Yeu-Jun Lau

A multicenter study of risk factors and outcome of hospitalized patients with infections due to carbapenem-resistant Acinetobacter baumannii

BACKGROUND Risk factors and outcome in patients who acquire nosocomial infections due to carbapenem-resistant Acinetobacter baumannii (CRAB) are rarely investigated. METHODS A multicenter retrospective study was conducted to analyze the clinical and microbiological data of patients with nosocomial infections due to A. baumannii in 10 hospitals around Taiwan from May 2004 to December 2006. Comparisons were made between patients with infections due to CRAB and patients with infections due to carbapenem-susceptible A. baumannii (CSAB). RESULTS One hundred and twenty-one patients carrying CRAB (infections, n=91) and 127 patients carrying CSAB (infections, n=97) were recruited for analysis. Compared with patients with CSAB infections, patients with CRAB infections had a longer duration of hospital stay before A. baumannii was isolated (median 48 vs. 21 days, p<0.001) and were more likely to have had exposure to a carbapenem (adjusted odds ratio (AOR) 2.57, 95% confidence interval (95% CI) 1.43-5.35; p=0.02) and an intensive care unit (ICU) stay (AOR 3.42, 95% CI 1.76-5.26; p=0.008). Risk factors associated with CRAB bacteremia included duration of hospital stay before onset of bacteremia (AOR 1.009 per 1-day longer, 95% CI 1.03-1.24; p=0.049), prior colonization with A. baumannii (AOR 3.27, 95% CI 1.99-5.93; p=0.002), and hospitalization in the ICU (AOR 6.12, 95% CI 1.58-13.68; p=0.009). Patients with CRAB bacteremia had a higher mortality rate than patients with CSAB bacteremia (46.0% vs. 28.3%, p=0.04). Multivariate analysis showed that carbapenem resistance (AOR 5.31, 95% CI 1.88-13.25; p=0.002), central venous catheterization (AOR 3.27, 95% CI 1.55-10.56; p=0.009), and ICU stay (AOR 2.56, 95% CI 1.15-8.85; p=0.04) were independent variables associated with mortality in patients with A. baumannii bacteremia. CONCLUSIONS Patients with CRAB infections have a higher mortality rate than those with CSAB infections. Longer hospital stay, colonization with A. baumannii, and admission to the ICU were associated with the development of CRAB bacteremia.

Fusidic acid for the treatment of bone and joint infections caused by meticillin-resistant Staphylococcus aureus

There is a lack of surveillance data on resistance to fusidic acid (FA) in Asia, and no reviews of FA usage for the treatment of orthopaedic infections have been conducted since the year 2000. In this study, we present a systemic literature review of FA resistance in Asia and the clinical use of FA for the treatment of bone and joint infections (BJIs). The in vitro activity of FA against meticillin-resistant Staphylococcus aureus (MRSA) isolates remains good, with low (<10%) resistance rates in most Asian countries. FA in Asia appears to be a better oral anti-MRSA agent than trimethoprim/sulfamethoxazole and clindamycin. More than 80 cases of FA use for BJI have been reported since 2000 and the recurrence or failure rate is <10%. There is much evidence supporting the use of FA in combination with other antibiotics (e.g. rifampicin) as an oral treatment following intravenous glycopeptide treatment for BJIs.

Antimicrobial susceptibility of clinical isolates of Acinetobacter baumannii

The in-vitro activity of 18 antimicrobial agents alone or in combination against 248 clinical isolates of Acinetobacter baumannii from Taiwan were tested by agar dilution. The MIC90S of ampicillin, amoxicillin, piperacillin, cefuroxime, cefotaxime, ceftriaxone, gentamicin, and amikacin were at least 128 mu g/ml. Ceftazidime, cefepime, sulbactam, clavulanic acid, and tazobactam presented moderate activity with MIC90S of 32, 16, 16, 32, and 32 mu g/ml, respectively. The increased activity of ampicillin/sulbactam, amoxicillin/clavulanic acid, and piperacillin/tazobactam was due to the intrinsic effect of sulbactam, clavulanic acid, and tazobactam, respectively. Imipenem, meropenem, and ciprofloxacin were the most active antimicrobial agents with MIC90S of 1, 1, and 0.5 mu g/ml, respectively. Nineteen isolates (7.7%) were resistant to all aminoglycosides and beta-lactam antibiotics, except carbapenems and ciprofloxacin. We are concerned about the multidrug resistance of A. baumannii in this study.

Does empirical treatment of community-acquired pneumonia with fluoroquinolones delay tuberculosis treatment and result in fluoroquinolone resistance in Mycobacterium tuberculosis? Controversies and solutions.

