Shio Shin Jean

High burden of antimicrobial resistance in Asia

Antimicrobial resistance is associated with high mortality rates and high medical costs. Marked variations in the resistance profiles of bacterial and fungal pathogens as well as the quality of public hygiene have had a considerable impact on the effectiveness of antimicrobial agents in Asian countries. In Asia, one of the epicentres of antimicrobial drug resistance, there is an alarming number of antibiotic-resistant species, including penicillin- and erythromycin-resistant Streptococcus pneumoniae, ampicillin-resistant Haemophilus influenzae, multidrug-resistant (MDR) Acinetobacter baumannii, extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae (particularly mediated by CTX-M-9, CTX-M-14 and CTX-M-15), New Delhi metallo-β-lactamase 1 (NDM-1)-producing Enterobacteriaceae, MDR Salmonella enterica serotypes Choleraesuis and Typhi, carbapenem-resistant A. baumannii (OXA-58 and OXA-23 carbapenemases) and azole-resistant Candida glabrata. A few clones of MDR A. baumannii and hospital-acquired meticillin-resistant Staphylococcus aureus (MRSA) have been widely disseminated in hospital settings in Asia, and K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains have been widely distributed in China. In addition, the emergence of extensively drug-resistant Mycobacterium tuberculosis (XDR-TB) has illustrated the need for regular monitoring of resistance profiles of clinical isolates as well as the deliberative use of fluoroquinolones. Continuous surveillance of resistance data from clinical isolates as well as implementation of strict infection control policies in healthcare settings are required to mitigate the progression of antimicrobial resistance.

Nationwide surveillance of antimicrobial resistance among non-fermentative Gram-negative bacteria in Intensive Care Units in Taiwan: SMART programme data 2005.

A nationwide surveillance of the antimicrobial susceptibilities of glucose non-fermentative Gram-negative bacteria isolates was conducted from 1 September 2005 to 30 November 2005 in Taiwan. A total of 456 isolates were recovered from patients hospitalised in the Intensive Care Units (ICUs) of ten major teaching hospitals. Rates of resistant pathogens, such as ciprofloxacin-resistant Pseudomonas aeruginosa (19%) and imipenem-resistant Acinetobacter baumannii (25%), were higher than those reported in 2000 (8% and 22%, respectively). Increased rates of isolates with resistant phenotypes correlated with prolonged length of ICU stay (48h to <or=7 days vs. >7 days) for ceftazidime-non-susceptible P. aeruginosa (20.0% and 29.7%, respectively), imipenem-non-susceptible P. aeruginosa (4.0% and 13.5%, respectively) and imipenem-non-susceptible A. baumannii (15.4% and 29.8%, respectively), but not for ciprofloxacin-resistant P. aeruginosa. Alarming rates of emergence of extensively drug-resistant (XDR) A. baumannii (15%) and XDR P. aeruginosa (1.8%) were found, particularly among those isolates that were not susceptible to tigecycline and colistin. Interhospital dissemination of some clones of XDR A. baumannii in different ICUs was also noted. This study illustrates the crucial nature of continuous nationwide surveillance of resistant pathogens and implementation of effective strategies for ICU infection control and antibiotic restriction.

Bacteremic Streptococcus bovis infections at a university hospital, 1992-2001.

