Carbapenem Administration Research Articles

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.

A challenging case of carbapenem resistant Klebsiella pneumoniae-related pyogenic liver abscess with capsular polysaccharide hyperproduction: a case report

BackgroundCarbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a major public health problem, necessitating the administration of polymyxin E (colistin) as a last-line antibiotic. Meanwhile, the mortality rate associated with colistin-resistant K. pneumoniae infections is seriously increasing. On the other hand, importance of administration of carbapenems in promoting colistin resistance in K. pneumoniae is unknown.Case presentationWe report a case of K. pneumoniae-related pyogenic liver abscess in which susceptible K. pneumoniae transformed into carbapenem- and colistin-resistant K. pneumoniae during treatment with imipenem. The case of pyogenic liver abscess was a 50-year-old man with diabetes and liver transplant who was admitted to Abu Ali Sina Hospital in Shiraz. The K. pneumoniae isolate responsible for community-acquired pyogenic liver abscess was isolated and identified. The K. pneumoniae isolate was sensitive to all tested antibiotics except ampicillin in the antimicrobial susceptibility test and was identified as a non-K1/K2 classical K. pneumoniae (cKp) strain. Multilocus sequence typing (MLST) identified the isolate as sequence type 54 (ST54). Based on the patient’s request, he was discharged to continue treatment at another center. After two months, he was readmitted due to fever and progressive constitutional symptoms. During treatment with imipenem, the strain acquired blaOXA−48 and showed resistance to carbapenems and was identified as a multidrug resistant (MDR) strain. The minimum inhibitory concentration (MIC) test for colistin was performed by broth microdilution method and the strain was sensitive to colistin (MIC < 2 µg/mL). Meanwhile, on blood agar, the colonies had a sticky consistency and adhered to the culture medium (sticky mucoviscous colonies). Quantitative real-time PCR and biofilm formation assay revealed that the CRKP strain increased capsule wzi gene expression and produced slime in response to imipenem. Finally, K. pneumoniae-related pyogenic liver abscess with resistance to a wide range of antibiotics, including the last-line antibiotics colistin and tigecycline, led to sepsis and death.ConclusionsBased on this information, can we have a theoretical hypothesis that imipenem is a promoter of resistance to carbapenems and colistin in K. pneumoniae? This needs more attention.

Acquired Factor V Deficiency After Carbapenem Administration: A Case Report

Factor V (FV) deficiency is a coagulation disorder (congenital or acquired). Unlike congenital FV deficiency, mixing tests for prothrombin time and activated partial thromboplastin time are not corrected in acquired FV cases. A 79-year-old male was admitted to the intensive care unit after an emergency operation due to gastric ulcer perforation. While receiving antibiotic treatment for septic shock, the coagulation profile began to show prolongation of prothrombin time and activated partial thromboplastin time. FV deficiency (&lt; 1%) following meropenem administration was diagnosed . The patient did not show spontaneous bleeding or bleeding tendency. With fresh frozen plasma transfusion, steroid administration, and discontinuation of meropenem, the blood coagulation profile test result was normalized 20 days after diagnosis. His follow-up FV level increased to 78.7%. Although abnormalities in coagulation profiles are common in sepsis patients, in our patient, timely recognition and hematological consultation allowed early diagnosis and proper management of FV deficiency.

Impact of a multidisciplinary management team on clinical outcome in ICU patients affected by Gram-negative bloodstream infections: a pre-post quasi-experimental study