Abstract The role of fluoroquinolones (FQs) as empirical therapy for community-acquired pneumonia (CAP) remains controversial in countries with high tuberculosis (TB) endemicity owing to the possibility of delayed TB diagnosis and treatment and the emergence of FQ resistance in Mycobacterium tuberculosis. Although the rates of macrolide-resistant Streptococcus pneumoniae and amoxicillin/clavulanic acid-resistant Haemophilus influenzae have risen to alarming levels, the rates of respiratory FQ (RFQ) resistance amongst these isolates remain relatively low. It is reported that ca. 1–7% of CAP cases are re-diagnosed as pulmonary TB in Asian countries. A longer duration (≥7 days) of symptoms, a history of night sweats, lack of fever (>38°C), infection involving the upper lobe, presence of cavitary infiltrates, opacity in the lower lung without the presence of air, low total white blood cell count and the presence of lymphopenia are predictive of pulmonary TB. Amongst patients with CAP who reside in TB-endemic countries who are suspected of having TB, imaging studies as well as aggressive microbiological investigations need to be performed early on. Previous exposure to a FQ for >10 days in patients with TB is associated with the emergence of FQ-resistant M. tuberculosis isolates. However, rates of M. tuberculosis isolates with FQ resistance are significantly higher amongst multidrug-resistant M. tuberculosis isolates than amongst susceptible isolates. Consequently, in Taiwan and also in other countries with TB endemicity, a short-course (5-day) regimen of a RFQ is still recommended for empirical therapy for CAP patients if the patient is at low risk for TB.

Comparison of susceptibility to extended-spectrum β-lactam antibiotics and ciprofloxacin among gram-negative bacilli isolated from intensive care units

The in vitro activities of extended-spectrum beta-lactam antibiotics (including piperacillin, cefotaxime, ceftriaxone, ceftazidime, cefepime, imipenem, and meropenems) were assessed and compared with the activity of ciprofloxacin against 366 clinical Gram-negative bacilli isolates from the intensive care units of Taichung Veterans General Hospital. The most prevalent species isolated were Pseudomonas aeruginosa and Acinetobacter baumannii. The activities of ceftazidime, cefepime, imipenem, and meropenem against these isolates were comparable to that of ciprofloxacin. Meropenem was found to be the most potent extended-spectrum beta-lactam antibiotic tested and the MIC50s and MIC90s for most of these multiresistant strains were lower than those of imipenem, ceftazidime, and cefepime, except for Stenotrophomonas maltophilia. The extended-spectrum beta-lactam antibiotics that were still active against S. maltophilia were piperacillin and ceftazidime. More than 50% of Enterobacter spp. were resistant to third-generation cephalosporins and piperacillin, but they remained susceptible to carbapenems and cefepime.

Comparison of polymerase chain reaction and pulsed-field gel electrophoresis for the epidemiological typing of Campylobacter jejuni

Seventeen sporadic Campylobacter jejuni enteritis cases occurred in Taichung City, Taiwan between July 1995 and September 1995. Pulsed-field gel electrophoresis (PFGE) and enterobacterial repetitive intergenic consensus (ERIC-1) primed polymerase chain reaction (PCR) techniques were compared for the epidemiological typing of the 17 C. jejuni isolates. Fourteen distinct PFGE fingerprint patterns were observed. Fifteen distinct PCR fingerprint patterns were demonstrated. Two clusters of isolates (isolates 5 and 6; isolates 10, 11 respectively) were found to be genetically indistinguishable by both methods. In conclusion, we consider that PFGE is a highly reproducible method for determining the relatedness among the C. jejuni isolates in this study, although their limited numbers of restriction fragments may reduce the discriminatory power. Although less reproducible than PFGE typing, ERIC-1 primed PCR can be used as a simple and rapid tool to discriminate different strains of C. jejuni.

Comparison of polymerase chain reaction and pulsed-field gel electrophoresis for the epidemiological typing of Alcaligenes xylosoxidans subsp. xylosoxidans in a burn unit.

Eighteen isolates of Alcaligenes xylosoxidans subsp. xylosoxidans were collected from clinical specimens of 15 patients in a burn unit and a plastic surgery ward over a 16-month period. Pulsed-field gel electrophoresis and polymerase chain reaction (PCR) were compared for the epidemiologic typing of these 18 isolates and fifteen epidemiologically unrelated strains. These 18 isolates demonstrated an identical fingerprint pattern and were easily distinguished from the 15 epidemiologically unrelated strains by pulsed-field gel electrophoresis typing and both enterobacterial repetitive intergenic concensus and repetitive extragenic palindrome-primed PCR fingerprinting. We conclude that pulsed-field gel electrophoresis analysis of XbaI-digested genomic DNA is a highly discriminatory and reproducible method for epidemiological typing of A. xylosoxidans subsp. xylosoxidans isolates. However, poor resolution due to frequent cutting in the smaller fragments (< 145.5 Kb) may lead to difficulty in interpretation. PCR is a rapid and highly discriminatory, but less reproducible, technique with occasional loss of major bands. The fingerprints produced by repetitive extragenic palindrome primed PCR had more intense bands and were easier to read than those produced by enterobacterial repetitive intergenic concensus-primed PCR in this study.

