Journal of Microbiology, Immunology and Infection

Combating antimicrobial resistance: Antimicrobial stewardship program in Taiwan

2012-04-06

Multi-drug-resistant organisms are increasingly recognized as a global public health issue. Healthcare-associated infection and antimicrobial resistance are also current challenges to the treatment of infectious diseases in Taiwan. Government health policies and the health care systems play a crucial role in determining the efficacy of interventions to contain antimicrobial resistance. National commitment to understand and address the problem is prerequisite. We analyzed and reviewed the antibiotic resistance related policies in Taiwan, USA, WHO and draft antimicrobial stewardship program to control effectively antibiotic resistance and spreading in Taiwan. Antimicrobial stewardship program in Taiwan includes establishment of national inter-sectoral antimicrobial stewardship task force, implementing antimicrobial-resistance management strategies, surveillance of HAI and antimicrobial resistance, conducting hospital infection control, enforcement of appropriate regulations and audit of antimicrobial use through hospital accreditation, inspection and national health insurance payment system. No action today, no cure tomorrow. Taiwan CDC would take a multifaceted, evidence-based approach and make every effort to combat antimicrobial resistance with stakeholders to limit the spread of multi-drug resistant strains and to reduce the generation of antibiotic resistant bacteria in Taiwan.

Patterns of sensitization to peanut allergen components in Taiwanese Preschool children

Yang-Te Lin, Chih-Te Charles Wu, Ju-Hui Cheng, Jing-Long Huang, Kuo-Wei Yeh — 2012-03-23

Background/Purpose: Peanut allergy is very common in Western countries, although it is seldom encountered in Eastern countries. Peanuts are comprised of at least 11 components, but the contribution to clinical symptoms by each component in each individual is not known. This study investigated the distributions of sensitivity to peanut allergen components among Taiwanese children who were sensitized to peanuts and followed the evolution of sensitization patterns to these components.Methods: We enrolled 29 preschool children (age=2.11±1.36 years) who were sensitized to peanuts above class 3. Serum was analyzed for specific immunoglobulin E (IgE) antibodies to recombinant Ara h 1, Ara h 2, Ara h 3, Ara h 8, and Ara h 9. Allergen component-specific IgE ≥0.35kUA/L was defined as positive. Eighteen children were retested 22.64±5.1 months later. Peanut allergy symptoms were recorded from detailed questionnaires.Results: The percentages of children sensitized to Ara h 1, 2, 3, 8, and 9 were, respectively, 51.8%, 65.5%, 62.1%, 13.8%, and 24.1%. Regarding changing patterns of peanut component sensitization at follow-up, children with clinical symptoms to peanuts had persistent elevations of Ara h 2-specific IgE: 12.6±1.01 up to 34.15±19.4kUA/L; p=0.144. In contrast, Ara h 2 concentrations decreased significantly in children without clinical symptoms. Ara h 8 and 9 were nonspecific for children with or without symptoms.Conclusion: Ara h 1, Ara h 2, and Ara h 3 were major components contributing to peanut sensitization in Taiwanese children. Ara h 2 was probably the most important component that contributed to clinical symptoms and remained steady in children who had peanut allergy.

Seroprevalence of enterovirus 71 and no evidence of crossprotection of enterovirus 71 antibody against the other enteroviruses in kindergarten children in Taipei city