BackgroundBloodstream infections (BSIs) by Gram-negative pathogens play a major role in intensive care patients, both in terms of prevalence and severity, especially if multi-drug resistant pathogens are involved. Early appropriate antibiotic therapy is therefore a cornerstone in the management of these patients, and growing evidence shows that implementation of a multidisciplinary team may improve patients’ outcomes. Our aim was to evaluate the clinical and microbiological impact of the application of a multidisciplinary team on critically ill patients.MethodsPre-post study enrolling critically ill patients with Gram negative bloodstream infection in intensive care unit. In the pre-intervention phase (from January until December 2018) patients were managed with infectious disease consultation on demand, in the post-intervention phase (from January until December 2022) patients were managed with a daily evaluation by a multidisciplinary team composed of intensivist, infectious disease physician, clinical pharmacologist and microbiologist.ResultsOverall, 135 patients were enrolled during the study period, of them 67 (49.6%) in the pre-intervention phase and 68 (50.4%) in the post-intervention phase. Median age was 67 (58–75) years, sex male was 31.9%. Septic shock, the need for continuous renal replacement therapy and mechanical ventilation at BSI onset were similar in both groups, no difference of multidrug-resistant organisms (MDRO) prevalence was observed. In the post-phase, empirical administration of carbapenems decreased significantly (40.3% vs. 62.7%, p = 0.02) with an increase of appropriate empirical therapy (86.9% vs. 55.2%, p < 0.001) and a decrease of overall antibiotic treatment (12 vs. 16 days, p < 0.001). Despite no differences in delta SOFA and all-cause 30-day mortality, a significant decrease in microbiological failure (10.3% vs. 29.9%, p = 0.005) and a new-onset 30-day MDRO colonization (8.3% vs. 36.6%, p < 0.001) in the post-phase was reported. At multivariable analysis adjusted for main covariates, the institution of a multidisciplinary management team (MMT) was found to be protective both for new MDRO colonization [OR 0.17, 95%CI(0.05–0.67)] and microbiological failure [OR 0.37, 95%CI (0.14–0.98)].ConclusionsThe institution of a MMT allowed for an optimization of antimicrobial treatments, reflecting to a significant decrease in new MDRO colonization and microbiological failure among critically ill patients.

Evaluating Clinical Sequelae of the Carbapenem-Valproate Interaction: A Retrospective Analysis.

Previous studies identified a rapid decrease in valproate serum concentrations when coadministered with a carbapenem; however, the specific consequences and subsequent therapy adjustments are not well described. We aimed to investigate the clinical and therapeutic implications of the carbapenem-valproate drug-drug interaction. This retrospective analysis included data from 2 large academic medical centers during January 2017 to June 2022. The primary outcome was incidence of seizures or behavioral events stratified by valproate indication. All adult patient encounters with concomitant administration of any carbapenem antimicrobial and valproate were included. Patients without prolonged exposure to valproate prior to hospitalization, without valproate levels pre- and post-carbapenem administration, with an admitting diagnosis of seizure, with exposure to other agents that decrease valproate concentrations, or who had a seizure during the hospitalization prior to carbapenem exposure were excluded. Two hundred fifty-eight episodes of concomitant use among 78 unique adult patients were included. Valproate was used for seizure control in 41 patients (52.6%) and for mood-related disorders in 37 (47.4%). In those prescribed valproate for its antiepileptic properties, seizures occurred following carbapenem administration in 46.3% of encounters. In those taking valproate for mood-related disorders, 50.8% met the primary endpoint of behavioral disturbance. Our study demonstrates significant clinical implications of the carbapenem-valproate interaction. Clinicians should be aware of this interaction and consider alternative antimicrobial and/or antiepileptic agents whenever possible. Adding or increasing doses of antiepileptic agents and/or consultation with a neurologist prior to concomitant use should be considered when this combination cannot be avoided.

Modelling interventions and contact networks to reduce the spread of carbapenem-resistant organisms between individuals in the ICU

