Inappropriate Initial Antibiotic Research Articles

Impact of multidrug resistance on outcomes in hematologic cancer patients with bacterial bloodstream infections

Despite the improved outcomes in patients with hematological malignancies, infections caused by multidrug-resistant organisms (MDROs) pose a new threat to these patients. We retrospectively reviewed the patients with hematological cancer and bacterial bloodstream infections (BSIs) at a tertiary hospital between 2003 and 2022 to assess the impact of MDROs on outcomes. Among 328 BSIs, 81 (24.7%) were caused by MDROs. MDRO rates increased from 10.3% (2003–2007) to 39.7% (2018–2022) (P < 0.001). The 30-day mortality rate was 25.0%, which was significantly higher in MDRO-infected patients than in non-MDRO-infected patients (48.1 vs. 17.4%; P < 0.001). The observed trend was more pronounced in patients with newly diagnosed diseases and relapsed/refractory disease but less prominent in patients in complete remission. Among MDROs, carbapenem-resistant Gram-negative bacteria exhibited the highest mortality, followed by vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and extended-spectrum β-lactamase-producing Enterobacteriaceae. Multivariate analysis identified independent risk factors for 30-day mortality as age ≥ 65 years, newly diagnosed disease, relapsed/refractory disease, MDROs, polymicrobial infection, CRP ≥ 20 mg/L, and inappropriate initial antibiotic therapy. In conclusion, MDROs contribute to adverse outcomes in patients with hematological cancer and bacterial BSIs, with effects varying based on the underlying disease status and causative pathogens. Appropriate initial antibiotic therapy may improve patient outcomes.

Case Report: Severe Community-Acquired Pneumonia in Réunion Island due to Acinetobacter baumannii.

Acinetobacter baumannii (Ab) is a well-known nosocomial pathogen that has emerged as a cause of community-acquired pneumonia (CAP) in tropical regions. Few global epidemiological studies of CAP-Ab have been published to date, and no data are available on this disease in France. We conducted a retrospective chart review of severe cases of CAP-Ab admitted to intensive care units in Réunion University Hospital between October 2014 and October 2022. Eight severe CAP-Ab cases were reviewed. Median patient age was 56.5 years. Sex ratio (male-to-female) was 3:1. Six cases (75.0%) occurred during the rainy season. Chronic alcohol use and smoking were found in 75.0% and 87.5% of cases, respectively. All patients presented in septic shock and with severe acute respiratory distress syndrome. Seven patients (87.5%) presented in cardiogenic shock, and renal replacement therapy was required for six patients (75.0%). Five cases (62.5%) presented with bacteremic pneumonia. The mortality rate was 62.5%. The median time from hospital admission to death was 3 days. All patients received inappropriate initial antibiotic therapy. Acinetobacter baumannii isolates were all susceptible to ceftazidime, cefepime, piperacillin-tazobactam, ciprofloxacin, gentamicin, and imipenem. Six isolates (75%) were also susceptible to ticarcillin, piperacillin, and cotrimoxazole. Severe CAP-Ab has a fulminant course and high mortality. A typical case is a middle-aged man with smoking and chronic alcohol use living in a tropical region and developing severe CAP during the rainy season. This clinical presentation should prompt administration of antibiotic therapy targeting Ab.

High mortality associated with inappropriate initial antibiotic therapy in hematological malignancies with Klebsiella pneumoniae bloodstream infections

Bloodstream infections caused by multidrug-resistant organisms such as Klebsiella pneumoniae are a significant challenge in managing hematological malignancies. This study aims to characterize the epidemiology of Klebsiella pneumoniae bloodstream infections specifically in patients with hematological malignancies, delineate the patterns of initial antibiotic therapy, assess the prevalence of resistant strains, identify risk factors for these resistant strains, and evaluate factors influencing patient outcomes. A retrospective analysis was conducted at a single center from January 2017 to December 2020, focusing on 182 patients with hematological malignancies who developed Klebsiella pneumoniae bloodstream infections. We compared the 30-day mortality rates between patients receiving appropriate and inappropriate antibiotic treatments, including the effectiveness of both single-drug and combination therapies. Kaplan–Meier survival analysis and multivariate logistic and Cox regression were used to identify factors influencing mortality risk. The 30-day all-cause mortality rate was 30.2% for all patients. The 30-day all-cause mortality rates were 77.2% and 8.8% in patients who received inappropriate initial treatment and appropriate initial treatment (p < 0.001). Inappropriate initial treatment significantly influenced mortality and was a key predictor of 30-day mortality, along with septic shock and previous intensive care unit (ICU) stays. Patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections exhibited more severe clinical symptoms compared to the CSKP group. The study demonstrates a significant association between empirical carbapenem administration and the escalating prevalence of CRKP and multidrug-resistant K. pneumoniae (MDR-KP) infections. Furthermore, the study identified inappropriate initial antibiotic therapy, septic shock, and ICU admission as independent risk factors for 30-day mortality.

