Initial Antimicrobial Therapy Research Articles

Clinical Predictors of Bacteremia Outcome After Initial Empirical Antimicrobial Therapy in Patients with Hematological Malignancies: A Retrospective Analysis

Clinical Predictors of Bacteremia Outcome After Initial Empirical Antimicrobial Therapy in Patients with Hematological Malignancies: A Retrospective Analysis

To treat or not to treat: Assessing the role of anti-enterococcal therapy for intra-abdominal infections in patients with cancer.

The clinical significance of enterococci in intra-abdominal infections, particularly those caused by multiple organisms, remains unclear. There are no definitive guidelines regarding the use of empiric therapy with antimicrobial agents targeting enterococci. In this study, we evaluated the impact of the initial antimicrobial therapy administration of anti-enterococcal agents on the treatment of intra-abdominal infections in patients with cancer in whom enterococci were isolated from ascitic fluid cultures. This retrospective study was conducted at Shizuoka Cancer Center between January 1, 2014, and December 31, 2020, on all adult patients with cancer with enterococci in their ascitic fluid cultures. The primary outcome was all-cause mortality, and the secondary outcomes were composite outcomes consisting of three components (mortality, recurrence, and treatment failure) and the risk factors associated with all-cause mortality and composite outcomes. In total, 103 patients were included: 61 received treatment covering enterococci, and 42 did not. The mortality rates did not differ significantly between the treated and untreated groups (treated: 8/61 [13.1%]; untreated: 5/42 [11.9%]; p = 1.00). Additionally, no significant difference was observed between the groups in terms of composite outcomes (treated group: 11/61 [18.0%]; untreated group: 9/42 [21.4%]; p = 0.80). Multivariate analysis showed that performance status (PS2-4; p < 0.0001) was an independent risk factor for mortality. The composite outcome was also significantly higher for PS2-4 (p = 0.007). Anti-enterococcal treatment was not associated with mortality or the composite outcome. In patients with cancer and intra-abdominal infections caused by enterococci, anti-enterococcal therapy was not associated with prognosis, whereas PS2 or higher was associated with prognosis. The results of this study suggest that the initial routine administration of anti-enterococcal agents for intra-abdominal infections may not be essential for all patients with cancer. To substantiate these findings, validation by a prospective randomized trial is warranted.

Acidic Urine pH and Clinical Outcome of Lower Urinary Tract Infection in Kidney Transplant Recipients Treated with Ciprofloxacin and Fosfomycin.

Different factors, including antimicrobial resistance, may diminish the effectiveness of antibiotic therapy, challenging the management of post-transplant urinary tract infection (UTI). The association of acidic urine pH with microbiological and clinical outcomes was evaluated after fosfomycin or ciprofloxacin therapy in 184 kidney transplant recipients (KTRs) with UTI episodes by Escherichia coli (N = 115) and Klebsiella pneumoniae (N = 69). Initial urine pH, antimicrobial therapy, and clinical and microbiological outcomes, and one- and six-month follow-up were assessed. Fosfomycin was prescribed in 88 (76.5%) E. coli and 46 (66.7%) K. pneumoniae UTI episodes in the total cohort. When the urine pH ≤ 6, fosfomycin was prescribed in 60 (52.2%) E. coli and 29 (42.0%) K. pneumoniae. Initial urine pH ≤ 6 in E. coli UTI was associated with symptomatic episodes (8/60 vs. 0/55, p = 0.04) at one-month follow-up, with a similar trend in those patients receiving fosfomycin (7/47 vs. 0/41, p = 0.09). Acidic urine pH was not associated with microbiological or clinical cure in K. pneumoniae UTI. At pH 5, the ciprofloxacin MIC90 increased from 8 to >8 mg/L in E. coli and from 4 to >8 mg/L in K. pneumoniae. At pH 5, the fosfomycin MIC90 decreased from 8 to 4 mg/L in E. coli and from 512 to 128 mg/L in K. pneumoniae. Acidic urine is not associated with the microbiological efficacy of fosfomycin and ciprofloxacin in KTRs with UTI, but it is associated with symptomatic UTI episodes at one-month follow-up in E. coli episodes.

