Antimicrobial Resistance Of Major Pathogens Research Articles

142. Effect of Discontinuation of Antimicrobial Stewardship Programs on the Antibiotic Usage Pattern and Incidence of Antibiotic Resistance in the Major Bacterial Species

BackgroundThe aim of this study was to analyze the effect of discontinuation of antimicrobial stewardship programs (ASP) activity on the antibiotic usage pattern.MethodsAn interrupted time series analysis assessing the trends in antibiotic use and incidence of antimicrobial resistance in major pathogens was conducted between March 2017 and April 2019 in an 859-bed university-affiliated hospital in Korea, where all ASP activities were discontinued in February 2018. The major activity of the ASP was a restrictive measure for designated antibiotics. We defined antibiotics as medication with the Anatomical Therapeutic Chemical class J01, and the antibiotic consumption was measured as days of therapy (DOT), which was then standardized per 1,000 patient-days. ResultsThe use of antibiotics against multidrug-resistant pathogens increased immediately after the discontinuation of restrictive antibiotic program (41.01 and 150.99 days of therapy [DOT]/1,000 patient-days in the general ward [GW] and intensive care unit [ICU], respectively). In addition, there were positive changes for the GW and ICU (4.20 and 31.57 DOT/1,000 patient-days per month, respectively). The use of broad-spectrum antibiotics in patients in the ICU significantly decreased (-674.26 DOT/1,000 patient-days). For non-broad-spectrum antibiotics, there were positive changes for the GW and ICU (18.17 and 22.69 DOT/1,000 patient-days per month, respectively. ConclusionIn conclusion, after discontinuation of ASP, antibiotic usage patterns rapidly returned to the patterns prior to ASP implementation.Disclosures All Authors: No reported disclosures

Analysis of pathogen spectrum and antimicrobial resistance of pathogens associated with hospital-acquired infections collected from 11 teaching hospitals in 2018

Objective: To investigate the spectrum and antimicrobial resistance of major pathogens causing nosocomial infections in China, 2018. Methods: Non-duplicated nosocomial cases as well as pathogens causing bloodstream infections (BSI), hospital-acquired pneumonia (HAP) and intra-abdominal infections (IAI) from 11 teaching hospitals across China were collected. The minimum inhibitory concentrations (MICs) of clinically significant strains were determined by agar dilution method or broth microdilution method. The Clinical and Laboratory Standards Institute (CLSI) M100-S29 criteria were used for interpretation, and the WHONET-5.6 software was used in data analysis. Results: A total of 1 590 cases were collected, including 831 cases from BSI, 450 cases from HAP and 309 cases from IAI. The most prevalent pathogens causing BSI were Escherichia coli (29.2%, 243/831), Klebsiella pneumoniae (16.2%, 135/831) and Staphylococcus aureus (10.1%, 84/831); the most prevalent pathogens causing IAI were E. coli (26.2%, 81/309), Enterococcus faecium (15.5%, 48/309) and K. pneumoniae (13.3%, 41/309); while Acinetobacter baumanii (24.7%, 111/450), Pseudomonas aeruginosa (20.7%, 93/450) and K. pneumoniae (16.2%, 73/450) were dominated in HAP. All S. aureus were susceptible to tigecycline, linezolid, daptomycin and glycopeptides; 77.8% (105/135) of S. aureus strains were susceptible to ceftaroline. Methicillin-resistant S. aureus (MRSA) accounted for 29.6% (40/135) of all the S. aureus, and was lower than the accounted rate of methicillin-resistant coagulase-negative Staphylococcus (MRCNS) (83.7%, 41/49). One E. faecium strain (1.1%, 1/95) resistant to vacomycin and teicoplanin and one E. faecalis strain (2.3%, 1/43) resistant to linezolid was found. The prevalence of extended-spectrum β-lactamase (ESBL) was 56.1% (193/344) in E. coli and 22.1% (55/249) in K. pneumonia; the rate of carbapenem resistant E. coli and K. pneumonia was 4.1% (14/344) and 22.9% (57/249), respectively; the percentage of ceftazidime/avibactam resistant E. coli and K. pneumonia was 2.3% (8/344) and 2.0% (5/249), respectively; the percentage of colistin resistant E. coli and K. pneumonia was 1.5% (5/344) and 7.6% (19/249), respectively; no E. coli and K. pneumonia strains were found resistant to tigecycline. The rate of carbapenem resistant A. baumanii and P. aeruginosa were 78.9% (146/185) and 36.7% (66/180), respectively. A. baumanii showed low susceptibility to the antimicrobial agents except colistin (99.5%, 184/185) and tigecycline (91.4%, 169/185). Colistin, amikacin and ceftazidime/avibactam demonstrated high antibacterial activity against P. aeruginosa with susceptility rate of 100% (180/180), 93.3% (168/180) and 85.6% (154/180), respectively. Conclusions: Nosocomial Gram-negative pathogens show high susceptibilities to tigecycline, colistin and ceftazidime/avibactam in vitro. Antimicrobial resistance in A. baumannii is a serious problem. The prevalence of carbapenem-resistant Enterobacteriaceae has increased, which should be monitored continuously in China.

