Wei-Chuan Hsieh

Antimicrobial drug resistance in pathogens causing nosocomial infections at a university hospital in Taiwan, 1981-1999.

To determine the distribution and antimicrobial drug resistance in bacterial pathogens causing nosocomial infections, surveillance data on nosocomial infections documented from 1981 to 1999 at National Taiwan University Hospital were analyzed. During this period, 35,580 bacterial pathogens causing nosocomial infections were identified. Candida species increased considerably, ranking first by 1999 in the incidence of pathogens causing all nosocomial infections, followed by Staphylococcus aureus and Pseudomonas aeruginosa. Candida species also increased in importance as bloodstream infection isolates, from 1.0% in 1981-1986 to 16.2% in 1999. The most frequent isolates from urinary tract infections were Candida species (23.6%), followed by Escherichia coli (18.6%) and P. aeruginosa (11.0%). P. aeruginosa remained the most frequent isolates for respiratory tract and surgical site infections in the past 13 years. A remarkable increase in incidence was found in methicillin-resistant S. aureus (from 4.3% in 1981-1986 to 58.9% in 1993-1998), cefotaxime-resistant E. coli (from 0% in 1981-1986 to 6.1% in 1993-1998), and cefotaxime-resistant Klebsiella pneumoniae (from 4.0% in 1981-1986 to 25.8% in 1993-1998). Etiologic shifts in nosocomial infections and an upsurge of antimicrobial resistance among these pathogens, particularly those isolated from intensive care units, are impressive and alarming.

Secular trends in the epidemiology of nosocomial fungal infections at a teaching hospital in Taiwan, 1981 to 1993.

OBJECTIVE To describe the incidence and patterns of nosocomial fungal infection in a large teaching hospital in Taiwan. DESIGN Prospective, hospitalwide nosocomial surveillance data from 1981 through 1993 were analyzed to show the secular trend in nosocomial fungal infection rates and to identify the most common pathogens and sites of infection (other than skin) in this hospital. SETTING AND PATIENTS The National Taiwan University Hospital is a medical school-affiliated hospital in the city of Taipei, Taiwan, with a 1200-bed capacity before 1991 and 1500 beds since 1992. It provides both primary and tertiary medical care. RESULTS The overall nosocomial fungal infection rate rose from 0.9 infections per 1000 discharges in 1981 to 6.6 per 1000 discharges in 1993, with the highest rate at the medical intensive-care unit (26.5/1000 discharges in 1993). This increase in infection rate was found at four major anatomic sites of infection, particularly including the bloodstream (0.08-2.19/1000 discharges) and the urinary tract (0.36-2.95/1000 discharges). Of 256 pathogens causing nosocomial fungemia from 1981 through 1993, Candida albicans was the most commonly isolated (50.8%), followed by Candida tropicalis (17.6%). Candida parapsilosis (11.7%), and Candida glabrata (8.2%). As compared to isolates from 1981 through 1988, the proportion of C parapsilosis and C glabrata isolated between 1989 and 1993 increased more than sixfold and fourfold, respectively. The increasing importance of fungal infections was confirmed further by the increased use of amphotericin B and azoles in this hospital. CONCLUSIONS Candida species and other yeasts have become a prominent cause of nosocomial infections in this hospital. These fungal pathogens accounted for a higher proportion of nosocomial bloodstream and urinary infections than any single bacterial species. Therefore, it is important to conduct a prospective epidemiological study and to establish in vitro antifungal susceptibility testing to enhance efforts to control nosocomial fungal infections and to minimize the risk of emergence of antifungal resistance.