Risk factors for cefmetazole-non-susceptible bacteremia in acute cholangitis

IntroductionCefmetazole (CMZ), an antibiotic with limited international distribution, is recommended by the Tokyo Guidelines 2018 (TG18) for non-severe cases of acute cholangitis (AC). However, the risk factors for CMZ-non-susceptible (CMZ-NS) bacteremia in AC remain unclear. Here, we aimed to investigate the risk factors for CMZ-NS bacteremia and evaluate mortality in patients with AC. MethodsThis single-center, retrospective, observational study included all patients diagnosed with definite bacteremic AC, based on TG18, from April 2019 to March 2023. Risk factors for CMZ-NS bacteremia were analyzed by univariate, and age- and sex-adjusted, logistic regression analyses. Mortality was compared by cause of obstruction, CMZ-susceptible/CMZ-NS bacteremia, and initial treatment. ResultsIn total, 165 patients were enrolled. CMZ-NS bacteremia was diagnosed in 46 (27.9 %) patients. Histories of diabetes mellitus, hepato-biliary-pancreatic cancer, malignant biliary obstruction, and endoscopic sphincterotomy were identified as significant factors associated with the risk of CMZ-NS bacteremia.Thirteen patients died within 30 days of hospital admission. The mortality of patients with AC and malignant biliary obstruction was statistically higher than that of patients with bile duct stones. No patients with AC and bile duct stones died in the group with CMZ-NS bacteremia and inappropriate initial antibiotics. ConclusionsIn AC, a history of diabetes mellitus, hepato-biliary-pancreatic cancer, malignant biliary obstruction, and endoscopic sphincterotomy are associated with an increased risk of CMZ-NS bacteremia. Therefore, the choice of empiric therapy for AC should be based on the etiology and patient background, rather than on the severity.

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.

Determinants of Mortality for Ventilated Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia.

To determine if vHAP is an independent predictor of mortality among patients with nosocomial pneumonia. Single-center retrospective cohort study conducted at Barnes-Jewish Hospital, St. Louis, MO, between 2016 and 2019. Adult patients with a pneumonia discharge diagnosis were screened and patients diagnosed with vHAP and VAP were included. All patient data was extracted from the electronic health record. The primary outcome was 30-day all-cause mortality (ACM). One thousand one-hundred twenty unique patient admissions were included (410 vHAP, 710 VAP). Thirty-day ACM was greater for patients with vHAP compared with VAP (37.1% vs 28.5%; p = 0.003). Logistic regression analysis identified vHAP (adjusted odds ratio [AOR], 1.77; 95% CI, 1.51-2.07), vasopressor use (AOR, 2.34; 95% CI, 1.94-2.82), Charlson Comorbidity Index (1-point increments) (AOR, 1.21; 95% CI, 1.18-1.24), total antibiotic treatment days (1-d increments) (AOR, 1.13; 95% CI, 1.11-1.14), and Acute Physiology and Chronic Health Evaluation II score (1-point increments) (AOR, 1.04; 95% CI, 1.03-1.06) as independent predictors of 30-day ACM. The most common bacterial pathogens identified as causes of vHAP and VAP were Staphylococcus aureus, Enterobacterales species, and Pseudomonas aeruginosa. In this single-center cohort study with low rates of initial inappropriate antibiotic therapy, vHAP had greater 30-day ACM compared with VAP after adjusting for potential confounding variables including disease severity and comorbidities. This finding suggests that clinical trials enrolling patients with vHAP need to account for this outcome difference in their trial design and data interpretation.

The Clash of the Titans: COVID-19, Carbapenem-Resistant Enterobacterales, and First mcr-1-Mediated Colistin Resistance in Humans in Romania.