Contact precautions are widely used to prevent the transmission of carbapenem-resistant organisms (CROs) in hospital wards. However, evidence for their effectiveness in natural hospital environments is limited. To determine which contact precautions, healthcare worker (HCW)-patient interactions, and patient and ward characteristics are associated with greater risk of CRO infection or colonization. CRO clinical and surveillance cultures from two high-acuity wards were assessed through probabilistic modelling to characterize a susceptible patient's risk of CRO infection or colonization during a ward stay. User- and time-stamped electronic health records were used to build HCW-mediated contact networks between patients. Probabilistic models were adjusted for patient (e.g. antibiotic administration) and ward (e.g. hand hygiene compliance, environmental cleaning) characteristics. The effects of risk factors were assessed by adjusted odds ratio (aOR) and 95% Bayesian credible intervals (CrI). The degree of interaction with CRO-positive patients, stratified by whether CRO-positive patients were on contact precautions. The prevalence of CROs and number of new carriers (i.e. incident CRO aquisition). Among 2193 ward visits, 126 (5.8%) patients became colonized or infected with CROs. Susceptible patients had 4.8 daily interactions with CRO-positive individuals on contact precautions (vs 1.9 interactions with those not on contact precautions). The use of contact precautions for CRO-positive patients was associated with a reduced rate (7.4 vs 93.5 per 1000 patient-days at risk) and odds (aOR 0.03, 95% CrI 0.01-0.17) of CRO acquisition among susceptible patients, resulting in an estimated absolute risk reduction of 9.0% (95% CrI 7.6-9.2%). Also, carbapenem administration to susceptible patients was associated with increased odds of CRO acquisition (aOR 2.38, 95% CrI 1.70-3.29). In this population-based cohort study, the use of contact precautions for patients colonized or infected with CROs was associated with lower risk of CRO acquisition among susceptible patients, even after adjusting for antibiotic exposure. Further studies that include organism genotyping are needed to confirm these findings.

Implementation of an antimicrobial stewardship program in the Vascular Surgery ward of a university tertiary care hospital in Pavia, Northern Italy

PurposeThe commitment of multidisciplinary teams in antimicrobial stewardship programs (ASPs) is often inadequately considered, especially in surgical wards. We wanted to evaluate clinical, microbiological, and pharmacological outcomes before and after the implementation of an ASP in the Vascular Surgery ward of Fondazione IRCCS Policlinico San Matteo, a tertiary care hospital in Pavia, Italy.MethodsThis was a quasi-experimental quality-improvement study. The antimicrobial stewardship activity was conducted twice a week for 12 months and consisted of both prospective audit and feedback of all the ongoing antimicrobial prescriptions by the infectious diseases’ consultants and educational meetings for the healthcare workers of the Vascular Surgery ward. For comparison between the study periods, Student t test (Mann–Whitney test for skewed distributions) was used for quantitative variables (ANOVA or Kruskall-Wallis for > 2 groups respectively), and Pearson’s chi-squared test (Fisher exact test where appropriate) for categorical variables. 2-tailed tests were used. P-value significance cut-off was 0.05.ResultsDuring the 12-month intervention period, among a total number of 698 patients, 186 prescriptions were revised, mostly leading to de-escalating an ongoing antimicrobial therapy (39, 20.97%). A statistically significant reduction in isolates of carbapenem-resistant Pseudomonas aeruginosa (p-value 0.003) and the absence of Clostridioides difficile infections were reported. No statistically significant changes were observed in terms of length of stay and all-cause in-hospital mortality. A significant decrease in the administration of carbapenems (p-value 0.01), daptomycin (p-value < 0.01) and linezolid (p-value 0.43) was registered. A significant reduction in antimicrobial costs was also observed.ConclusionsThe implementation of a 12-month ASP brought significant clinical and economic results, highlighting the benefits of a multidisciplinary teamwork.

Intestinal Colonization of Preterm Neonates with Carbapenem Resistant Enterobacteria at Hospital Discharge