Acinetobacter baumannii: assessing susceptibility patterns, management practices, and mortality predictors in a tertiary teaching hospital in Lebanon

BackgroundAcinetobacter baumannii is a major nosocomial pathogen capable of causing life-threatening infections. This bacterium is highly resistant to antibiotics and associated with high mortality rates. Therefore, this study aimed to evaluate A. baumannii's susceptibility patterns to antimicrobials, assess the appropriateness of the initiated antimicrobial therapy, determine the mortality rate, and identify predictors associated with mortality.MethodsA retrospective observational study was conducted among patients infected with A. baumannii at a university hospital in Lebanon through the revision of medical records. Kaplan–Meier survival analysis and log-rank tests were used to analyze time-to-mortality. Binary logistic regression was performed to identify predictors of mortality.ResultsThe records of 188 patients were screened, and 111 patients with A. baumannii infection were enrolled. Almost all isolates were resistant to carbapenem, and 43% of the isolates were extensively-drug resistant. Almost half of the patients received initial inappropriate antimicrobial therapy (n = 50, 45.1%). The 30-day mortality rate associated with A. baumannii infection was 71.2% (79/111). The time to mortality in patients who received inappropriate antimicrobial therapy (5.70 ± 1.07 days) was significantly shorter than in those who received appropriate antimicrobial therapy (12.43 ± 1.01 days, P < 0.01). Binary logistic regression revealed that inappropriate antimicrobial therapy (adjusted odds ratio [AOR] = 16.22, 95% CI 2.68–9.97, P = 0.002), mechanical ventilation (AOR = 14.72, 95% CI 3.27–6.61, P < 0.001), and thrombocytopenia (AOR = 8.82, 95% CI 1.12–9.75, P = 0.003) were more likely associated with mortality.ConclusionsA. baumannii exhibits an alarming mortality rate among infected patients. Thrombocytopenia, mechanical ventilation, and inappropriate antibiotic administration are associated with mortality in patients infected with A. baumannii. The prompt initiation of appropriate antimicrobial therapy, infection control measures, and effective stewardship program are crucial to reduce the incidence of A. baumannii and improve the treatment outcomes.

Initial antimicrobial therapy and case fatality in patients with community-acquired pneumonia

The health importance of community-acquired pneumonia is an unquestionable fact given its relationship with hospital and overall mortality. The objective of the investigation was to evaluate the relationship between selected antimicrobials used in the initial treatment (amoxicillin/sulbactam, cefuroxime, ceftriaxone and cefotaxime) and mortality from pneumonia. An observational study was carried out, with a descriptive design and a population of 1,809 patients with pneumonia hospitalized between 2012 and 2019; the necessary information was obtained from the clinical history. Statistical processing was performed using bivariate and multivariate analysis (logistic regression); the ratio of cross products (odds ratio) and its 95% confidence interval were used as a statistician. Among the results, the following stand out: significantly higher lethality values were found in those treated with cefotaxime (33%) than in those who received amoxicillin/sulbactam (24%, OR 1.6[1.0001;2.6]), as well as in those treated with ceftriaxone (30%) compared with those treated with amoxicillin/sulbactam (24%, OR 1.3[1.05;1.8]) and with cefuroxime (24%, OR 1.3[1.04;1.7]). A higher frequency of patients with extensive pneumonia, of patients in a critical state on admission, and of bedridden occurrence during hospitalization were identified in those treated with cefotaxime. In patients with “moderate pneumonia and high probability of unfavorable outcome”, treatment with ceftriaxone or cefotaxime was associated with death; as well as ceftriaxone treatment for all subjects. It is concluded that the initial treatment with amoxicillin/ sulbactam or cefuroxime was more favorable than the use of third generation cephalosporins. Also in the global analysis, the absence of differences in lethality between those treated with amoxicillin/sulbactam and with cefuroxime was recognized.

Diminished antimicrobial drug use in dogs with allergic dermatitis treated with oclacitinib.