2011-12-12

Background/Purpose: Enterovirus 71 (EV71) infection may cause severe neurological and cardiopulmonary complications, especially in preschool children. This study is to investigate the seroprevalence and seroconversion of EV71, and the crossprotection of EV71 antibody against other enteroviruses among kindergarteners.Methods: Overall 228 children in a public kindergarten were enrolled during two academic years, 2006 and 2007, in Taipei, Taiwan and we measured their EV71 neutralizing antibody. When the participants had herpangina; hand, foot and mouth disease (HFMD); febrile illness or respiratory symptoms, throat swabs were sampled and processed for viral culture and enterovirus real-time reverse transcriptase polymerase chain reaction (RT-PCR). Questionnaires, completed by the participants’ guardians, surveyed the history of allergy and annual incidence of symptoms related to enterovirus infection.Results: Seropositive rates of EV71 were 20% (32/163) in 2006 and 6% (4/65) in 2007. The rate of EV71 seropositivity increased with age (p < 0.01) in 2006 but it did not differ between genders (p = 0.14). No seroconversion was observed from 2006 to 2007. Herpangina occurred in 64% of children with EV71 seropositivity and 48% of those without EV71 antibodies (p = 0.12). Non-71 enterovirus infection, confirmed by viral study, occurred in 53% (19/36) of the EV71-seropositive children and in 53% (102/192) of EV71-seronegative children (p = 0.89). No participants had EV71 infection during the study period.Conclusion: EV71 did not frequently circulate in Taipei City from September 2006 to June 2008. Presence of EV71 neutralizing antibody was not associated with lower incidence of enterovirus infection caused by non-71 serotypes.

Diagnostic capacity of rapid influenza antigen test: Reappraisal with experience from the 2009 H1N1 pandemic

2011-12-19

Background: The rapid influenza antigen test (RIAT) has been questioned because of its poor sensitivity. Clinicians are confused as to what diagnostic help it may provide. RIAT was reappraised by other laboratory confirmatory tests for its diagnostic capacity.Methods: Records of RIAT, RT-PCR and virus culture, performed for upper respiratory tract samples during the period from July 2009 to January 2010, were reviewed. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of RIAT were evaluated with RT-PCR and virus culture as reference.Results: With either positive RT-PCR or positive virus culture as confirmation of presence of the virus, the overall sensitivity was 44.2% (235/532) and the overall PPV was 91.1% (235/258). With both negative RT-PCR and negative virus culture as confirmation of absence of the virus, the overall specificity was 98.2% (239/264) and the overall NPV was 92.6% (239/258). The PPV reached 96.2% during peak prevalence of infection and the NPV increased to 91.7% with low prevalence. The sensitivity for seasonal H3N2 was 56% (56/100), significantly better than the 39.6%, (156/394) for 2009 pandemic H1N1. Although RIAT positivity correlated to the viral load in samples, a substantial amount of negative RIAT samples had high viral load, with 16.8% (260/1548) of Ct value less than 36 and 8.8% (136/1548) of Ct value less than 31.Conclusion: An algorithm is derived for the fast and inexpensive point-of-care laboratory test RIAT for appropriate application in clinical diagnosis of influenza virus infection. In peak seasons, positive RIAT confirms the diagnosis, with PPV over 96%. In low seasons, negative RIAT sufficiently excludes the diagnosis, with NPV over 91%. The sensitivity of RIAT may vary with different species of the influenza virus. Negative RIAT is not necessarily equal to low viral load in the upper respiratory tract or low infectivity of the patient.

Amino acid substitutions of quinolone resistance determining regions in GyrA and ParC associated with quinolone resistance in Acinetobacter baumannii and Acinetobacter genomic species 13TU

2011-12-08

Background and purpose: Amino acid substitutions in GyrA and ParC are associated with resistance to quinolones in Acinetobacter baumannii (A baumannii), but this association is rarely elucidated in Acinetobacter genomic species (AGS) 13TU. This study aims to compare the association of amino acid substitutions in GyrA and ParC with quinolone resistance in A baumannii and AGS 13TU in Taiwan.Methods: Eleven representative strains of A baumannii and 13 strains of AGS 13TU were selected from 402 bacteremic isolates. The sequences of quinolone resistance determining regions of gyrA and parC were determined. Minimal inhibitory concentrations (MICs) of nalidixic acid, ciprofloxacin, levofloxacin and moxifloxacin were determined by agar dilution method.Results: Ser83Leu substitution in GyrA in A baumannii (one strain) was associated with resistance to all tested quinolones. This substitution plus a Ser80Leu or Ser80Tyr in ParC in A baumannii (four strains) and AGS 13TU (two strains) were associated with higher MICs of all quinolones. All but one quinolone MICs of A baumannii (one strain) and AGS 13TU (two strains) carrying a single substitution Ser56Asn in ParC remained in the susceptibility breakpoint. The Ser83Leu substitution in GyrA, even with additional Ser56Asn substitution in ParC, was associated with resistance to only nalidixic acid, but not other newer quinolones in AGS 13TU (two strains).Conclusion: A baumannii and AGS 13TU possessed similar quinolone resistance associated with amino acid substitutions in GyrA and ParC. Further study with more strains is needed to determine whether a single Ser83Leu substitution in GyrA was associated with a high level of quinolone MIC only in A baumannii, but not in AGS 13TU.