Literature review on the distribution characteristics and antimicrobial resistance of bacterial pathogens in neonatal sepsis

Purpose Neonatal sepsis (NS) has no specific clinical manifestations and blood culture analysis requires a long period of time. Knowledge of prevalent bacterial isolates and their antibiotic susceptibility is crucial when choosing an empirical therapy to decrease morbidity and mortality. This literature review summarizes the distribution characteristics and antimicrobial resistance of bacterial pathogens associated with bloodstream infections in Chinese neonates, and thus serves as a reference for pediatricians. Methods The full-text journal database, CNKI, was searched using the key words “neonatal”, “sepsis”, and “bacterial pathogen” to retrieve relevant literature published from 2016 up to April 2018. The following data were extracted from the selected papers: title, pathogen collection time, care unit name, province (city), distribution of bacterial pathogens among bloodstream infections, and antimicrobial resistance of major pathogens. Results A total of 86 articles were searched, of which 30 complied with the study requirements and thus were included in the review; all were retrospective studies. The articles covered a total of 4098 bacterial strains from 24 cities (2494 Gram-positive bacteria, 1429 Gram-negative bacteria, 176 fungi). Among the Gram-positive bacteria, the four pathogens with the highest detection rates were coagulase-negative staphylococci (CoNS) (40.23%), Streptococci (6.81%), Enterococci (6.10%), and Staphylococcus aureus (S. aureus) (5.15%); among the Gram-negative bacteria, Klebsiella (14.52%), Escherichia coli (12.12%), Enterobacter cloacae (1.90%), and Pseudomonas (1.41%) had the highest detection rates. The detection rate of Candida and other fungi was 4.29%. Among the pathogens with high clinical detection rates, S. epidermidis and S. aureus are highly resistant to both erythromycin and penicillin. Antibacterial drugs with high efficacy for both S. epidermidis and S. aureus include vancomycin, ciprofloxacin, gentamicin, linezolid, rifampicin, and tetracycline. Klebsiella pneumoniae and Escherichia coli are highly resistant to ampicillin, but there are drugs with high efficacy for both, including imipenem, piperacillin/tazobactam, aminoglycosides (gentamicin, amikacin), and quinolones (levofloxacin, ciprofloxacin). In contrast to the drug resistance data reported by the China Antimicrobial Resistance Surveillance System (CARSS) in 2017, the detection rate of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCoNS) in the blood cultures of neonates with sepsis exceeded the national average drug resistance level (p < .01). The resistance rate of K. pneumoniae to third-generation cephalosporins was higher than the national average drug resistance level (p < .01), but this organism was most sensitive to carbapenems (carbapenem resistance refers to resistance to any of imipenem, meropenem, or ertapenem). The resistance of Escherichia coli to quinolones was better than the national average level (p < .01). Conclusions Medical care-related infections in neonatal intensive care units (NICUs) were more often caused by CoNS than by S. aureus and Gram-negative bacteria. Vancomycin remains the preferred drug for treating confirmed infections, because most isolated CoNS are resistant to β-lactam drugs including penicillin. For Gram-negative enteric bacteria, aminoglycoside and carbapenem were sufficient for treatment. Compared to the CARSS data on bacterial resistance, the data in this review on the resistance of pathogens causing NS were not favorable. The next goal in antibiotic management in NICUs must be to develop strategies to reduce the use of antibiotics.

A multicenter epidemiology study on the risk factors and clinical outcomes of nosocomial intra-abdominal infections in China: results from the Chinese Antimicrobial Resistance Surveillance of Nosocomial Infections (CARES) 2007-2016.