Our aim was to investigate gut colonization with carbapenem-resistant Enterobacterales (CRE) in the population of preterm neonates at discharge from a tertiary care center in Serbia. The study included 350 randomly selected neonates/infants discharged in the period April 2018-May 2019. CRE colonization was present in 88/350 (25.1%) of patients. Klebsiella pneumoniae producing KPC and OXA-48 carbapenemase were detected in 45 and 42 subjects, respectively, while NDM producing Escherichia coli was identified in one patient only. All OXA-48 strains harbored blaCTX-M-15, while both blaTEM and blaSHV were present in all but one KPC-producing strain. CRE isolates exhibited a multidrug resistance pattern with uniform fluoroquinolone resistance, universal susceptibility to colistin, and variable susceptibility to aminoglycosides. Administration of carbapenems was common (~50%) and it was strongly associated with colonization, as well as the combinational therapeutic regimens that included meropenem, contrary to ampicillin-sulbactam/colistin therapy and prolonged course of the initial therapy (ampicillin/amikacin ≥ 7 days). Other risk factors for CRE carriage were level of immaturity, admission to neonatal intensive care unit, prolonged hospitalization and invasive procedures. Although the rate of clinically and/or laboratory proven systemic infections was significantly higher among colonized patients, CRE infection was confirmed in one patient only (1.1%) that was colonized with NDM E. coli. Clonal relatedness of CRE isolates was high, with seven and eight clusters detected among KPC (N = 30) and OXA-48 (N = 37) producing strains, respectively. The follow up of the 31 KPC-colonized patients after discharge from hospital revealed common decolonization within one month (~68%). In conclusion, our results demonstrated a high rate of CRE colonization that is most likely related to carbapenem consumption and lack of screening as important infection prevention practice.

The epidemiology of bloodstream infection contributing to mortality: the difference between community-acquired, healthcare-associated, and hospital-acquired infections

BackgroundThe epidemiology of bloodstream infection (BSI) is well-established; however, little is known about the contribution of different pathogens to mortality. To understand true burden of BSI, pathogens contributing to mortality were investigated and compared according to where the BSI was acquired.MethodsData from deceased patients in two teaching hospitals in the Republic of Korea were collected. BSI contributing mortality was defined as BSI within 2-weeks before death. Cases were grouped by acquisition sites: community-acquired (CA)-, healthcare-associated (HCA)-, and hospital-acquired (HA)-BSI. Drug resistance, BSI focus, and appropriateness of empirical antimicrobial therapy were also compared.ResultsAmong 1849 deceased patients in the hospitals, 280 (15.1%) patients experienced BSI within 2-weeks before death. In all, 71, 53, and 156 patients in the CA-, HCA-, and HA-BSI groups, respectively, with 316 total isolated pathogens were analyzed. The three most common pathogens were Klebsiella pneumoniae (17.1%), Escherichia coli (16.4%), and Staphylococcus aureus (11.4%). While K. pneumoniae and E. coli were the most common pathogens in CA- and HCA-BSI, Acinetobacter baumannii and Candida species were in HA-BSI. 26.3% (41/156) of patients experienced breakthrough HCA-BSI during administration of carbapenem and/or vancomycin. The proportion of central venous catheter-related infection (0%, 3.4% and 28.3%), carbapenem resistant-Gram negative bacilli (0%, 6.9% and 21.9%), and inappropriate empirical antimicrobial therapy (21.1%, 37.7% and 51.9%; all P < 0.001) were more frequently observed in HA-BSI.ConclusionThe epidemiology of BSI related to mortality had unique characteristics according to the acquisition site. Given the epidemiology of HA-BSI, infection control and antibiotics stewardship programs should be emphasized.

A Retrospective Case Series of Concomitant Carbapenem and Valproic Acid Use: Are Best Practice Advisories Working?