Dogs with allergic dermatitis often suffer concurrent skin and ear infections. The objective of this study was to retrospectively quantify the number of systemic and topical antimicrobial transactions in dogs with allergic dermatitis, following administration of oclacitinib or a glucocorticoid, compared to dogs that did not receive a pruritus therapy when there is an initial diagnosis of pyoderma. A secondary objective was to demonstrate that dogs on oclacitinib use fewer antimicrobials and concomitant therapies over time and have improved quality of life. This was a retrospective case-control study using a large, centralized database to identify canine patients receiving pruritus therapy along with a concurrent diagnosis of pyoderma. For the second objective, 58 client-owned dogs diagnosed with allergic dermatitis were enrolled in a prospective owner and dog quality of life and treatment satisfaction (QoL&TS) study that also evaluated concomitant therapy use over time. In Part A, data consisted of anonymous transaction records from 1,134 hospitals across the United States, representing pyoderma visits between December 2018 and December 2019. Odds ratios comparing the relative odds of having additional antimicrobial agent transactions were calculated, given initial pruritus therapy compared to dogs that did not receive pruritus therapy. Parametric bootstrapping was used to calculate goodness-of-fit statistics. In part B, dogs entered the study on Day 0 and returned for examination on Days 14, 21, 30, and 60. Owner determination of QoL&TS was performed on Days 0, 1, 3, 14, 21, 30, and 60. On Days 0, 14, 21, and 60, a veterinarian assessed concomitant therapies and dermatitis severity scoring. Least Squares Means and Standard Errors for QoL&TS, and Dermatitis Vet VAS (Visual Analog Scale) Scores were calculated using a Linear Mixed Model Approach for Repeated Measures (α = 0.05). The percent reduction in therapies was also calculated. Dogs that received oclacitinib (n = 5,132) or a glucocorticoid (n = 7,024) had reduced odds (OR: 0.8091; p = 0.0002 and OR: 0.7095; p < 0.0001, respectively) of having a follow up antimicrobial drug transaction after initial antimicrobial therapy compared to dogs with no pruritus therapy at the initial visit (n = 12,997). In part B, oclacitinib demonstrated a statistically significant improvement in QoL&TS scores over time QoL (p < 0.05). Veterinarian assessment showed a 70% reduction in dermatitis severity over time (p < 0.05), supporting oclacitinib's anti-inflammatory effects. Oclacitinib therapy was also associated with an 83% reduction in concomitant treatments, including a 100% reduction in systemic antimicrobial therapy over eight weeks. Dogs receiving oclacitinib showed no increase in antimicrobial therapy transactions compared to glucocorticoid recipients at the initial pyoderma diagnosis. Having a pruritus therapy at the index pyoderma visit reduced the odds of subsequent antimicrobial transactions. In addition to reducing concomitant therapy usage, oclacitinib improved owner and pet QoL, suggesting a paradigm shift in treatment success that could reshape allergic pruritus therapy recommendations. The study provides empirical evidence of oclacitinib's reduction in antibacterial therapy, supporting its therapeutic value and antimicrobial stewardship.

Epidemiology, Associated Factors, and Outcomes of Intensive Care Unit–Acquired Infections Caused by Multidrug-Resistant Organism in Critically Ill Patients

Abstract Background Nosocomial infections are a major health problem in the intensive care unit (ICU). Limited data exist on the epidemiology of ICU-acquired multidrug-resistant (MDR) microorganism infection. The study aimed to define the clinical characteristics, risk factors, and outcomes associated with the occurrence of an ICU-acquired MDR infection. Methods This is a retrospective, observational, single-center, case-control study, including all patients admitted to the unit between January 2015 and December 2019. Results During the study period, 3507 patients were admitted in the ICU. The overall incidence of ICU nosocomial infection was 9.6%, whereas the incidence of MDR infection was 0.9%, remaining stable throughout the study period. Based on multivariate analysis, only the presence of neutropenia on admission, days of mechanical ventilation, days with a urinary catheter, and ICU length of stay were identified as clinical factors independently associated with MDR infections. The occurrence of these infections was associated with increased length of stay and need for invasive devices, although there were no differences in associated mortality between groups. There was a 46% rate of pathogen-directed antibiotic treatment in cases of MDR infection, although when empirical treatment is used, MDR patients were less likely to receive initial appropriate antimicrobial therapy (25% vs 7%; P &lt; 0.001). Conclusions Multidrug-resistant infections presented a nonnegligible incidence and are associated with the existence of immunosuppression before admission, as well as the need for mechanical ventilation, urinary catheter, and prolonged ICU stay. They represent an increase in patient morbidity, although they are not related to an increase in mortality.

Management of localized aggressive periodontitis: A case report

The aim of this case report is to describe the importance of early diagnosis and treatment to prevent the progression of localized aggressive periodontitis. A 16 years old systemically healthy female patient with a chief complaint of increased mobility and spacing in relation to mandibular anteriors was successfully treated with initial non-surgical periodontal therapy and antimicrobial therapy (as an adjunct therapy), followed by surgical intervention. Patient was followed-up for 6 months. Patient education to maintain adequate oral hygiene and good patient compliance along with periodontal treatment led to successful preservation of esthetics and function.