(1) Background: Antibiotic resistance and coronavirus disease-19 (COVID-19) represent a dual challenge in daily clinical practice, inducing a high burden on public health systems. Hence, we aimed to dynamically evaluate the impact of COVID-19 on patients with carbapenem-resistant Enterobacterales (CRE) urinary tract infections (UTIs), as well as the antibiotic resistance trends after the onset of the pandemic. (2) Methods: We conducted a prospective study including patients with CRE UTIs who were enrolled both pre- and during the pandemic from 2019 to 2022. We further performed a standardized and comparative clinical, paraclinical, and microbiological assessment between patients with and without COVID-19. (3) Results: A total of 87 patients with CRE UTIs were included in this study (46 pre-pandemic and 41 during the pandemic, of which 21 had associated Severe Acute Respiratory Syndrome Coronavirus-2 infection). Klebsiella pneumoniae was the main etiological agent of the UTIs, with the majority of strains (82.7%) being carbapenemase producers (mainly OXA-48 producers), while five of the 34 colistin-resistant isolates were harboring the mobile colistin resistance-1 (mcr-1) gene. COVID-19 patients presented a significantly worse outcome with higher rates of intensive care unit (ICU) admissions (66.7% for COVID patients vs. 18.2% for non-COVID patients, p < 0.001), while the fatality rates were also considerably higher among patients with concomitant viral infection (33.3% vs. 12.1%, p < 0.001). Besides COVID-19, additional risk factors associated with increased mortality were urinary catheterization, sepsis with K. pneumoniae, impaired liver and kidney function, and an inappropriate initial empiric antibiotic therapy. (4) Conclusions: COVID-19 showed a pronounced negative impact on patients with CRE UTIs, with significantly longer hospitalizations and higher ICU admissions and mortality rates.

A Large Multicenter Prospective Study of Community-Onset Healthcare Associated Bacteremic Urinary Tract Infections in the Era of Multidrug Resistance: Even Worse than Hospital Acquired Infections?

IntroductionHealthcare-associated (HCA) infections represent a growing public health problem. The aim of this study was to compare community-onset healthcare associated (CO-HCA) bacteremic urinary tract infections (BUTI) and hospital-acquired (HA)-BUTI with special focus on multidrug resistances (MDR) and outcomes.MethodsITUBRAS-project is a prospective multicenter cohort study of patients with HCA-BUTI. All consecutive hospitalized adult patients with CO-HCA-BUTI or HA-BUTI episode were included in the study. Exclusion criteria were: patients < 18 years old, non-hospitalized patients, bacteremia from another source or primary bacteremia, non-healthcare-related infections and infections caused by unusual pathogens of the urinary tract. The main outcome variable was 30-day all-cause mortality with day 1 as the first day of positive blood culture. Logistic regression was used to analyze factors associated with clinical cure at hospital discharge and with receiving inappropriate initial antibiotic treatment. Cox regression was used to evaluate 30-day all-cause mortality.ResultsFour hundred forty-three episodes were included, 223 CO-HCA-BUTI. Patients with CO-HCA-BUTI were older (p < 0.001) and had more underlying diseases (p = 0.029) than those with HA-BUTI. The severity of the acute illness (Pitt score) was also higher in CO-HCA-BUTI (p = 0.026). Overall, a very high rate of MDR profiles (271/443, 61.2%) was observed, with no statistical differences between groups. In multivariable analysis, inadequate empirical treatment was associated with MDR profile (aOR 3.35; 95% CI 1.77–6.35), Pseudomonas aeruginosa (aOR 2.86; 95% CI 1.27–6.44) and Charlson index (aOR 1.11; 95% CI 1.01–1.23). Mortality was not associated with the site of acquisition of the infection or the presence of MDR profile. However, in the logistic regression analyses patients with CO-HCA-BUTI (aOR 0.61; 95% CI 0.40–0.93) were less likely to present clinical cure.ConclusionThe rate of MDR infections was worryingly high in our study. No differences in MDR rates were found between CO-HCA-BUTI and HA-BUTI, in the probability of receiving inappropriate empirical treatment or in 30-day mortality. However, CO-HCA-BUTIs were associated with worse clinical cure.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00537-0.