Background: A Best Practice Advisory (BPA) warns clinicians of an interaction between carbapenems and valproic acid (VPA) that can cause significant declines in VPA levels leading to serious consequences for patients treated for seizure disorder and unknown implications for alternative indications. Objective: The goal of this study was to assess BPA efficacy in avoiding concomitant VPA/carbapenems, and to characterize use of these agents, clinical implications, and potential alternative therapeutic options. Methods: Retrospective chart review was performed on all patients over the course of 1 year who were concomitantly prescribed a carbapenem and VPA at Hartford Hospital, Hartford, CT. Data collected included: level of care, duration of concomitant therapy, indications, VPA levels during or surrounding overlap, documentation of the interaction, and therapeutic implications. Results: Carbapenems and VPA were administered to 591 and 625 patients, respectively; the BPA fired 126 times in 24 patients, and 15 patients were initiated on these agents concomitantly. Eight (53%) patients received VPA for seizures. The remaining seven (47%) received VPA for alternative indications. Eight of nine VPA levels were sub-therapeutic during carbapenem therapy and polypharmacy was administered in all patients receiving VPA for non-convulsive indications. Conclusion: Co-prescribing of these drugs was rare; however, the BPA was ineffective in 63% of instances. Reductions in VPA efficacy for any indication should be expected with concomitant carbapenem administration. Antibiotics other than carbapenems should be considered when coverage of multidrug resistant Gram-negative pathogens is required in patients whose VPA treatment cannot be interrupted or switched to a therapeutic alternative.

Usefulness analysis of the 2018 ASCO/IDSA guideline for outpatient management of fever and neutropenia in adults treated for malignancy

Although the clinical practice guideline for outpatient management of febrile neutropenia (FN) in adults treated for malignancy was updated by the ASCO/IDSA in 2018, most patients with FN in our hospital have been hospitalized. We performed this study to analyze the usefulness of the guideline. The medical records of patients hospitalized for FN in Kyungpook National University Chilgok Hospital from May 2016 to April 2018 were retrospectively reviewed. The feasibility of candidates for outpatient management according to the guideline was evaluated based on the outcomes. A total of 114 patients were enrolled and categorized into two groups, low-risk (38.6%) and high-risk (61.4%). The proportion of feasible candidates for outpatient management was 70.2% and was higher in the low-risk than in the high-risk group (90.0% vs. 57.1%; P < 0.001). The low-risk group had no mortality, no resistance to oral amoxicillin/clavulanate or ciprofloxacin, a higher rate of successful empirical antibiotics, and lower rates of glycopeptide or carbapenem administration. A significant number of hospitalized cancer patients treated for FN after chemotherapy were found to be feasible candidates for outpatient management. The guideline can be a useful tool to reduce labor of healthcare workers and hospitalization costs.

Vancomycin Associated Acute Kidney Injury: A Longitudinal Study in China.

Background: Vancomycin-associated acute kidney injury (VA-AKI) is a recognizable condition with known risk factors. However, the use of vancomycin in clinical practices in China is distinct from other countries. We conducted this longitudinal study to show the characteristics of VA-AKI and how to manage it in clinical practice. Patients and Methods: We included patients admitted to hospital, who received vancomycin therapy between January 1, 2016 and June 2019. VA-AKI was defined as a patient having developed AKI during vancomycin therapy or within 48 h following the withdrawal of vancomycin therapy. Results: A total of 3719 patients from 7058 possible participants were included in the study. 998 patients were excluded because of lacking of serum creatinine measurement. The incidence of VA-AKI was 14.3%. Only 32.3% (963/2990) of recommended patients performed therapeutic drug monitoring of vancomycin. Patients with VA-AKI were more likely to concomitant administration of cephalosporin (OR 1.55, 95% CI 1.08–2.21, p = 0.017), carbapenems (OR 1.46, 95% CI 1.11–1.91, p = 0.006) and piperacillin-tazobactam (OR 3.12, 95% CI 1.50–6.49, p = 0.002). Full renal recovery (OR 0.208, p = 0.005) was independent protective factors for mortality. Compared with acute kidney injury stage 1, AKI stage 2 (OR 2.174, p = 0.005) and AKI stage 3 (OR 2.210, p = 0.005) were independent risk factors for fail to full renal recovery. Conclusion: Lack of a serum creatinine measurement for the diagnosis of AKI and lack of standardization of vancomycin therapeutic drug monitoring should be improved. Patient concomitant with piperacillin-tazobactam are at higher risk. Full renal recovery was associated with a significantly reduced morality.

Interactions between carbapenems and valproic acid among the patients in the intensive care units.