Assessment of risk factors associated with multidrug-resistant organism infections among patients admitted in a tertiary hospital - a retrospective study

BackgroundBacterial resistance has become a global health concern. To treat suspected multidrug resistant organisms (MDROs), physicians first use broad-spectrum antibiotics; however, this increases the chance of developing antimicrobial resistance. Thus, defining the risk factors for MDROs could aid in the selection of the ideal initial antimicrobial therapy and improve clinical outcomes. ObjectiveThis study aimed to identify the common risk factors for MDRO infection among patients admitted to King Fahad Hospital (KFH) and to analyze the comorbidity factors associated with MDRO infections. MethodsThis retrospective, observational, case-control study included adult patients ≥ 18 years old admitted to KFH between 1st of January to 31st of March 2021, with positive microbial culture. Pediatric patients, outpatients, or patients with only positive fungal cultures were excluded. Data were obtained from the KFH laboratory MDRO documenting database. ResultsTwo hundred and seventy patients were included in this study: 136 in the study group and 134 in the control group. Among patients, 167 (61.9 %) were males and 184 (68.1%) were 18 to 65 years old. The use of drugs such as cotrimoxazole, amikacin, and imipenem (OR = 4.331, C. I. of OR:1.728, 10.855, p = 0.002) were significantly associated with MDRO infections, whereas cefazolin was associated with a lower risk of MDRO infections (OR = 0.080, C.I. of OR:0.018, 0.347, p < 0.001). The intensive care unit showed higher odds of significant association with MDRO infections than those of the surgical unit (odds ratio [OR] = 8.717, 95% C.I. of OR: 3.040, 24.998, p < 0.001). Patients who previously consumed acid-suppressive medications showed higher odds of developing MDRO infections (OR = 5.333, C.I. of OR: 2.395, 11.877, p < 0.001). ConclusionThe most significant comorbidities were diabetes, hypertension, antibiotic use prior to hospitalization and the use of cotrimoxazole, amikacin and imipenem among other antibtiotics was mostly associated with MRDO infections. This study revealed an increasing trend of MDRO infections and a positive correlation with the incidence of strokes and mortality, which highlights the importance of understanding the risk factors for MDRO infections.

Wound Complication and Surgical Site Infection in Sarcoma Patients Undergoing Internal Hemipelvectomy

Abstract Background Hemipelvectomy is associated with a significant risk of wound complications, including infections, bleeding, and injuries to nearby neurovascular structures as well as the gastrointestinal and genitourinary tract. This study aimed to determine the patient characteristics and approach to treatment that could affect the occurrence of surgical site infection or wound complications in sarcoma patients who have undergone hemipelvectomy. Methods We conducted a retrospective analysis of 33 adult patients who underwent hemipelvectomy at a large tertiary academic cancer center from 2008 to 2016. We used χ 2 (exact Fisher) test to investigate the association between wound complication and categorical variables. We used a t test to evaluate the difference in numerical variables for outcomes. Results Among 33 patients, 12 patients (36.4%) experienced wound complications after hemipelvectomy. The average age of patients with wound complications was 63.3 years (57.1 ± 15.4 years), significantly higher than that of patients without wound complications (P = 0.004). Without adjustment, the use of computer navigation had a lower wound complication rate (P = 0.027). Patients with wound complications had longer hospital length of stay (14.8 vs 7.0 days, P = 0.016). Patient and surgical characteristics were not associated with surgical site infection. Five patients (15%) developed surgical site infection, and they had longer hospital stay (19.4 vs 8.1 days, P = 0.001). Conclusion Older patients undergoing hemipelvectomy are at an increased risk of developing wound complications with a prolonged hospital stay. Initial antimicrobial therapy for suspected surgical site infection should include broad-spectrum coverage to include skin and gastrointestinal flora.

Association of Appropriate Empirical Antimicrobial Therapy With In-Hospital Mortality in Patients With Bloodstream Infections in the US