Antibiotic susceptibility of bacterial strains and bacteriological profile from patients with lower respiratory tract infections in a teaching hospital

Lower respiratory tract infections (LRTI) are one of the commonest health problems demanding frequent consultation and hospitalization. Unnecessary and inappropriate initial antibiotic therapy is a potentially modifiable factor that is associated with increased mortality in patients with serious infections. To study bacterial profile and susceptibility pattern of lower respiratory tract infections in a teaching hospital.Prospective study done in the department of Microbiology at Prathima Institute of Medical Sciences, Nagunuru, Karimnagar, Telangana., Tover a period of 18 months ie from January 2019 to July 2020. A total of 120 samples from respiratory tract were studied for bacterial isolates and antibiotic susceptibility. A total of 120 cases were studied. The male to female ratio was 2:1. Among the bacterial isolates, 76.6% were Gram negative bacilli and 23.3% were gram positive cocci. Among Gram negative bacteria, the predominant bacterial isolate was Klebisella. pneumoniae (45.8%) followed by Pseudomonas. aeruginosa (28.3%.)Present study, was based on the pattern of resistance to commonly used antibiotics by organisms causing lower respiratory tract infections (LRTIs) in our institute. This may help us to study the more susceptible group of drugs in our institute which would help prepare an antibiogram and develop a policy for rational antibiotic prescription.

Multidrug-Resistant Healthcare-Associated Infections in Neonates with Severe Respiratory Failure and the Impacts of Inappropriate Initial Antibiotic Therap.

Background: Multidrug-resistant (MDR) pathogens have emerged as an important issue in neonatal intensive care units (NICUs), especially in critically ill neonates with severe respiratory failure. We aimed to investigate neonatal healthcare-associated infections (HAIs) caused by MDR pathogens and the impacts of inappropriate initial antibiotic therapy on the outcomes. Methods: We retrospectively analyzed all cases of HAIs in neonates with severe respiratory failure in a tertiary-level NICU in Taiwan between January 2014 and May 2020. All clinical features, microbiology, therapeutic interventions, and outcomes were compared between the MDR-HAI and non-MDR HAI groups. Multivariate regression analyses were used to investigate independent risk factors for sepsis-attributable mortality. Results: A total of 275 critically ill neonates with severe respiratory failure who had HAIs were enrolled. Ninety-five cases (34.5%) were caused by MDR pathogens, and 141 (51.3%) cases had positive bacterial cultures from multiple sterile sites. In this cohort, the MDR-HAI group was more likely to receive inappropriate initial antibiotic therapy (51.0% versus 4.7%, respectively; p < 0.001) and exhibit delayed control of the infectious focus (52.6% versus 37.8%, respectively; p = 0.021) compared with the non-MDR HAI group. The sepsis-attributable and final in-hospital rates were 21.8% and 37.1%, respectively, and they were comparable between the MDR-HAI and non-MDR HAI groups. Empirically broad-spectrum antibiotics were prescribed in 76.7% of cases, and inappropriate initial antibiotic treatment was not significantly associated with worse outcomes. Independent risk factors for sepsis-attributable mortality in neonates with severe respiratory failure included the presence of septic shock (OR: 3.61; 95% CI: 1.54–8.46; p = 0.003), higher illness severity (OR: 1.33; 95% CI: 1.04–1.72; p = 0.026), and neonates with bronchopulmonary dysplasia (OR: 2.99; 95% CI: 1.47–6.09; p = 0.003). Conclusions: MDR pathogens accounted for 34.5% of all neonatal HAIs in the NICU, but neither MDR pathogens nor inappropriate initial antibiotics were associated with final adverse outcomes. Because the overuse of broad-spectrum antibiotics has emerged as an important issue in critically ill neonates, the implementation of antimicrobial stewardship to promote the appropriate use of antimicrobials is urgently needed.