To evaluate risk factors for epileptic seizures or status epilepticus (SE) in patients concomitantly receiving valproic acid (VPA) and carbapenems. Adult patients in the intensive care units (ICUs) who concomitantly received VPA and carbapenems from 2007 to 2017 were included. The impacts of different carbapenems on serum concentration of VPA were compared. Among 162 patients included, 104 (64.2%) and 45 (27.8%) developed epileptic seizures and SE, respectively. The risk factors for epileptic seizures were age (per year increase, adjusted odds ratio [aOR], 1.03), initial antiepileptic regimen (monotherapy and polytherapy, aOR, 0.43 and 0.18, respectively), and VPA serum concentration after concomitant carbapenem administration (per 1μg/mL increase, aOR, 0.96). VPA serum concentration after concomitant carbapenem administration was an independent risk factor for SE (per μg/mL increase, aOR, 0.98). Concomitant imipenem/cilastatin administration did not significantly decrease VPA serum concentration compared to that by meropenem or ertapenem. The length of stay and number of days on ventilation after concomitant carbapenem administration in the ICUs were significantly more in those with epileptic seizures or SE. Carbapenems decreased VPA serum concentration and increased the risk of epileptic seizures and SE, which led to increased length of ICU stay.

Epidemiology and risk factors for healthcare-associated infections caused by Pseudomonas aeruginosa

Pseudomonas aeruginosa (PA) is a globally recognized cause of healthcare-associated infections (HAIs). The aim of our cross-sectional study, conducted in a Serbian tertiary care hospital, was to investigate clinical characteristics of HAIs caused by the PA, the prevalence of various drug-resistant phenotypes of this pathogen, and risk factors for their occurrence. Prolonged ICU stay and previous carbapenem administration were independent risk factors for HAIs caused by carbapenem-resistant PA, while HAIs caused by multidrug-resistant PA were more frequent in patients with prolonged stay in an ICU, who were previously hospitalized at another department and previously treated with aminoglycosides, fluoroquinolones or glycopeptides. The prolonged ICU stay was the only significant risk factor for HAIs caused by extensively drug-resistant PA. To decrease the incidence of HAIs caused by drug-resistant PA, a multifaceted approach is necessary, including staff education, antibiotic stewardship, improving hygiene, shortening hospitalization, and minimizing exposure to invasive medical procedures/devices.

Carbapenems Utilization Evaluation in Neutropenic Patients of a Teaching Hospital

Background: Carbapenems is frequently prescribed for treatment or prophylaxis in neutropenic patients. It is cleared that antimicrobial misuse can cause poor patient outcomes, through raise of antibiotic resistance, increased adverse events, and prolonged length of hospital stay. To evaluate the rational use of Imipenem- Cilastatin and Meropenem for empirical antibacterial therapy in neutropenic patients based on IDSA guideline. Methods: Through this cross-sectional study, we assessed the appropriateness of administration of Carbapenems in neutropenic patients admitted in hematology–oncology and bone marrow transplant wards in Namazee hospital, Shiraz, Iran, from March 2012 to May 2013. Results: Total of 90 patients was enrolled. Drug therapy duration was appropriate in 69.6% of Imipenem-Cilastatin and 75% of Meropenem groups. Sampling time of culture was appropriated in 59.1% of Imipenem-Cilastatin and 78.3% of Meropenem group, interval of drug administration was correct in 74.5% at initiation and 79.4% during therapy in Imipenem-Cilastatin group. For dosing these values were 74.5% and 72.2%, respectively. These values were evaluated in patients who received Meropenem too, interval was correct in 89.5% at initiation and 90.3% during therapy, dosing was correct in 12.3% both at initiation and during therapy. Conclusion: These finding suggest that attention to correct dose, correct interval, renal dose adjustment, logical indication for administration of Carbapenem should be considered by health care system. J Pharm Care 2019; 7(4): 106-111.