BACKGROUND AND PURPOSE The association of Streptococcus bovis biotypes with types of clinical infection and underlying malignancies has rarely been reported in Taiwan. The aim of this study was to characterize the clinical features and microbiological characteristics of patients with S. bovis bacteremia. METHODS From January 1992 to December 2001, 62 patients with S. bovis bacteremia were treated at National Taiwan University Hospital. Their demographic characteristics, clinical features, results of imaging studies, pathological findings, and laboratory data were retrospectively analyzed. Antimicrobial susceptibilities were determined using the agar dilution method and biotypes were determined using the API 20 Strep system. RESULTS The majority of cases (76%) occurred during the 1996-1997 and 1999-2000 periods. Thirty five patients were male, and the mean age of the 62 patients was 61 years. Underlying diseases included malignancies (40%), cardiac diseases (27%), diabetes mellitus (24%), and liver cirrhosis (21%). Fifty two percent (n = 32) of patients presented with primary bacteremia and 24% (15) with definite or possible infective endocarditis. Thirteen percent (8) presented with hepatobiliary infections (acute cholecystitis and biliary tract infection). Ten patients (16%) had polymicrobial bacteremia. All of the concomitant pathogen(s) were Gram-negative rods, among which Escherichia coli predominated. The mortality rate on day 30 of illness was 21%. High Acute Physiology and Chronic Health Evaluation (APACHE) II score on the day of positive blood culture was associated with high mortality. Among the 19 patients (31%) who underwent colonoscopy, 9 (47%) had colonic lesions (tubular adenomas or carcinomas). Of the 26 patients (41%) who underwent echocardiography, 14 (54%) had vegetation in the valves. Of the 47 S. bovis isolates examined for biotypes, 37 (79%) were biotype II (29 of biotype II/2 and 8 of biotype II/1) and 10 (21%) were biotype I. The majority of isolates causing primary bacteremia (92%), hepatobiliary infections (100%) and primary bacterial peritonitis (100%) were biotype II, while 67% of isolates associated with infective endocarditis were biotype I. All isolates were susceptible to penicillin. CONCLUSIONS Infective endocarditis should be highly suspected in patients with bacteremia due to S. bovis biotype I. Investigations for intra-abdominal foci other than the colon should be undertaken in patients with bacteremia caused by S. bovis biotype II. Due to the increasing number of S. bovis bacteremia patients at the hospital and unknown origins of about 50% of bacteremia cases, the need for colonoscopy and echocardiography in each case and biotyping of each blood isolate should be emphasized.

Current review of antimicrobial treatment of nosocomial pneumonia caused by multidrug-resistant pathogens

Nosocomial pneumonia (including ventilator-associated pneumonia; VAP), a consistently difficult-to-treat entity, is frequently caused by multidrug-resistant (MDR) or pandrug-resistant (PDR) bacteria. Given the high mortality rates caused by drug-resistant bacteria and the difficulty of developing new potent antibiotics to target the problematic pathogens, combination regimens are under ardent evaluation as new strategies to overcome increasing drug resistance. Adjustment of the administration method of certain β-lactams (meropenem, or imipenem/cilastatin), or combination of tigecycline with some agents, may show promise with regard to successful management of MDR or PDR Acinetobacter baumannii pneumonia. Additionally, vancomycin plus rifampicin is an effective regimen against nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) responding poorly to vancomycin monotherapy. The clinical appropriateness of parenteral colistin against pneumonia caused by MDR A. baumannii has been established in a clinical trial. Facing the decline of clinical vancomycin efficacy after initial use, linezolid might be the drug of choice with regard to the treatment of MRSA-VAP. The role of tigecycline monotherapy for the management of nosocomial pneumonia caused by MRSA and extended-spectrum β-lactamase-producing Enterobacteriaceae needs to be cautiously evaluated.

Epidemiology and antimicrobial susceptibility profiles of pathogens causing urinary tract infections in the Asia-Pacific region: Results from the Study for Monitoring Antimicrobial Resistance Trends (SMART), 2010–2013