1630. What is Treatment Time Zero Among Hospitalized Patients with Bacteremia?

BackgroundCommon operational definitions of antibiotic exposures in infectious diseases research do not accurately reflect actual treatment, as daily changes in clinical presentation (i.e. improvement, worsening) and clinical information (i.e. causative organism, susceptibilities) lead to frequent changes in treatment, both within empiric and definitive treatment periods. Common definitions create periods of ‘ignored’ exposures, and we’ve previously shown that antibiotic treatments during ‘ignored’ periods vary widely. Therefore, we assessed the distribution of important time points for antibiotic treatments for Staphylococcus aureus bacteremia.MethodsOur retrospective cohort study included hospital admissions in the national Veterans Affairs (VA) Healthcare System with S. aureus positive blood cultures from 2010 to 2018. Admissions with inappropriate initial antibiotic therapy for S. aureus were excluded. We implemented daily exposure mapping to identify antibiotic exposures and changes in treatment on each day of the admission until discharge, or 30 days post-admission for longer stays, and in relation to the culture final report date.ResultsWe identified 21,947 admissions meeting our inclusion criteria. Antibiotic initiation most often occurred on the culture collection date (68.7%) or the day after (22.6%). Median time to the culture final report date from the culture collection date was 4 days (interquartile range [IQR] 3 to 5). Among those with changes in therapy (n=19,392, 88.4%), median time to first change in therapy was 2 days prior to the culture final report date (IQR -3 to -1). The first change in therapy occurred before the culture final report date for 76.3% of admissions and on the culture final report date for 11.9% of admissions. Further changes were common on the culture final report date (49.5%) and the day after the final report date (45.3%).ConclusionChanges in antibiotic therapy are common prior to finalization of culture reports. While initial culture results and provider knowledge of these initial results are not date/time-stamped, initial change within a reasonable period from culture collection appears to be more accurate in defining empiric and definitive treatment periods than commonly used operational definitions.Disclosures Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi (Research Grant or Support)

Gram-negative bacilli bacteremia: a 7 year retrospective study in a referral Brazilian tertiary-care teaching hospital.

Introduction. Bloodstream infection is one of the most frequent and challenging hospital-acquired infections and it is associated with high morbidity, mortality and additional use of healthcare resources.Hypothesis/Gap Statement: Bloodstream infections have consequences for the patient, such as the evolution to mortality and inappropriate empirical antibiotic prescription, especially when caused by multidrug-resistant Gram-negative bacilli.Objective. To assess the impact of bloodstream infection and the status of multidrug resistance (MDR) in the evolution of patients who received inappropriate initial antibiotic therapy.Methods. A retrospective surveillance was conducted on nosocomial bloodstream infections caused by Gram-negative bacilli (GNB) from January 2012 to December 2018 in an adult intensive care unit of a Brazilian tertiary teaching hospital.Results. We identified 270 patients with GNB nosocomial bacteremia. Non-survivors were older (with an average age of 58.8 years vs 46.9 years, P=<0.0001), presented more severe illnesses, were immunosuppressed (73.7 vs 37.6%, P=<0.0001), were more likely to have septic shock (55.8 vs 22.4%, P=<0.0001) and had an increased usage of mechanical ventilators (98.6 vs 89.6%, P=0.0013) than survivors. In a logistic regression model, inappropriate empirical antibiotic therapy was not an independent predictor of mortality, different from mechanical ventilator (P=<0.0001; OR=28.0; 95% CI=6.3-123.6), septic shock (P=0.0051; OR=2.5; 95% CI=1.3-4.9) and immunosuppression (P=0.0066; OR=2.6; 95% CI=1.3-5.2). In contrast, in a separate model, MDR was strongly associated with the prescription of inappropriate initial antibiotic therapy (P=0.0030; OR=5.3; 95% CI=1.7-16.1). The main isolated pathogens were Acinetobacter baumannii (23.6 %) and Klebsiella pneumoniae (18.7 %). The frequency of MDR organisms was high (63.7 %), especially among non-fermenting bacilli (60.9 %), highlighting A. baumannii (81.6 %) and Pseudomonas aeruginosa (41.8 %).Conclusion. Illness severity (septic shock and immunosuppression) and mechanical ventilation were identified as predictors of mortality. Additionally, MDR was a major determinant of inappropriate antibiotic empirical therapy, but not associated with mortality, and both characteristics were not statistically associated with death.

Impacts of Multidrug-Resistant Pathogens and Inappropriate Initial Antibiotic Therapy on the Outcomes of Neonates with Ventilator-Associated Pneumonia.