Evaluation of Intervention by an Antimicrobial Stewardship Team for Patients with Bacteremia

In this study, antimicrobial stewardship team (AST) intervention was evaluated by comparing patient outcomes and consumption of broad-spectrum antibiotics [carbapenem antibiotics and tazobactam/piperacillin (TAZ/PIPC)] before and after the intervention. There was no fluctuation in the consumption rate of carbapenem, TAZ/PIPC and other antibiotics, but there was a decreased annual consumption of antibiotics after AST intervention compared to before intervention. For the carbapenems, antimicrobial use density (AUD) of meropenem (MEPM) was highest in both periods, at 20.1 and 20.4 before and after AST intervention, respectively, with no significant change after AST intervention. However, the days of therapy (DOT) for MEPM were 27.4 and 24.8 d, respectively, with a decreasing trend after AST intervention. AUD and DOT for TAZ/PIPC after AST intervention were 6.5 and 8.1 d, respectively, which were lower than the pre-intervention values. Rapid identification of the causative strain enables early de-escalation and may improve the economics of antibiotic use, but there was no difference from before to after AST intervention. Compared with before and after strain identification, the carbapenem administration rate after AST intervention was significantly lower than the pre-intervention rate (p<0.01). There was no difference in 28-day mortality and treatment period before and after AST intervention, and there were no differences in outcomes such as resolution of bacteremia, mortality, exacerbation and no change from before to after AST intervention. Based on these results, we suggest that AST intervention can reduce consumption of antibiotics without altering patient outcomes.

Risk factors for the first episode of Acinetobacter baumannii resistant to colistin infection and outcome in critically ill patients.

Introduction To identify risk factors for the first episode of Acinetobacter baumannii resistant to colistin (ABCR) infection in critically ill patients.Aim Prospective observational study.Methodology ICU patients who required mechanical ventilation for >48 h during a 36 month period. Clinical and microbiological data were studied; characteristics of patients infected with ABCR were compared with those of critically ill patients who presented infection due to A. baumannii sensitive to colistin (ABCS).Results Twenty patients presented with ABCR infection, and 57 patients ABCS infection. Compared to patients with ABCS infection, patients suffering from ABCR infection had received more frequent and/or for longer duration dosing of several antibiotics active against Gram-negative bacteria (P<.05). Moreover, the duration of mechanical ventilation, and the presence of invasive procedures and tracheostomy prior to infection were associated with ABCR infections. The duration of carbapenem administration was an independent risk factor for ABCR infection [odds ratio (OR), 1.21; 95 % confidence interval (95 %, CI), 1.00 to 1.45; P=.049]. Mortality rate for patients with ABCR infection was higher (85 vs 39 % for the ABCS group). Sequential organ failure assessment score on admission, Charlson score and ABCR infection were independent risk factors for mortality.Conclusion ABCR infection is a life-threatening infection, which might be more common in patients with previous use of antibiotics, especially carbapenems.

Increasing burden of biliary tract infection caused by extended-spectrum beta-lactamase-producing organisms in Korea: A nationwide population-based study.

Biliary tract infections (BTIs) are a major cause of bacteremia. The prevalence of antibiotic-resistant pathogens in BTI patients is reported to be increasing. We used a nationwide database to evaluate the prevalence of, and risk factors for, BTIs caused by extended-spectrum beta-lactamase-producing organisms (ESBL-PO) in Korea. Patients with a BTI diagnosis, an admission history, a history of a BTI-related procedure, and antibiotic use for ≥4days between 2007 and 2016 were identified from the Health Insurance Review and Assessment Service database. A BTI treated with carbapenems (BTI-TC) was used as the surrogate for a BTI caused by ESBL-PO. We conducted a multivariate logistic regression analysis to determine the risk factors for BTI-TC. In total, 341002 patients were enrolled. The overall percentage of BTI-TC among BTIs was 2.4%, with an increasing annual trend (P<0.0001). The risk of acute cholangitis caused by ESBL-PO increased significantly in men, older patients, patients with comorbidities, patients with a history of a biliary procedure within the previous year, and patients with a history of antibiotic use within the previous 90days. Regarding antibiotic use, the patients at highest risk were those previously prescribed carbapenems (adjusted odds ratio, 4.77; P<0.0001). The prevalence of BTIs caused by ESBL-PO has increased during the last 10years. Initial carbapenem therapy should be considered for elderly patients with acute cholangitis if they have had a previous biliary procedure and/or a history of carbapenem administration within the previous 90days.