ObjectiveThis study aimed to determine the risk factors for intra-abdominal infections (IAIs), assess the clinical outcomes of IAIs, and investigate the spectrum and antimicrobial resistance of major pathogens causing IAIs.Patients and methodsThis prospective observational study enrolled patients from the Chinese Antimicrobial Resistance Surveillance of Nosocomial Infections (CARES) program between 2007 and 2016. Data on the clinicopathological factors and causative pathogens were collected. The results of antimicrobial susceptibility tests were interpreted according to the minimum inhibitory concentration (MIC) interpretive breakpoints recommended by the Clinical and Laboratory Standards Institute in 2017.ResultsA total of 2,756 patients were included. The 30-day all-cause mortality was 9.5% (262/2,756). Multivariable analysis showed that the following independent risk factors were associated with the 30-day mortality: age >60 years, pulmonary disease, tracheal cannula, infection occurring in intensive care unit (ICU), prior admission within 3 months, antibiotic use before infection, recent use of immunosuppressants, and multidrug-resistant organisms. In addition, 2,913 clinical isolates were collected. The Gram-negative and Gram-positive bacteria accounted for 70.8% and 29.2% of all isolates, respectively. The most common pathogens were Escherichia coli (33.4%), Klebsiella pneumoniae (10.8%), and Enterococcus faecium (10.7%). Pseudomonas aeruginosa and Acinetobacter baumannii were the most common non-Enterobacteriaceae Gram-negative pathogens. E. faecium, Enterococcus faecalis, and Staphylococcus aureus were the most common Gram-positive pathogens. E. coli, A. baumannii, and Enterobacter cloacae were more commonly found in ICU patients than in non-ICU patients. Overall, the antibiotics tested in the CARES exhibited diminished susceptibility to pathogens over the study period, especially extended spectrum β-lactamase producing isolates.ConclusionConsidering the current data set and high-level resistance of intra-abdominal pathogens to various antibiotics, further monitoring of the epidemiology of IAIs and their susceptibility to antibiotics through the CARES is warranted.

Clinical Characteristics and Risk Factors of Long-term Central Venous Catheter-associated Bloodstream Infections in Children.

Central line-associated bloodstream infections (CLABSIs) account for significant morbidity and mortality in patients with long-term central venous catheters (CVCs). This study was performed to identify the characteristics and risk factors of CLABSIs among children with long-term CVCs. A retrospective review of children who had a long-term CVC in Seoul National University Children's Hospital between 2011 and 2015 was performed. Data on patient demographics, the isolated pathogens and the status of CVC placement were collected. Clinical variables were compared between subjects with and without CLABSIs to determine the risk factors for CLABSIs. A total of 629 CVCs were inserted in 499 children during the 5-year period. The median age at insertion was 6.0 years (14 days-17.9 years), and hemato-oncologic disease was the most common underlying condition (n = 497, 79.0%). A total of 235 CLABSI episodes occurred in 155 children, with a rate of 0.93 per 1,000 catheter days. The most common pathogens were Klebsiella pneumoniae (n = 64, 27.2%), coagulase-negative staphylococci (n = 40, 17.0%) and Staphylococcus aureus (n = 28, 12.0%). In the univariate analysis, the gender, underlying disease, catheter characteristics and insertion technique did not increase the risk for CLABSI. In both the univariate and logistic regression analyses, patients with prior BSIs (odds ratio 1.66; 95% confidence interval: 1.090-2.531; P = 0.018) were more likely to have a CLABSI. CLABSI prevention is of particular concern for children with a prior BSI. Furthermore, the antimicrobial resistance of major pathogens should be monitored to enable the empiric selection of appropriate antibiotics in patients with long-term CVCs.

Targeting Imperfect Vaccines against Drug-Resistance Determinants: A Strategy for Countering the Rise of Drug Resistance

The growing prevalence of antimicrobial resistance in major pathogens is outpacing discovery of new antimicrobial classes. Vaccines mitigate the effect of antimicrobial resistance by reducing the need for treatment, but vaccines for many drug-resistant pathogens remain undiscovered or have limited efficacy, in part because some vaccines selectively favor pathogen strains that escape vaccine-induced immunity. A strain with even a modest advantage in vaccinated hosts can have high fitness in a population with high vaccine coverage, which can offset a strong selection pressure such as antimicrobial use that occurs in a small fraction of hosts. We propose a strategy to target vaccines against drug-resistant pathogens, by using resistance-conferring proteins as antigens in multicomponent vaccines. Resistance determinants may be weakly immunogenic, offering only modest specific protection against resistant strains. Therefore, we assess here how varying the specific efficacy of the vaccine against resistant strains would affect the proportion of drug-resistant vs. –sensitive strains population-wide for three pathogens – Streptococcus pneumoniae, Staphylococcus aureus, and influenza virus – in which drug resistance is a problem. Notably, if such vaccines confer even slightly higher protection (additional efficacy between 1% and 8%) against resistant variants than sensitive ones, they may be an effective tool in controlling the rise of resistant strains, given current levels of use for many antimicrobial agents. We show that the population-wide impact of such vaccines depends on the additional effect on resistant strains and on the overall effect (against all strains). Resistance-conferring accessory gene products or resistant alleles of essential genes could be valuable as components of vaccines even if their specific protective effect is weak.