Outcomes and characteristics of ertapenem-nonsusceptible Klebsiella pneumoniae bacteremia at a university hospital in Northern Taiwan: A matched case-control study

2011-12-12

Background and purpose: Carbapenem-resistant Klebsiella pneumoniae is an emerging problem worldwide. The object of this study was to investigate the risk factors, characteristics and outcomes of ertapenem-nonsusceptible K pneumoniae (ENSKp) bacteremia.Methods: We conducted a 1:2 ratio matched case-control study. The controls were randomly selected among patients with ertapenem-susceptible K pneumoniae (ESKp) bacteremia and were matched with ENSKp cases for bacteremia.Results: Seventy-five patients were included in this study (25 cases and 50 controls). Bivariate analysis showed that prior exposure to either β-Lactam/β-Lactam-lactamase inhibitors (p = 0.008) or 4th generation cephalosporins (p < 0.001), chronic obstructive pulmonary disease (COPD) (p = 0.001), acute renal failure (p = 0.021), chronic kidney disease without dialysis (p = 0.021), recent hospital stay (p = 0.016), intensive care unit stay (p = 0.002), mechanical ventilation (p = 0.003), central venous catheter placement (p = 0.016), Foley indwelling (p = 0.022), polymicrobial bacteremia (p = 0.003) and higher Pittsburgh bacteremia score (p < 0.001) were associated with ENSKp bacteremia. The multivariate analysis showed that prior exposure to 4th generation cephalosporins (odds ratio [OR], 28.05; 95% confidence interval [CI], 2.92–269.85; p = 0.004), COPD (OR, 21.38; 95% CI, 2.95–154.92; p = 0.002) and higher Pittsburgh bacteremia score (OR, 1.35; 95% CI, 1.10–1.66; p = 0.004) were independent factors for ENSKp bacteremia. ENSKp bacteremia had a higher 14-day mortality rate than ESKp bacteremia (44.0% vs. 22.0%; p = 0.049). The overall in-hospital mortality rates for these two groups were 60.0% and 40.0% respectively (p = 0.102).Conclusion: ENSKp bacteremia had a poor outcome and the risk factors were prior exposure of 4th generation cephalosporins, COPD and higher Pittsburgh bacteremia score. Antibiotic stewardship may be the solution for the preventive strategy.

A multicenter surveillance of antimicrobial resistance on Stenotrophomonas maltophilia in Taiwan