Overuse of antianaerobic drug is associated with poor postchemotherapy prognosis of patients with hepatocellular carcinoma.

Overuse of antibiotic drugs alters the composition of gut microbiota and has detrimental effects on the host. In our study, we investigated association of gut flora and antibiotics in the prognosis of patients with liver cancer who have undergone chemotherapy by analyzing two independent clinical studies. We retrospectively subanalyzed a previously reported randomized controlled trial (RCT) on hepatic arterial infusion chemotherapy in patients with hepatocellular carcinoma (HCC) to investigate the association between use of antibiotics and prognosis. In the other study, we prospectively determined the abundance of specific bacterial genus in patients with HCC by sequencing 16S ribosomal RNA and assessed its association with survival. Subanalysis of the RCT data showed that, of 26 types of antibiotics used, administration of carbapenem before or during chemotherapy was associated with poor progression‐free survival (PFS) and overall survival (OS) of patients with HCC (carbapenem + vs. −; median PFS, 78 days vs. 154 days, p = 0.0053; median OS, 177 days vs. 475 days, p = 0.0003). Multivariate analysis revealed that antianaerobic drug use is an independent predictor of poor prognosis. In the prospective study, the abundance of Blautia in fecal microbiota correlated positively with both PFS and OS of patients with HCC who underwent chemotherapy. Use of antibiotics targeting anaerobes is associated with a poor prognosis in patients with HCC who have undergone chemotherapy, whereas the intestinal anaerobic bacteria, Blautia is associated with a good prognosis. These findings might indicate the need for caution regarding overuse of broad‐spectrum antibiotics targeting anaerobes in patients with HCC.

Risk factors for extended-spectrum beta-lactamase-producing Enterobacteriaceae infection causing septic shock in cancer patients with chemotherapy-induced febrile neutropenia.

Patients with chemotherapy-induced febrile neutropenia (FN) are vulnerable to extended-spectrum b-lactamase-producing Enterobacteriaceae (ESBL-PE) infection. Early identification of patients suspected to have ESBL-PE infection for empirical carbapenem administration is crucial; nevertheless, risk factors for ESBL-PE causing septic shock remain unclear. We identify factors to predict ESBL-PE in septic shock patients with chemotherapy-induced FN. In this observational, prospectively collected registry-based study, consecutive adult chemotherapy-induced FN patients with septic shock who were admitted to the emergency department between June 2012 and June 2018 were enrolled. Clinical and laboratory data extracted from the septic shock registry were assessed to identify risk factors for ESBL-PE. Of 179 chemotherapy-induced FN septic shock patients, ESBL-PE is isolated in 23 (12.8%). ESBL-PE infection is frequently seen in patients with hepatobiliary cancer (17.4% vs. 4.5%, P = 0.037), leukemia (13.0% vs. 2.6%, P = 0.046), and those with profound neutropenia (defined as absolute neutrophil count < 100) (73.9% vs. 43.6%, P = 0.007) in contrast to those with lung cancer (0% vs. 14.7%, P = 0.048) and other solid cancer (0% vs. 19.2%, P = 0.016). Multivariate logistic regression reveals that profound neutropenia (adjusted OR 3.67; 95% CI 1.372-9.799; P = 0.010) is an independent risk factor for ESBL-PE infection after adjusting age, the presence of solid tumor, and the parameters of sepsis severity scores. ESBL-PE is rare (12.9%) in chemotherapy-induced FN patients with septic shock. Early empirical carbapenem therapy might be considered in chemotherapy-induced FN patients with profound neutropenia.