: BackgroundIt is unknown whether neonatal ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) pathogens and inappropriate initial antibiotic treatment is associated with poor outcomes after adjusting for confounders. Methods: We prospectively observed all neonates with a definite diagnosis of VAP from a tertiary level neonatal intensive care unit (NICU) in Taiwan between October 2017 and March 2020. All clinical features, therapeutic interventions, and outcomes were compared between the MDR–VAP and non-MDR–VAP groups. Multivariate regression analyses were used to investigate independent risk factors for treatment failure. Results: Of 720 neonates who were intubated for more than 2 days, 184 had a total of 245 VAP episodes. The incidence rate of neonatal VAP was 10.1 episodes/per 1000 ventilator days. Ninety-six cases (39.2%) were caused by MDR pathogens. Neonates with MDR–VAP were more likely to receive inadequate initial antibiotic therapy (51.0% versus 4.7%; p < 0.001) and had delayed resolution of clinical symptoms (38.5% versus 25.5%; p = 0.034), although final treatment outcomes were comparable with the non-MDR–VAP group. Inappropriate initial antibiotic treatment was not significantly associated with worse outcomes. The VAP-attributable mortality rate and overall mortality rate of this cohort were 3.7% and 12.0%, respectively. Independent risk factors for treatment failure included presence of concurrent bacteremia (OR 4.83; 95% CI 2.03–11.51; p < 0.001), septic shock (OR 3.06; 95% CI 1.07–8.72; p = 0.037), neonates on high-frequency oscillatory ventilator (OR 4.10; 95% CI 1.70–9.88; p = 0.002), and underlying neurological sequelae (OR 3.35; 95% CI 1.47–7.67; p = 0.004). Conclusions: MDR–VAP accounted for 39.2% of all neonatal VAP in the neonatal intensive care unit (NICU), but neither inappropriate initial antibiotics nor MDR pathogens were associated with treatment failure. Neonatal VAP with concurrent bacteremia, septic shock, and underlying neurological sequelae were independently associated with final worse outcomes.

Pseudomonas infections among hospitalized adults in Latin America: a systematic review and meta-analysis

BackgroundTreatment of resistant Pseudomonas aeruginosa infection continues to be a challenge in Latin American countries (LATAM). We synthesize the literature on the use of appropriate initial antibiotic therapy (AIAT) and inappropriate initial antibiotic therapy (IIAT) in P. aeruginosa infections, and the literature on risk factors for acquisition of resistant P. aeruginosa among hospitalized adult patients in LATAM.MethodsMEDLINE, EMBASE, Cochrane, and LILAC were searched between 2000 and August 2019. s and full-text articles were screened in duplicate. Random effects meta-analysis was conducted when studies were sufficiently similar.ResultsThe screening of 165 citations identified through literature search yielded 98 full-text articles that were retrieved and assessed for eligibility, and 19 articles conducted in Brazil (14 articles), Colombia (4 articles), and Cuba (1 article) met the inclusion criteria. Of 19 eligible articles, six articles (840 subjects) examined AIAT compared to IIAT in P. aeruginosa infections; 17 articles (3203 total subjects) examined risk factors for acquisition of resistant P. aeruginosa; and four articles evaluated both. Four of 19 articles were rated low risk of bias and the remaining were deemed unclear or high risk of bias. In meta-analysis, AIAT was associated with lower mortality for P. aeruginosa infections (unadjusted summary OR 0.48, 95% CI 0.28–0.81; I2 = 59%), compared to IIAT and the association with mortality persisted in subgroup meta-analysis by low risk of bias (3 articles; unadjusted summary OR 0.46, 95% CI 0.28–0.81; I2 = 0%). No meta-analysis was performed for studies evaluating risk factors for acquisition of resistant P. aeruginosa as they were not sufficiently similar. Significant risk factors for acquisition of resistant P. aeruginosa included: prior use of antibiotics (11 articles), stay in the intensive care unit (ICU) (3 articles), and comorbidity score (3 articles). Outcomes were graded to be of low strength of evidence owing to unclear or high risk of bias and imprecise estimates.ConclusionOur study highlights the association of AIAT with lower mortality and prior use of antibiotics significantly predicts acquiring resistant P. aeruginosa infections. This review reinforces the need for rigorous and structured antimicrobial stewardship programs in the LATAM region.

Successful treatment of direct hemoperfusion with polymyxin B-immobilized fiber for septic shock and severe acute kidney injury due to ceftriaxone-resistant Escherichia coli: a case report with literature review

BackgroundSeptic shock is a life-threatening condition and one of the most common causes of acute kidney injury. Polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) is used to reduce endotoxin levels in blood. Here, we report a rare but important case of sepsis-induced acute kidney injury and septic shock, which was successfully treated with PMX-DHP in spite of inappropriate initial antibiotic therapy.Case presentationAn 84-year-old man was hospitalized for septic shock and acute kidney injury. Although he was treated with ceftriaxone, he did not recover from hypotension and had reduced urine output. After initiating PMX-DHP on days 3 and 4, his blood pressure was immediately elevated and his white blood cell count and C-reactive protein levels improved. Because ceftriaxone-resistant Escherichia coli was identified in blood culture, we changed his antibiotics to levofloxacin on day 7. He successfully recovered from the septic shock and dialysis was withdrawn.ConclusionsConsidering the use of inappropriate initial antibiotics, the early induction of PMX-DHP might have been a key determinant of his outcome. PMX-DHP therapy should be considered in septic shock in addition to antibiotic treatment.