Multicenter surveillance of antimicrobial resistance of Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis to 14 oral antibiotics.

BACKGROUND AND PURPOSE Data on the in vitro activities of orally administered cephalosporins, particularly third-generation cephalosporins, against recent pathogens responsible for community-respiratory tract infection are lacking. METHODS A susceptibility surveillance of 267 isolates of Streptococcus pneumoniae, 205 of Streptococcus pyogenes, 204 of Haemophilus influenzae, and 147 of Moraxella catarrhalis to 14 oral antimicrobial agents using the agar dilution method was carried out from March 2002 to October 2002 in Taiwan. RESULTS High rates of non-susceptibility to penicillin (60%), cefaclor (67%), cefuroxime (62%), cefpodoxime (64%), clarithromycin (91%), and trimethoprim-sulfamethoxazole (98%) for S. pneumoniae isolates and high rates of non-susceptibility to ampicillin (70%), clarithromycin (34%), and trimethoprim-sulfamethoxazole (63%) for H. influenzae isolates were found. The rank order of oral cephalosporin activity based on the minimum concentrations at which 90% of the isolates were inhibited (MIC90s) for S. pneumoniae was cefpodoxime > cefuroxime > cefixime > cefaclor, cephradine > cephalexin and for H. influenzae and M. catarrhalis was cefixime > cefpodoxime > cefuroxime > cefaclor > cephalexin, cephradine. Among the 75 S. pneumoniae isolates resistant to penicillin (MICs ranged 2 to 4 mg/L), 4% were intermediate to amoxicillin and > 90% were resistant to cefaclor, cefuroxime, and cefpodoxime. For S. pyogenes isolates, all were susceptible to penicillin, 21% were not susceptible to clarithromycin and 4% were not susceptible to clindamycin. Thirty four percent of H. influenzae isolates were not susceptible to clarithromycin. The MIC90 of clarithromycin against M. catarrhalis isolates was 0.5 mg/L. CONCLUSIONS Cefpodoxime, cefixime, and cefuroxime are promising agents against these bacterial pathogens, except for penicillin-non-susceptible S. pneumoniae isolates.

Epidemiology and staphylococcal cassette chromosome mec typing of methicillin- resistant Staphylococcus aureus isolates in Taiwan: A multicenter study

BACKGROUND/PURPOSE After community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) was identified, new community-onset, healthcare-associated MRSA (HA-MRSA-CO) infections have been noticed as MRSA infection in patients with community-onset infection who have underlying conditions resulting in frequent exposure to the healthcare system. However, previous studies have not thoroughly investigated whether HA-MRSA-CO has characteristics resembling those of CA-MRSA or hospital-onset, healthcare-associated MRSA (HA-MRSA-HO) infection. METHODS A multicenter, retrospective study was conducted to analyze the clinical and microbiological data of patients with clinical isolates of MRSA from nine hospitals in Taiwan. RESULTS In total, 203 patients with MRSA isolates, including 27 patients with CA-MRSA (13.3%), 59 with HA-MRSA-CO (29.1%), and 117 with HA-MRSA-HO (57.6%), were studied. Compared to HA-MRSA-HO isolates, the CA-MRSA and HA-MRSA-CO isolates were associated with a higher proportion of skin and soft tissue infections (81.8% and 65.3% vs. 40.5%, p=0.001 and p=0.002) as well as lesser rate of resistance to ciprofloxacin (33.3% and 50.9% vs. 74.4%, p<0.001 and p=0.002), gentamicin (44.4% and 64.4% vs. 84.6%, p<0.001 and p=0.002), and trimethoprim/sulfamethoxazole (33.3% and 42.4% vs. 58.1%, p=0.02 and p=0.048), and a lower 30-day all-cause mortality rate (7.4% and 0% vs. 20.9%, p<0.001). Most of the CA-MRSA isolates were classified as staphylococcal cassette chromosome mec (SCCmec) type VT (11/27, 40.7%), whereas most HA-MRSA-HO isolates were classified as SCCmec type III (66/117, 56.4%). CONCLUSION The CA-MRSA, HA-MRSA-CO, and HA-MRSA-HO clinical isolates significantly differed in their clinical presentations and molecular characteristics.