2011-12-12

Background: Stenotrophomonas maltophilia has emerged as an important opportunistic pathogen in debilitated hosts. Clinical management of S. maltophilia is challenging due to its intrinsic resistance to a variety of antibiotics. This study investigated the trend and prevalence of antimicrobial resistance in S. maltophilia from a nationwide surveillance study in Taiwan.Methods: S. maltophilia isolates were collected biennially between 1998 and 2008 as part of the Taiwan Surveillance of Antimicrobial Resistance (TSAR) program from medical centers and regional hospitals throughout Taiwan. Minimal inhibitory concentrations (MIC) were determined using the Clinical and Laboratory Standards Institute reference broth microdilution method.Results: A total of 377 non-duplicate S. maltophilia isolates were collected from 38 hospitals. The majority of the isolates were from the respiratory tract (256, 67.9%), followed by blood (48, 12.7%). Overall, 376 (99.7%) isolates were susceptible to minocycline, 362 (96%) to tigecycline, 311 (82.5%) to trimethoprim/sulfamethoxazole (TMP-SMX), 300 (79.6%) to levofloxacin, 92 (24.4%) to ceftazidime, and 70 (18.6%) to ticarcillin-clavulanic acid. The MIC50/MIC90 of minocycline, tigecycline, TMP-SMX, levofloxacin, ceftazidime, and ticarcillin-clavulanic acid, were ≤0.5/1μg/mL, 0.25/1μg/mL, ≤0.25/8μg/mL, 1/4μg/mL, 32/128μg/mL, and 64/128μg/mL, respectively. A trend of increased non-susceptibility to levofloxacin (p=0.014) was observed over the 10-year study period. Compared to TMP-SMX-susceptible isolates, TMP-SMX-resistant isolates were less susceptible to levofloxacin (54.5% vs. 84.9%, p<0.001).Conclusion: In this 10-year study, minocycline and TMP-SMX remained the two antimicrobials with better in vitro activities against S. maltophilia than ceftazidime, levofloxacin, and ticarcillin-clavulanic acid. The activity of levofloxacin against S. maltophilia in Taiwan declined during the past 10 years.

Clinical characteristics of urosepsis caused by extended-spectrum beta-lactamase-producing Escherichia coli or Klebsiella pneumonia and their emergence in the community

2011-10-31

Background: The purpose of this study is to delineate clinical characteristics of urosepsis caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK) in different clinical settings, with an emphasis on community-acquired infections.Methods: A retrospective study was conducted at two medical centers in Taiwan. From May 2002 to August 2007, clinical data of adults with urosepsis caused by ESBL-EK were collected. Patients were categorized into three groups according to the place of acquisition. Baseline characteristics, microbiological data and clinical outcomes were compared.Results: Ninety-three cases of ESBL-EK urosepsis were included. Their mean age was 69.4 years, and 48.4% were men. Eleven (11.8%), 41 (44.1%), and 41 (44.1%) patients were categorized as having community-acquired, healthcare-associated, and hospital-acquired infections, respectively. Cases of ESBL-EK urosepsis from different settings shared similar characteristics in terms of age, gender, comorbidity and resistance profiles of bacterial strains. Of the bacterial isolates, 75% and 38.7% were resistant to fluoroquinolones and aminoglycosides, respectively. Cases of community-acquired urosepsis had a lower disease severity than those acquired in healthcare facilities or hospitals. Of note, there was no case fatality in 11 cases of community-acquired urosepsis and, in contrast, a crude mortality rate of 41.5% was found among adults with hospital-acquired urosepsis (p < 0.001).Conclusion: A limited number of adults with community-acquired urosepsis caused by ESBL-EK in the present study had a favorable outcome. Nonetheless, clinicians should be cautious of the emergence of urinary tract infections caused by ESBL-producers in the community setting.