A total of 9599 isolates of Gram-negative bacteria (GNB) causing urinary tract infections (UTIs) were collected from 60 centres in 13 countries in the Asia-Pacific region from 2010-2013. These isolates comprised Enterobacteriaceae species (mainly Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Klebsiella oxytoca, Enterobacter cloacae and Morganella morganii) and non-fermentative GNB species (predominantly Pseudomonas aeruginosa and Acinetobacter baumannii). In vitro susceptibilities were determined by the agar dilution method and susceptibility profiles were determined using the minimum inhibitory concentration (MIC) interpretive breakpoints recommended by the Clinical and Laboratory Standards Institute in 2015. Production of extended-spectrum β-lactamases (ESBLs) amongst E. coli, K. pneumoniae, P. mirabilis and K. oxytoca isolates was determined by the double-disk synergy test. China, Vietnam, India, Thailand and the Philippines had the highest rates of GNB species producing ESBLs and the highest rates of cephalosporin resistance. ESBL production and hospital-acquired infection (isolates obtained ≥48 h after admission) significantly compromised the susceptibility of isolates of E. coli and K. pneumoniae to ciprofloxacin, levofloxacin and most β-lactams, with the exception of imipenem and ertapenem. However, >87% of ESBL-producing E. coli strains were susceptible to amikacin and piperacillin/tazobactam, indicating that these antibiotics might be appropriate alternatives for treating UTIs due to ESBL-producing E. coli. Fluoroquinolones were shown to be inappropriate as empirical therapy for UTIs. Antibiotic resistance is a serious problem in the Asia-Pacific region. Therefore, continuous monitoring of evolutionary trends in the susceptibility profiles of GNB causing UTIs in Asia is crucial.

Antimicrobial Drug Resistance in Taiwan

Antimicrobial resistance is a major global health threat associated with high mortality rates and high medical costs. Geographic variations in resistance profiles of bacterial and fungal pathogens have had a considerable impact on antimicrobial prescription. In Taiwan, there is an alarmingly high prevalence of penicillin-resistant Streptococcus pneumoniae, multidrug-resistant and extensively drug-resistant (XDR) Pseudomonas aeruginosa and Acinetobacter baumannii, extended-spectrum β-lactamase-producing Klebsiella pneumoniae, penicillin- and fluoroquinolone-resistant Neisseria gonorrhoeae, and azole-resistant Candida species. In addition, the emergence of XDR Mycobacterium tuberculosis has illustrated the need for regular monitoring of the resistance profiles of clinical isolates. A few clones of XDR A. baumannii and methicillin-resistant Staphylococcus aureus of unique sequence type (ST 59) have disseminated in Taiwanese hospital settings. Besides, the existence of a transposon-harboring carbapenemase gene has been verified in XDR P aeruginosa strains throughout Taiwan. An end to the worsening trends in the emergence of antimicrobial resistance will require continuous survey of resistance data from clinical isolates and effective implementation of strict infection control policies in healthcare settings and animal husbandry.

Nationwide surveillance of antimicrobial resistance among Enterobacteriaceae in intensive care units in Taiwan

To determine the antimicrobial resistance profiles among clinical isolates of Enterobacteriaceae in Taiwanese intensive care units (ICUs), a national surveillance of antibiotic resistance among important Enterobacteriaceae was conducted from September 2005 through November 2005 at the ICUs of ten major teaching hospitals in Taiwan. A total of 574 Enterobacteriaceae isolates recovered from various clinical samples of our ICU patients were submitted for in vitro test. Minimum inhibitory concentrations (MICs) of these isolates to 18 antimicrobial agents were determined by the broth microdilution method. The prevalences of Enterobacteriaceae isolates with phenotypic extended-spectrum β-lactamase (ESBL) production were 26% in Klebsiella pneumoniae, 16% in Serratia marcescens, 14% in Escherichia coli, and 13% in Proteus mirabilis, in which a significantly rising prevalence of ESBL production among K. pneumoniae was noted (p = 0.002) when compared with a previous Taiwanese survey in 2000. Heterogeneous resistance to various fluoroquinolones was found among our Enterobacteriaceae isolates, except for Entetrobacter cloacae. Emergence of ertapenem-resistant isolates of E. coli, K. pneumoniae, E. cloacae, and S. marcescens was noted. Gradually increasing rates of drug-resistant Enterobacteriaceae were noted in Taiwanese ICUs. Periodic surveillance of the evolutionary trend of antimicrobial resistance among ICU isolates is crucial for starting appropriately empirical antimicrobial therapy in the future.