Bloodstream infections (BSIs) are a major public health problem associated with high morbidity. Little evidence exists regarding the epidemiology of BSIs and the use of appropriate empirical antimicrobial therapy. To estimate the association between receipt of appropriate initial empirical antimicrobial therapy and in-hospital mortality. This retrospective cross-sectional study used data from the Premier Healthcare database from 2016 to 2020. The analysis included 32 100 adult patients (aged ≥18 years) with BSIs from 183 US hospitals who received at least 1 new systemic antimicrobial agent within 2 days after blood samples were collected during the hospitalization. Patients with polymicrobial infections were excluded from the analysis. Appropriate empirical therapy was defined as initiation of at least 1 new empirical antimicrobial agent to which the pathogen isolated from blood culture was susceptible either on the day of or the day after the blood sample was collected. Multilevel logistic regression models were used to estimate the association between receipt of appropriate initial empirical antimicrobial therapy and in-hospital mortality for patients infected with gram-negative rods (GNRs), gram-positive cocci (GPC), and Candida species. Among 32 100 patients who had BSIs and received new empirical antimicrobial agents, the mean (SD) age was 64 (16) years; 54.8% were male, 69.9% were non-Hispanic White, and in-hospital mortality was 14.3%. The most common pathogens were Escherichia coli (58.4%) and Staphylococcus aureus (31.8%). Among patients infected with S aureus, methicillin-resistant S aureus was isolated in 43.6%. The crude proportions of appropriate empirical therapy use were 94.4% for GNR, 97.0% for GPC, and 65.1% for Candida species. The proportions of appropriate therapy use for resistant organisms were 55.3% for carbapenem-resistant Enterobacterales species and 60.4% for vancomycin-resistant Enterococcus species. Compared with inappropriate empirical therapy, receipt of appropriate empirical antimicrobial therapy was associated with lower in-hospital risk of death for 3 pathogen groups (GNR: adjusted odds ratio [aOR], 0.52 [95% CI, 0.42-0.64]; GPC: aOR, 0.60 [95% CI, 0.47-0.78]; Candida species: aOR, 0.43 [95% CI, 0.21-0.87]). In this cross-sectional study of patients hospitalized with BSIs, receipt of appropriate initial empirical antimicrobial therapy was associated with lower in-hospital mortality. It is important for clinicians to carefully choose empirical antimicrobial agents to improve outcomes in patients with BSIs.

Can Gram staining be a guiding tool for optimizing initial antimicrobial agents in bacterial infections?

The emergence of multidrug-resistant organisms poses a significant threat to global public health, making the optimization of antimicrobial use crucial. Antimicrobial therapy is often initiated in emergency rooms (ERs) and intensive care units (ICUs), where patients are at high risk of infection. Prompt antimicrobial selection is essential in these facilities, and point-of-care testing can guide the appropriate initial antimicrobial therapy. Gram staining, a quick and inexpensive method, was previously used for point-of-care testing by physicians in the 1980s but was discontinued in 1988 in the United States. However, in Japan, the clinical practice of Gram stain-based antimicrobial therapy by physicians has continued in a limited number of hospitals. Several studies undertaken in Japan have shown that Gram staining carried out by trained physicians can reduce the overuse of broad-spectrum antimicrobial agents in ERs and ICUs without worsening patients' outcomes. Gram stain-based antimicrobial therapy reduced unnecessary use of carbapenems in the ER. Furthermore, Gram staining has been shown to significantly reduce the overuse of broad-spectrum antimicrobials without worsening clinical cure and mortality for patients with ventilator-associated pneumonia in the ICU. The classic technique of Gram staining has regained its usefulness through persistent clinical practice in Japan. It is hoped that Japanese researchers in this field will demonstrate to the world the efficacy of the classic technique of Gram staining in addressing this critical problem. Gram staining carried out by trained physicians could serve as a valuable means of optimizing antimicrobial treatment in ERs and ICUs.

ALCALIGENES FAECALIS, AN UNEXPECTED AGENT OF URINARY TRACT INFECTION IN A 14-YEARS-OLD BOY

Introduction: Alcaligenes faecalis is a rare cause of urinary tract infection (UTI) in humans, especially in pediatrics. It is a potentially emerging pathogen, usually opportunistic, and it is often difficult to treat due to its increased resistance to several antibiotics. Urinary tract infection due to Alcaligenes faecalis in pediatrics it is not yet describe in literature. Case report: We report the occurrence of Alcaligenes faecalis (spp faecalis) Urinary Tract Infection (UTI), presenting as acute cystitis, in a 14-years-old boy with previous history of non-obstructive bilateral renal lithiasis due to hyperuricosuria, pyelocaliceal duplicity in the right kidney and recurrent UTI. He was treated with empirical antibiotic with amoxicillin/clavulanate, with clinical improvement. A repeated urine culture was sterile after treatment. Discussion: We review literature in pediatrics, and we found out that this agent is a very uncommon organism of infection and difficult to treat due to its increased resistance to several antibiotics such as penicillin, cephalosporins, carbapenems, aminoglycosides, and quinolones. In pediatric literature, there is still few cases of infection described, due to Alcaligenes faecalis. Conclusions: Clinicians should continue to direct initial empiric antimicrobial therapy toward the more commonly encountered bacteria. If Alcaligenes faecalis is identified in culture, it can represent a true pathogen, and not merely a contaminant. Alcaligenes faecalis is an unexpected agent of UTI that clinicians should keep in mind.