Antimicrobial resistance of Moraxella catarrhalis isolates in Taiwan

2011-12-12

Background/Purpose: The prevalence of ampicillin-resistant Moraxella catarrhalis has been higher in Taiwan than in other countries, with reports of 97.7% in the 1990s. The aims of this study were to assess resistance trends for M. catarrhalis, which causes respiratory tract infections, against several classes of oral antibiotics and to compare the minimum inhibitory concentration (MIC) of antimicrobial agents against M. catarrhalis isolates between 1993–1994 and 2001–2004.Methods: Clinical isolates of M. catarrhalis (n = 314) were collected from 11 large medical centers in Taiwan between 2001 and 2004. β-Lactamase production tests were performed. The MICs for 13 different oral antibiotics were calculated using the agar dilution method. Pulsed-field gel electrophoresis (PFGE) was performed for 18 randomly selected high-level ampicillin-resistant (BRO-1 β-lactamase-positive, MIC ≥ 32 μg/mL) isolates to investigate their genetic relatedness.Results: The overall rate of β-lactamase-producing isolates was 97.8% (307/314). All isolates were susceptible to amoxicillin + clavulanate, chloramphenicol, cefixime, ciprofloxacin, erythromycin, levofloxacin, moxifloxacin, and roxithromycin. The rate of resistance to cefaclor and cefuroxime was 8.3% and 1.3%, respectively, while no resistance was found in 1993–1994. Resistance to trimethoprim–sulfamethoxazole (SXT) and tetracycline was 18.5% and 19.8%, respectively. Comparison of 1993–1994 and 2001–2004 isolates revealed that the zone diameter for amoxicillin + clavulanate disks decreased from 43 mm in 1993–1994 to 32 mm in 2001–2004 (p < 0.001). However, MIC50 (0.25 μg/mL in both 1993–1994 and 2001–2004) and MIC90 (0.5 μg/mL in both 1993–1994 and 2001–2004) for amoxicillin + clavulanate did not differ between the study periods. The PFGE typing results demonstrate that at least two closely related BRO-1 clones are spreading in Taiwan.Conclusion: The rates of resistance to cefaclor, cefuroxime, tetracycline and SXT are now increasing in Taiwan. Molecular typing showed that at least two closely related BRO-1 clones are circulating. Although amoxicillin + clavulanate remains the antimicrobial therapy of choice for M. catarrhalis infections, continued surveillance of antimicrobial susceptibility and application of control measures against further transmission are required to inhibit the emergence of the resistant strains.

Increasing opsonizing and killing effect of serum from patients with recurrent K1 Klebsiella pneumoniae liver abscess

2012-03-23

Background: Klebsiella pneumoniae liver abscess (KLA) is an emerging infectious disease caused by the virulent K pneumoniae strains of capsular serotype K1 and commonly associated with diabetes mellitus. Recurrent KLA is rarely reported and the mechanism of recurrence is uncertain. In this study we evaluated both phagocytosis by neutrophils and serum killing ability of serum from recurrent K1 KLA patients compared to normal healthy subjects (NHS).Methods: This prospective study included six cases of recurrent K1 KLA consisting of three male and three female patients with a mean age of 67.2 years (range, 56-88 years). The different serotypes of K pneumoniae were reacted with serum from patients with recurrent KLA and NHS. Subsequent phagocytosis by neutrophils was determined using flow cytometry and serum killing assays were performed.Results: The most common underlying disease in patients with recurrent KLA was diabetes mellitus, occurring in about 83.3% (5/6) of patients. The antibiogram of the strains associated with recurrent KLA remained uniquely resistant to ampicillin. The average percentage derived from the serum killing assays showed serotype K1 and K2 resistance to serum from NHS (1281% and 621%, respectively); however, serum susceptibly was observed in the serum of patients with recurrent K1 KLA (0.3% and 1.1%, respectively). A significant increase in neutrophil phagocytosis of serotype K1 was observed following opsonisation with serum from patients with recurrent KLA compared with serum from NHS (p = 0.008). No significant difference in the phagocytic rate of non-K1/K2 or K2 serotypes was observed between NHS and patients with recurrent KLA (p = 0.76 and p = 0.132, respectively).Conclusion: These preliminary results showed possible immunologic protection in patients with recurrent KLA due to increasing opsonization and serum killing.

Lethal toxic encephalopathy due to childhood shigellosis or Ekiri syndrome

2011-12-16

Lethal toxic encephalopathy due to shigellosis or Ekiri syndrome is a rare complication of shigellosis with a high fatality rate. Data are very limited on factors that can predict this encephalopathy, so we evaluated clinical and laboratory characteristics for these patients. In this study children with extreme toxicity and convulsions followed by rapid neurological deterioration resulting in brain edema and fatal outcome without sepsis and severe dehydration were selected as having lethal toxic encephalopathy. There were 1295 children with shigellosis during the 10 years of the study. Five children (0.4%) had lethal toxic encephalopathy due to shigellosis. Death occurred following rapid neurological detoriation resulting in brain edema despite intensive treatment. Evidence of brain edema may be a prediction factor for death. Early recognition of encephalopathy and measures to prevent brain edema may improve patient outcome.