Carbapenemase-producing Gram-negative bacteria: current epidemics, antimicrobial susceptibility and treatment options

Carbapenemases, with versatile hydrolytic capacity against β-lactams, are now an important cause of resistance of Gram-negative bacteria. The genes encoding for the acquired carbapenemases are associated with a high potential for dissemination. In addition, infections due to Gram-negative bacteria with acquired carbapenemase production would lead to high clinical mortality rates. Of the acquired carbapenemases, Klebsiella pneumoniae carbapenemase (Ambler class A), Verona integron-encoded metallo-β-lactamase (Ambler class B), New Delhi metallo-β-lactamase (Ambler class B) and many OXA enzymes (OXA-23-like, OXA-24-like, OXA-48-like, OXA-58-like, class D) are considered to be responsible for the worldwide resistance epidemics. As compared with monotherapy with colistin or tigecycline, combination therapy has been shown to effectively lower case-fatality rates. However, development of new antibiotics is crucial in the present pandrug-resistant era.

Nationwide spread of Klebsiella pneumoniae carbapenemase-2-producing K. pneumoniae sequence type 11 in Taiwan

Department of Emergency Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, ROC Division of Infectious Diseases, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, ROC Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan, ROC Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, ROC

Acute generalized exanthematous pustulosis due to teicoplanin.

Acute generalized exanthematous pustulosis (AGEP) is characterized by the sudden onset of fever, numerous nonfollicular small superficial sterile pustules on an erythematous background and rapid spontaneous healing within 15 days [1, 2]. In most cases, the causative agent is a drug, mainly ß-lactam and macrolide antimicrobials [3]. The other causative factors include viral infections and hypersensitivity to mercury [1, 2]. There is an increasing list of other drugs that can lead to AGEP [1]. We herein report a case of teicoplanininduced AGEP, which has not been described in the literature based on searching the Medline database. A 66-year-old man without a personal or family history of psoriasis received a coronary artery bypass graft due to his three-vessel coronary artery disease. He also had a long history of diabetes mellitus. Low-grade fever, persistent hyperglycemia, leukocytosis up to 22,810/Ìl and pus discharge from the sternotomy wound were noted 2 weeks after the operation. The pus culture revealed methicillinresistant Staphylococcus epidermidis. Therefore, vancomycin was administered for 16 days, followed by a combination with gentamicin for 4 additional days due to persistent low-grade fever (38.8°C). One week later, the leukocytosis normalized and the repeated wound culture result was negative. Under the suspicion of vancomycininduced drug fever and poor renal function of the patient, the antibiotic therapy was changed to teicoplanin (300 mg intravenous infusion as the loading dose, followed by 400 mg every other day as the maintenance dose). However, 3 days later, severe pruritus and numerous tiny pustules on an erythematous base over the trunk and limbs developed after giving the second injection of teicoplanin (fig. 1). Persistent fever (138.3°C) with leukocytosis (14,930/Ìl) was also noted. The concurrent medications included insulin, digoxin, furosemide, enalapril, nifedipine, magnesium oxide and sucralfate. All of them had been administered for more than 1 month and were continued during and after the episode of skin eruption. The histopathological study of the skin lesion revealed a picture compatible with AGEP (fig. 2). The biopsy tissue cultures for bacteria and fungi were all negative. After the second injection of teicoplanin, the patient did not receive any antibiotic therapy, and the skin lesions resolved spontaneously 7 days later with normalization of the blood leukocyte count and resolution of fever. Patch tests using 6.67, 0.667 and 0.2% (the therapeutic concentration) of teicoplanin with or without tape stripping as well as therapeutic concentrations of vancomycin and gentamicin (0.5 and 0.8%, respectively) in normal saline were performed 1 month later. All of them were read 3 days later and showed negative results. Teicoplanin is well known for its lower nephrotoxicity and ototoxicity as well as its fewer adverse cutaneous effects than vancomycin [4]. The clinical and pathological features of the patient are consistent with the diagnostic criteria for AGEP [1, 2]. Although the Fig. 1. Numerous small, nonfollicular pustules on an erythematous base on the right thigh.