SP29-3 Using time series analysis for surveillance of resistance and antimicrobial use. The ViResiST project

As antimicrobial resistance has been recognized as a big threat to public health, various surveillance systemsof antimicrobial resistance have been established at national and regional levels worldwide, although there is no global frameworkfor collaborative surveillance of antimicrobial resistance yet. Especially, antimicrobial resistance has been a serious public health threat in the Asian region, and it has become a global problembecause antimicrobial resistance can spread between countries or continents. Recent emergence and international spread of Escherichia coli that produce New Delhi Metallo-betalactamase-1 (NDM-1), from India to many countries worldwide, is one of the best examples of transmission of antimicrobial resistant pathogens, suggesting the importance of well-established surveillance system of antimicrobial resistance at international levels. In the Asian region, which comprises countries in different stages of economic development, the Asian Network of Surveillance of Resistant Pathogens (ANSORP) has been playing a key role in establishing an international surveillance network of antimicrobial resistance for the past 17 years. The ANSORP, which was organized in 1996, is an investigator-initiated, hospital-based, not-forprofit, non-governmental network for surveillance of antimicrobial resistance in major pathogens in the Asian region. The ANSORP has been operated by the Asia Pacific Foundation for Infectious Diseases (APFID), founded in 1999 to improve the global health through Asian initiatives by strengthening and coordinating national and international research-related activities on infectious diseases and antimicrobial resistance. The ANSORP has been expanded to the largest surveillance network in the Asian region, which includes over 120 hospitals in 14 countries (Korea, China, Hong Kong, Taiwan, Japan, the Philippines, Thailand, Vietnam, Indonesia, Malaysia, Singapore, India, Sri Lanka, and Saudi Arabia). The experts in the infectious diseases, pediatric infectious diseases, and clinical microbiology have collaborated and established a Local ANSORP Network in each country, collaborating with a ANSORP headquarter and a central reference laboratory in Seoul, Korea. The ANSORP has been conducting multinational surveillance studies for antimicrobial resistance of major human pathogens such as Streptococcus pneumoniae , Staphylococcus aureus , Enterococcus and Gram-negative bacilli, and infectious diseases including communityacquired pneumonia, hospital-acquired pneumonia, and pneumococcal diseases. The ANSORP has been trying to strengthen a surveillance network to get more reliable surveillance data and represent the current status of antimicrobial resistance in each country and the Asian region. In addition, the ANSORP has been collaborating with the Asia-Pacific Economic Cooperation (APEC) and the World Health Organization (WHO) to build future strategies to control and prevent antimicrobial resistance in the Asia Pacific region.

Antimicrobial resistance in major pathogens of hospital-acquired pneumonia in Asian countries

Antimicrobial resistance is a worldwide problem. For patients with hospital-acquired or ventilator-associated pneumonia, resistant pathogens pose a significant challenge to successful treatment outcomes and to the cost-effective delivery of health care. In the developing world, antibiotic resistance may be relatively more prevalent compared with Western countries. Common resistant pathogens include methicillin-resistant Staphylococcus aureus, multidrug resistant Pseudomonas aeruginosa, multidrug resistant Acinetobacter species, and extended-spectrum beta-lactamase-producing strains of Escherichia coli and Klebsiella pneumoniae. The emergence of these strains has provided a major impetus toward development of the present consensus treatment recommendations of the Asian HAP Working Group. The following review provides summary data regarding the incidence and prevalence of antibiotic-resistant pathogens in 10 Asian countries.

Epidemiology and clinical outcomes of community-acquired pneumonia in adult patients in Asian countries: a prospective study by the Asian network for surveillance of resistant pathogens

Appropriate antimicrobial treatment of community-acquired pneumonia (CAP) should be based on the distribution of aetiological pathogens, antimicrobial resistance of major pathogens, clinical characteristics and outcomes. We performed a prospective observational study of 955 cases of adult CAP in 14 hospitals in eight Asian countries. Microbiological evaluation to determine etiological pathogens as well as clinical evaluation was performed. Bronchopulmonary disease (29.9%) was the most frequent underlying disease, followed by cardiovascular diseases (19.9%), malignancy (11.7%) and neurological disorder (8.2%). Streptococcus pneumoniae (29.2%) was the most common isolate, followed by Klebsiella pneumoniae (15.4%) and Haemophilus influenzae (15.1%). Serological tests were positive for Mycoplasma pneumoniae (11.0%) and Chlamydia pneumoniae (13.4%). Only 1.1% was positive for Legionella pneumophila by urinary antigen test. Of the pneumococcal isolates, 56.1% were resistant to erythromycin and 52.6% were not susceptible to penicillin. Seventeen percent of CAP had mixed infection, especially S. pneumoniae with C. pneumoniae. The overall mortality rate was 7.3%, and nursing home residence, mechanical ventilation, malignancy, cardiovascular diseases, respiratory rate > 30/min and hyponatraemia were significant independent risk factors for mortality by multivariate analysis ( P < 0.05). The current data provide relevant information about pathogen distribution and antimicrobial resistance of major pathogens of CAP as well as clinical outcomes of illness in Asian countries.