Epidemiology of Febrile Neutropenia Episodes with Gram-Negative Bacteria Infection in Patients Who HaveUndergone Chemotherapy for Hematologic Malignancies: A Retrospective Study of 10 Years' Data from a Single Center.

BackgroundThe epidemiology of Gram-negative bacteria in patients with febrile neutropenia (FN) and their susceptibility to initial empirical antibiotic therapy is key to successful treatment during the treatment of hematologic malignancies.MethodsA retrospective study was conducted. Patients with FN and confirmed laboratory results of Gram-negative bacteria infections were included. If no direct sensitivity of the identified pathogen to the initially prescribed antibiotic regimen was confirmed, it was defined as inappropriate initial antibiotic treatment (IIAT).ResultsA total of 247 patients with FN were proven to be infected with Gram-negative bacteria, and 200 were diagnosed with acute leukemia. The most commonly detected bacteria were Escherichia coli (40%), Klebsiella pneumoniae (20%), and Pseudomonas aeruginosa (11%). In sum, 176 patients were classified as IIAT. The mortality rate in the IIAT group was significantly higher (37.7% vs 23.9%, P=0.038). With monotherapy as empirical treatment, high possibility of IIAT with fluoroquinolones (52%) and cephalosporins (35%) was detected, while more sensitivity to carbapenems (16%) and glycopeptides antibiotics (19%) was noticed. With combined treatment, cephalosporins/carbapenems had with the lowest percentage of IIAT (18%).ConclusionIn conclusion, inappropriate initial empirical antibiotic treatments were associated with higher mortality in patients with hematologic malignancies. The current empirical antibiotic regimen needs to be further optimized.

Does inappropriate initial antibiotic therapy affect in-hospital mortality of patients in the emergency department with Escherichia coli and Klebsiella pneumoniae bloodstream infections?

Extended-spectrum β-lactamase (ESBL)-positive bloodstream infection (BSI) is on the rise worldwide. The purpose of this study is to evaluate the impact of inappropriate initial antibiotic therapy (IIAT) on in-hospital mortality of patients in the emergency department (ED) with Escherichia coli and Klebsiella pneumoniae BSIs. This retrospective single-center cohort study included all adult patients with E. coli and K. pneumoniae BSIs between January 2007 and December 2013, who had undergone a blood culture test and initiation of antibiotics within 6 h of ED registration time. Multiple logistic regression was used to adjust for bacterial species, IIAT, time to antibiotics, age, sex, quick Sepsis Related Organ Failure Assessment (qSOFA) score ⩾ 2, and comorbidities. A total of 3533 patients were enrolled (2967 alive and 566 deceased, in-hospital mortality rate 16%). The patients with K. pneumoniae ESBL-positive BSI had the highest mortality rate. Non-survivors had qSOFA scores ⩾ 2 (33.6% vs 9.5%, P < 0.001), more IIAT (15.0% vs 10.7%, P = 0.004), but shorter mean time to antibiotics (1.70 vs 1.84 h, P < 0.001). A qSOFA score ⩾ 2 is the most significant predictor for in-hospital mortality; however, IIAT and time to antibiotics were not significant predictors in multiple logistic regression analysis. In subgroup analysis divided by qSOFA scores, IIAT was still not a significant predictor. Severity of the disease (qSOFA score ⩾ 2) is the key factor influencing in-hospital mortality of patients with E. coli and K. pneumoniae BSIs. The time to antibiotics and IIAT were not significant predictors because they in turn were affected by disease severity.