680. Utility of Cefoxitin for the Treatment of ESBL-producing E. coli Urinary Tract Infections

Abstract Background Carbapenems are regarded as first-line agents for the treatment of ESBL-producing bacterial infections, even when in vitro activity to other beta lactams is demonstrated. However, overuse is associated with the selection of beta-lactamases that can hydrolyze carbapenems. Patients with isolated urinary tract infections due to ESBL–producing E. coli potentially have a lower burden of infection ("low inoculum"). These patients are frequently less ill and may benefit from non-carbapenem therapy. Cephamycins have in vitro activity against ESBL–producing Enterobacterales, and may be useful in the treatment of ESBL E. coli urinary tract infections as a carbapenem sparing agent. Methods Patients 18 years of age and older, hemodynamically stable with negative blood cultures and who demonstrated signs and symptoms of a urinary tract infection with a urine culture showing ESBL E. coli, were eligible to participate. Patients were started on initial antimicrobial therapy at the discretion of the admitting physician, and if the urine culture showed ESBL E. coli with an MIC of less than 8, the antimicrobial stewardship team requested to switch the patient to Cefoxitin 2 g intravenously every 6 hours, via extended infusion. The dose was renally adjusted as appropriate, and patients with beta-lactam allergies were excluded. Results 46 patients were evaluated between May 2017-April 2022. Patients received antibiotics for 2.6+1 day before the switch to Cefoxitin. The mean duration of therapy with Cefoxitin was 4.5+2.2 days. All 46 patients had resolution of fever and dysuria. Six patients were readmitted within 30 days, but none were due to a urinary tract infection. 30 patients had a repeat urinalysis at 48 hours, and all demonstrated reduction in pyuria. 39 patients had a repeat urine culture following completion of therapy, and 36 had converted to culture-negative status. Conclusion Cefoxitin is a useful agent for the treatment of ESBL E. coli urinary tract infections. The optimal dose appears to be 2 g intravenously every 6 hours, via extended infusion, in patients with normal creatinine clearance. Further larger studies, involving patients with pyelonephritis, are needed to validate these findings. Disclosures Ramesh V. Nathan, MD, Eli Lilly: Grant/Research Support|PPD: Grant/Research Support.

Risk Factors Associated With Antimicrobial Resistance and Adverse Short-Term Health Outcomes Among Adult and Adolescent Female Outpatients With Uncomplicated Urinary Tract Infection.

Increasing antimicrobial resistance makes treating uncomplicated urinary tract infections (uUTIs) difficult. We compared whether adverse short-term outcomes among US female patients were more common when initial antimicrobial therapy did not cover the causative uropathogen. This retrospective cohort study used data from female outpatients aged ≥12 years, with a positive urine culture and dispensing of an oral antibiotic ±1 day from index culture. Isolate susceptibility to the antimicrobial initially dispensed, patient age, and history of antimicrobial exposure, resistance, and all-cause hospitalization within 12 months of index culture were evaluated for associations with adverse outcomes during 28-day follow up. Outcomes assessed were new antimicrobial dispensing, all-cause hospitalization, and all-cause outpatient emergency department/clinic visits. Of 2366 uUTIs, 1908 (80.6%) were caused by isolates susceptible and 458 (19.4%) by isolates not susceptible (intermediate/resistant) to initial antimicrobial treatment. Within 28 days, patients with episodes caused by not susceptible isolates were 60% more likely to receive a new antimicrobial versus episodes with susceptible isolates (29.0% vs 18.1%; 95% confidence interval, 1.3-2.1; P < .0001). Other variables associated with new antibiotic dispenses within 28 days were older age, prior antimicrobial exposure, or prior nitrofurantoin-not-susceptible uropathogens (P < .05). Older age, prior antimicrobial-resistant urine isolates, and prior hospitalization were associated with all-cause hospitalization (P < .05). Prior fluoroquinolone-not-susceptible isolates or oral antibiotic dispensing within 12 months of index culture were associated with subsequent all-cause outpatient visits (P < .05). New antimicrobial dispensing within the 28-day follow-up period was associated with uUTIs where the uropathogen was not susceptible to initial antimicrobial treatment. Older age and prior antimicrobial exposure, resistance, and hospitalization also identified patients at risk of adverse outcomes.