Shewanella putrefaciens, a rare cause of splenic abscess

Norwani Basir, Alice Moi Ling Yong, Vui Heng Chong — 2011-12-12

Splenic abscess is uncommon and is still associated with significant morbidity and mortality. Gram-negative bacilli are the most commonly isolated organisms, followed by Gram-positive cocci. However, the predominant organisms found depend on the geographic location. Shewanella putrefaciens is a Gram-negative non-fermentative oxidative bacillus found in the environment. Infection usually manifests with a number of clinical syndromes, most commonly as skin or soft tissue infections, typically in patients whose immune system is compromised. Intra-abdominal abscess is extremely rare. We report a case of a 22-year-old female who presented with S. putrefaciens splenic abscesses as the first manifestation of diabetes mellitus, which was successfully managed with a course of antibiotic therapy.

Fulminant Aeromonas hydrophila infection during acute lymphoblastic leukemia treatment

2012-01-24

Aeromonas hydrophila septicemia has a fulminant course and it has been usually reported in immunocompromised hosts and rarely among children with leukemia. High morbidity and mortality is associated with A hydrophila infections. We describe the case of a child with acute lymphoblastic leukemia who presented with septicemia due to A hydrophila. The patient presented with fever and skin discoloration during a febrile neutropenia episode, which rapidly evolved into bacteremia and extensive thigh suppuration, fasciitis, and myonecrosis. Apart from antibiotic treatment, surgical debridement to relieve compartment pressure and prevent further lower extremity compromise was promptly performed. Despite long delays in chemotherapy and an extensive tissue gap, primary closure of the involved area was possible with full cosmetic and functional limb recovery, and the patient has remained in clinical remission for more than 7 years.

Successful treatment of Aerococcus viridans endocarditis in a patient allergic to penicillin

2011-12-12

Aerococcus viridans is a rare human pathogen that occasionally causes endocarditis. Most of the reported cases of endocarditis have been treated with penicillin. Here we describe a patient who was allergic to penicillin and was successfully treated with cefotaxime.

Distribution of Candida species causing bloodstream infections

Chih-Cheng Lai, Shiow-Jen Gau, Che-Kim Tan — 2012-03-23

Recently, Chi et al compared the risk factors and outcomes of bloodstream infections due to Candida albicans with those due to non-albicans species at a hospital in northern Taiwan in the August 2011 issue of the Journal of Microbiology, Immunology, and Infection. In that study, the authors retrospectively enrolled 108 patients with candidemia during the period October 2007 to July 2009. Of those patients, 61 (56.5%) had C. albicans bloodstream infections and 47 (43.5%) had non-albicans candidemia. The species distributions were as follows: C. glabrata (n = 19, 17.6%), C. tropicalis (n = 14, 13.0%), C. krusei (n = 1, 1%), and C. haemonulonii (n = 1, 1%). Although these findings are interesting, we wondered whether they could be generalized to other parts of Taiwan. Therefore, we performed this study to investigate the species distribution of Candida isolates causing fungemia in southern Taiwan.

Improved outcome of Pneumocystis pneumonia by early treatment

2012-03-19

In the August 2011 issue, Wang et al conducted a retrospective study to identify predictors of mortality and to derive a Pneumocystis jirovecii pneumonia (PJP) mortality prediction rule. This study determined that three predictors, hypotension (systolic pressure 110 mmHg), hypoxemia (PaO2 at room air 60 mmHg), and lymphopenia (lymphocytes 10%), were associated with mortality and stratified the patients into three groups with increasing risks for mortality, and therefore may assist the clinicians to take accurate strategies for better care and outcomes of human immunodeficiency virus (HIV)-infected patients with PJP. Many of these predictors were similar to those found in other cohorts. It is often difficult to compare between studies, because they were usually performed in different periods and at individual centers that may have varying levels of expertise in HIV care and diverse patient populations. The consistency of these findings suggests that perhaps primary physicians have reached a threshold in the care of HIV-infected patients with PJP and that further improvements will require discovery of new therapies or changes in other aspects of care.