An easy-to-use scoring system for predicting bacteraemia with third-generation cephalosporin-resistant Enterobacterales in a low-resistance setting

Background: The incidence of third-generation cephalosporin-resistant Enterobacterales (3GCR-E) is increasing and a growing number of patients risk receiving inappropriate initial antibiotic treatment. Published scoring systems for predicting 3GCR-E bacteraemia are mostly based on studies from countries with a high incidence. In this study, we aimed to create an easy-to-use scoring system for predicting bacteraemia with these bacteria in a low-resistance setting.Materials and methods: Factors associated with 3GCR-E were studied retrospectively in a cohort of patients with Enterobacterales bacteraemia using uni- and multivariate analysis. A scoring system was constructed and was validated in a separate cohort of patients with Enterobacterales bacteraemia.Results: The derivation cohort comprised 625 cases of Enterobacterales bacteraemia. Three variables (previous hospital care abroad, 3GCR-E in a previous blood or urine culture and 3GCR-E in a previous rectal swab culture) were significantly associated with 3GCR-E bacteraemia. A scoring system, where at least one positive parameter equalled a positive score, was studied in the validation cohort, which comprised 675 cases of Enterobacterales bacteraemia. The sensitivity and specificity of the score were 53% and 95%, respectively. Positive and negative predictive values were 38% and 97%, respectively.Conclusions: This study presents an easy-to-use scoring system for predicting bacteraemia with 3GCR-E. The performance of the score is similar to that of several other, more complicated, scoring systems, developed in countries with higher rates of resistance. The minimal extra effort required to use this new score could facilitate its introduction into clinical routine.

Ignorance of pre-ED healthcare setting is a factor leading to inappropriate initial antibiotic treatment of sepsis in ED and poor outcomes in ICU.

Appropriate initial antibiotic therapy is critical for successfully treating sepsis. In the emergency department (ED), clinicians often rely on septic symptoms to guide empirical therapy. The aim of this study was to investigate whether history of contacting pre-ED healthcare setting is easy to be neglected and whether the patients received more inappropriate initial antibiotic therapy and developed poorer outcomes. Septic patients (n=453) admitted from ED to the intensive care unit (ICU) between 2014 and 2017 were retrospectively selected. Appropriate antibiotic treatment or not was determined by checking whether the selected antibiotics can effectively eradicate the bacteria identified. Various indexes were compared between patients with appropriate and inappropriate initial antibiotic treatments, including septic symptoms (qSOFA scores) in ED, septic-severity change in ICU (SOFA-score ratios), and septic outcomes (APACHE II scores, stay length, 30-day survival probability). These indexes were also compared between pre-ED healthcare and pre-ED community patients. In comparison with pre-ED community patients, pre-ED healthcare patients received more inappropriate initial antibiotic treatment in ED, showing poorer outcomes in ICU, including septic severity, stay-lengths in ICU and 30-day survival probabilities. Pre-ED settings is more significant than qSOFA scores to predict the inappropriate initial antibiotic treatment. Pre-ED healthcare settings, which are indexes for infection with antibiotic resistant pathogens, are easy to be neglected in the first hour in ED. We suggested that standard operating procedure for getting enough information of pre-ED settings should be incorporated to the 1h bundle of sepsis guideline.

Usefulness of Early C-Reactive Protein Kinetics in Response and Prognostic Assessment in Infected Critically Ill Patients: An Observational Retrospective Study.

The ideal biomarker to assess response and prognostic assessment in the infected critically ill patient is still not available.The aims of our study were to analyze the association between early C-reactive protein kinetics and duration and appropriatenessof antibiotic therapy and its usefulness in predicting mortality in infected critically ill patients. We have carried out an observational retrospective study in a cohort of 60 patients with community-acquiredpneumonia, aspiration pneumonia and bacteremia at an intensive care unit. We have collected C-reactive protein consecutive serumlevels for eight days as well as duration and appropriateness of initial antibiotic therapy. C-reactive protein kinetic groups were definedbased on the levels at days 0, 4 and 7. With a follow-up of one year, we have evaluated mortality at different time-points. We have obtained three different C-reactive protein kinetic groups from the sample: fast response, delayed but fast responseand delayed and slow response. We did not find statistically significant associations between C-reactive protein kinetics and early (intensivecare unit, hospital and 28-days) or late (six months and one year) mortality and antibiotic therapy duration (p > 0.05). Althoughthere were no statistically significant differences between the appropriateness of antibiotic therapy and the defined groups (p = 0.265),no patient with inappropriate antibiotic therapy presented a fast response pattern. Several studies suggest the importance of this protein in infection. Early C-reactive protein kinetics is not associated with response and prognostic assessment in infected critically ill patients.Nevertheless, a fast response pattern tends to exclude initial inappropriate antibiotic therapy.