Time to appropriate antimicrobial therapy serves an independent prognostic indicator in children with nosocomial Klebsiella pneumoniae bloodstream infection

We tend to investigate the connection between time to appropriate therapy (TTAT) and prognosis in pediatric patients with nosocomial Klebsiella pneumoniae (K. pneumoniae) bloodstream infection, and find the optimal cutoff point for the empirical administration of antimicrobials. This retrospective study was conducted in Children’s Hospital of Chongqing Medical University, and inpatients with nosocomial K. pneumoniae bloodstream infection were finally enrolled. We applied the Classification and Regression Tree (CART) analysis to find the TTAT cutoff point and the Logistic Regression analysis to evaluate prognostic indicators. The incidence of septic shock and mortality was 17.91% (12/67) and 13.43% (9/67), respectively. The CART-derived TTAT cutoff point was 10.7 h. The multivariate logistic regression analysis indicated delayed therapy (TTAT ≥ 10.7 h), pediatric risk of mortality (PRISM) III scores ≥ 10, time to positivity (TTP) ≤ 13 h, and requiring for invasive mechanical ventilation were independently associated with the incidence of septic shock (Odds ratio [OR] 9.87, 95% Confidence interval [CI] 1.46–66.59, P = 0.019; OR 9.69, 95% CI 1.15–81.39, P = 0.036; OR 8.28, 95% CI 1.37–50.10, P = 0.021; OR 6.52, 95% CI 1.08–39.51, P = 0.042; respectively) and in-hospital mortality (OR 22.19, 95% CI 1.25–393.94, P = 0.035; OR 40.06, 95% CI 2.32–691.35, P = 0.011; OR 22.60, 95% CI 1.78–287.27, P = 0.016; OR 12.21, 95% CI 1.06–140.67, P = 0.045; respectively).Conclusions TTAT is an independent predictor of poor outcomes in children with nosocomial K. pneumoniae bloodstream infection. Initial appropriate antimicrobial therapy should be administrated timely and within 10.7 h from the onset of bloodstream infection is recommended.

Intensivists' perceptions and attitudes towards infectious diseases management in the ICU: An international survey.

Exploring infectious diseases (ID) practice in Intensive Care Unit (ICU) to identify gaps and opportunities. Online international survey (PRACT-INF-ICU) endorsed by the ESICM and open from July 30, 2019 to October 19, 2019. International study conducted in 78 countries. Physicians working in ICU. None. Practice variations were assessed according to respondents' countries income class, training, and years of practice. Univariate and multivariate ordinal logistic regression were used to estimate associations between respondents' characteristics and their perceptions regarding adequacy of training. 466 intensivists with a median practice of 10 years (interquartile range, 5-19) completed the survey. A third reported no antimicrobial stewardship program and 40% had no regular microbiological rounds in their ICUs. Intensivists were mostly the decision makers for the initial antimicrobial therapy which in 70% of cases were based on guidelines or protocols. Non-ICU expertise were sought more frequently on reviewing (48/72h, culture adjustment and discontinuation in 32%, 39% and 21% respectively) rather than antimicrobial therapy initiation (16%). Only 42% described ID training as adequate. Multivariate ordinal logistic regression showed that low- to middle-income countries (OR: 0.41, 95% CI: 0.28-0.61), ICU practice ≤10 years (OR: 0.55, 95% CI: 0.39-0.79), and dual training with anaesthesia (OR: 0.52, 95% CI: 0.34-0.79) or medicine (OR: 0.49, 95% CI: 0.32-0.76) were associated with less training satisfaction. ID practice is heterogeneous across ICUs while antimicrobial stewardship program is not universally implemented. From intensivists' perspective, ID training and knowledge need improvement.

Intensivists’ perceptions and attitudes towards infectious diseases management in the ICU: An international survey

ObjectiveExploring infectious diseases (ID) practice in Intensive Care Unit (ICU) to identify gaps and opportunities. DesignOnline international survey (PRACT-INF-ICU) endorsed by the ESICM and open from July 30, 2019 to October 19, 2019. SettingInternational study conducted in 78 countries. ParticipantsPhysicians working in ICU. InterventionsNone. Main variables of interestPractice variations were assessed according to respondents’ countries income class, training, and years of practice. Univariate and multivariate ordinal logistic regression were used to estimate associations between respondents’ characteristics and their perceptions regarding adequacy of training. Results466 intensivists with a median practice of 10 years (interquartile range, 5–19) completed the survey. A third reported no antimicrobial stewardship program and 40% had no regular microbiological rounds in their ICUs. Intensivists were mostly the decision makers for the initial antimicrobial therapy which in 70% of cases were based on guidelines or protocols. Non-ICU expertise were sought more frequently on reviewing (48/72h, culture adjustment and discontinuation in 32%, 39% and 21% respectively) rather than antimicrobial therapy initiation (16%). Only 42% described ID training as adequate. Multivariate ordinal logistic regression showed that low- to middle-income countries (OR: 0.41, 95% CI: 0.28–0.61), ICU practice ≤10 years (OR: 0.55, 95% CI: 0.39–0.79), and dual training with anaesthesia (OR: 0.52, 95% CI: 0.34–0.79) or medicine (OR: 0.49, 95% CI: 0.32–0.76) were associated with less training satisfaction. ConclusionID practice is heterogeneous across ICUs while antimicrobial stewardship program is not universally implemented. From intensivists’ perspective, ID training and knowledge need improvement.

