for the primary outcome. We identified 66 matched pairs of patients treated with oral and intravenous antibiotics as definitive therapy. Based on an absolute difference in 30-day treatment failure of 13.6% (95% confidence interval 2.4 to 24.8%), the noninferiority of oral therapy was not confirmed (P = 0.741); on the contrary, the superiority of intravenous antibiotics is suggested by this difference. Acute kidney injury occurred in two patients who received intravenous treatment and zero who received oral therapy. No patients experienced deep vein thrombosis or other vascular complications related to treatment. In patients treated for beta-hemolytic streptococcal BSI, those who transitioned to oral antibiotics by day 7 showed higher rates of 30-day treatment failure than propensity-matched patients. This difference may have been driven by underdosing of oral therapy. Further investigation into optimal antibiotic choice, route, and dosing for definitive therapy of BSI is needed.

Effectiveness of third-generation cephalosporins or piperacillin compared with cefepime or carbapenems for severe infections caused by wild-type AmpC β-lactamase-producing Enterobacterales: A multi-centre retrospective propensity-weighted study

The optimal treatment regimen for infections caused by wild-type AmpC β-lactamase-producing Enterobacterales remains controversial. This study compared the outcomes of bloodstream infections (BSI) and pneumonia according to the type of definitive antibiotic therapy: third-generation cephalosporin (3GC), piperacillin ± tazobactam, cefepime or carbapenem. All cases of BSI and pneumonia caused by wild-type AmpC β-lactamase-producing Enterobacterales over 2 years in eight university hospitals were reviewed. Patients who received definitive therapy consisting of either a 3GC (3GC group), piperacillin ± tazobactam (piperacillin group), or cefepime or a carbapenem (reference group) were included in this study. The primary endpoint was 30-day all-cause mortality. The secondary endpoint was treatment failure due to infection by emerging AmpC-overproducing strains. Propensity-score-based models were used to balance confounding factors between groups. In total, 575 patients were included in this study: 302 (52%) with pneumonia and 273 (48%) with BSI. Half (n=271, 47%) received cefepime or a carbapenem as definitive therapy, 120 (21%) received a 3GC, and 184 (32%) received piperacillin ± tazobactam. Compared with the reference group, 30-day mortality was similar in the 3GC [adjusted hazard ratio (aHR) 0.86, 95% confidence interval (CI) 0.57-1.31)] and piperacillin (aHR 1.20, 95% CI 0.86-1.66) groups. The likelihood of treatment failure was higher in the 3GC (aHR 6.81, 95% CI 3.76-12.4) and piperacillin (aHR 3.13, 95% CI 1.69-5.80) groups. The results were similar when stratifying the analysis on pneumonia or BSI. Treatment of included BSI or pneumonia caused by wild-type AmpC β-lactamase-producing Enterobacterales with 3GC or piperacillin ± tazobactam was not associated with higher mortality, but was associated with increased risk of AmpC overproduction leading to treatment failure compared with cefepime or a carbapenem.

Application of a sepsis flow chip (SFC) assay for the molecular diagnosis of paediatric sepsis.

A delay in detecting sepsis pathogens is a problematic issue for determining definitive antibiotic therapy for the causative pathogens. The gold standard method for sepsis is blood culture but this requires 3 days to detect the definitive pathogen. Molecular methods offer rapid identification of pathogens. We evaluated the use of sepsis flow chip (SFC) assay for identifying pathogens from children with sepsis. Blood samples from children with sepsis were collected and incubated in a culture device. Positive samples were subjected to amplification-hybridization using SFC assay and culture. A total of 94 samples from 47 patients were recovered, from which 25 isolates were recovered, including Klebsiella pneumoniae (11) and Staphylococcus epidermidis (6). From 25 positive blood culture bottles subjected to SFC assay, 24 genus/species and 18 resistance genes were detected. The sensitivity, specificity and conformity was 80, 94.2 and 94.68 % respectively. SFC assay offers promise to identify pathogens from positive blood culture in paediatric patients with sepsis and may support the antimicrobial stewardship programme in hospitals.

No more tears from surgical site infections in interventional pain management.

As the field of interventional pain management (IPM) grows, the risk of surgical site infections (SSIs) is increasing. SSI is defined as an infection of the incision or organ/space that occurs within one month after operation or three months after implantation. It is also common to find patients with suspected infection in an outpatient clinic. The most frequent IPM procedures are performed in the spine. Even though primary pyogenic spondylodiscitis via hematogenous spread is the most common type among spinal infections, secondary spinal infections from direct inoculation should be monitored after IPM procedures. Various preventive guidelines for SSI have been published. Cefazolin, followed by vancomycin, is the most commonly used surgical antibiotic prophylaxis in IPM. Diagnosis of SSI is confirmed by purulent discharge, isolation of causative organisms, pain/tenderness, swelling, redness, or heat, or diagnosis by a surgeon or attending physician. Inflammatory markers include traditional (C-reactive protein, erythrocyte sedimentation rate, and white blood cell count) and novel (procalcitonin, serum amyloid A, and presepsin) markers. Empirical antibiotic therapy is defined as the initial administration of antibiotics within at least 24 hours prior to the results of blood culture and antibiotic susceptibility testing. Definitive antibiotic therapy is initiated based on the above culture and testing. Combination antibiotic therapy for multidrug-resistant Gram-negative bacteria infections appears to be superior to monotherapy in mortality with the risk of increasing antibiotic resistance rates. The never-ending war between bacterial resistance and new antibiotics is continuing. This article reviews prevention, diagnosis, and treatment of infection in pain medicine.