#67 Treatment of Campylobacter upsaliensis and Helicobacter canis in twin brothers with XLA

Abstract Background X-linked agammaglobulinemia (XLA) is a primary immunodeficiency associated with mutations in the B cell tyrosine kinase gene leading to failure in B cell maturation, resulting in antibody deficiency and increased susceptibility to infections. Patients with XLA are at risk of severe disease with infections with Campylobacter and closely related Helicobacter species and warrant treatment with close follow up given risk of recurrence. Method We present follow up of two 5-year-old fraternal twins with XLA who were diagnosed with C. upsaliensis and H. canis respectively via microbial cell-free DNA (mcfDNA) and underwent successful treatment with multi-drug antimicrobial therapy with 12 months of follow-up. Results Patient #1 was diagnosed with XLA at 11 months of age. At 3 years of age, he presented with fever and diarrhea, with stool cultures that grew C. jejuni. Despite treatment with azithromycin, his symptoms persisted and repeat stool cultures grew C. upsaliensis. Testing via mcfDNA confirmed C. upsaliensis. Patient #2 was diagnosed with XLA at 12 months of age. He developed fever, erythema nodosum (EN) like lesions and arthritis at 3.5 years old. Given his twin’s diagnosis of Campylobacter sp. enteritis, he was given a presumptive diagnosis of Campylobacter reactive arthritis and EN. Despite treatment with Naprosyn and 14 days of azithromycin, his symptoms persisted and stool PCR was positive for Campylobacter sp. mcfDNA testing confirmed C. upsaliensis and H.canis. Given failure of initial antimicrobial therapy, both boys were treated with a 4-week course of IV ertapenem, and oral ciprofloxacin and amoxicillin, and both developed neutropenia and concern for drug toxicity. Therapy was transitioned to triple drug therapy with oral doxycycline, ciprofloxacin and amoxicillin. Doxycycline was discontinued after 3 weeks due to patients’ young age. Ciprofloxacin and amoxicillin were continued for 12 months. Both boys had complete resolution of symptoms after 12 months of therapy and remain without recurrence 10 weeks after discontinuation of antimicrobial therapy. Conclusion Physicians should be aware of the treatment challenges of chronic Campylobacter and Helicobacter infection in boys with XLA and other immunocompromised hosts. Successful treatment may require prolonged multi-drug antimicrobial therapy, with monitoring for drug toxicities.

A multifaceted educational intervention improved anti-infectious measures but had no effect on mortality in patients with severe sepsis

Sepsis is a major reason for preventable hospital deaths. A cluster-randomized controlled trial on an educational intervention did not show improvements of sepsis management or outcome. We now aimed to test an improved implementation strategy in a second intervention phase in which new intervention hospitals (former controls) received a multifaceted educational intervention, while controls (former intervention hospitals) only received feedback of quality indicators. Changes in outcomes from the first to the second intervention phase were compared between groups using hierarchical generalized linear models controlling for possible confounders. During the two phases, 19 control hospitals included 4050 patients with sepsis and 21 intervention hospitals included 2526 patients. 28-day mortality did not show significant changes between study phases in both groups. The proportion of patients receiving antimicrobial therapy within one hour increased in intervention hospitals, but not in control hospitals. Taking at least two sets of blood cultures increased significantly in both groups. During phase 2, intervention hospitals showed higher proportion of adequate initial antimicrobial therapy and de-escalation within 5 days. A survey among involved clinicians indicated lacking resources for quality improvement. Therefore, quality improvement programs should include all elements of sepsis guidelines and provide hospitals with sufficient resources for quality improvement.Trial registration: ClinicalTrials.gov, NCT01187134. Registered 23 August 2010, https://www.clinicaltrials.gov/ct2/show/study/NCT01187134.