Emerging fluoroquinolone-resistance for common clinically important gram-negative bacteria in Taiwan

The in vitro antimicrobial activity of the three most commonly used fluoroquinolones (norfloxacin, ofloxacin and ciprofloxacin) was measured for 2235 isolates of seven common pathogenic gram-negative bacteria. Collected from a major teaching hospital in Taiwan during the years 1985-86, 1989-90, and 1996-97, the samples were evaluated using the agar dilution method. The overall susceptibility to fluoroquinolones has decreased rapidly after the wide use of these antimicrobial agents. Isolates of Escherichia coli and Morganella morganii proved quite susceptible to the fluoroquinolones until 1996. By 1996-97, 20% of the bacteria had become resistant to the fluoroquinolones. Activity against Klebsiella pneumoniae and Proteus mirabilis remained excellent, however, with more than 90% of the isolates susceptible during the survey period. Interestingly, some strains of Serratia marcescens and Pseudomonas aeruginosa were demonstrating in vitro resistance even before the fluoroquinolones were launched in Taiwan. This resistance increased rapidly, with around 20-30% of S. marcescens isolates fluoroquinolone-resistant by 1996-1997. After the introduction of the fluoroquinolones, resistance was demonstrated for about 15% of the P. aeruginosa isolates, and 20% of Enterobacter cloacae isolates, with the susceptibility rate remaining steady state through the 1990s. Different pulsed-field gel electrophoresis patterns have been demonstrated for most fluoroquinolone-resistant isolates, suggesting that the increased resistance was not due to the spread of a single clone. We conclude a trend of increasing fluoroquinolone resistance for many common gram-negative bacteria in Taiwan, especially in recent years. Appropriate use of the new fluoroquinolones should be encouraged in order to prevent the rapid emergence and increase of fluoroquinolone-resistant bacteria.

High Prevalence of Antibiotic Resistance of Common Pathogenic Bacteria in Taiwan

We analyzed the antimicrobial susceptibilities of all clinical isolates of 14 common pathogenic bacteria recovered from patients in eight medical centers in Taiwan during 1995 and 1996. Susceptibility to commonly used antimicrobial agents was tested by the disk diffusion method as recommended by the National Committee for Clinical Laboratory Standards. Of the Staphylococcus aureus isolates, 59.3% and 62% were oxacillin-resistant in 1995 and 1996, respectively, whereas 63.2% of the coagulase-negative staphylococci isolates during the study period were oxacillin-resistant. The rate of penicillin-resistance among Streptococcus pneumoniae isolates was 39.7% in 1995 and 53.7% in 1996. Macrolide-resistance was found in 71.4%, 42.1%, and 46.7% of S. pneumoniae, beta-hemolytic streptococci, and viridans streptococci, respectively, in 1996. Less than 2% of the enterococcal isolates were vancomycin resistant, but 77% of them were gentamicin resistant. Resistance to gentamicin was also common in Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Various degrees of resistance to ampicillin, piperacillin, cephalosporins, aztreonam, and ciprofloxacin were detected in Enterobacteriaceae, P. aeruginosa, and A. baumannii. More than 55% of Haemophilus influenzae isolates were ampicillin resistant. In summary, resistance to many antimicrobial agents in various common pathogenic bacteria is very common in Taiwan. Our results implicate that antibiotic resistance in the developing countries need to be monitored closely.

Clinical features and in vitro susceptibilities of two varieties of Cryptococcus neoformans in Taiwan

One hundred years after introduction of the Eucalyptus tree to Taiwan, a predominantly subtropical island, we analyzed clinical and microbiological data of 59 patients with Cryptococcus neoformans infection hospitalized at National Taiwan University Hospital during 1982 to 1997. There were 38 (64.4%) cases of cryptococcosis caused by the var. neoformans and 21 (35.6%) caused by the var. gattii. Thirty-three patients (55.9%) had impaired T cell function, which included 12 patients with acquired immunodeficiency syndrome (AIDS). Eleven of the 12 patients with AIDS were diagnosed after 1995, and 11 cases were caused by var. neoformans. Minimum inhibitory concentrations (MICs) determined by the NCCLS broth microdilution method using antibiotic medium 3 improved the discrimination of in vitro susceptibility against amphotericin B and demonstrated that var. gattii isolates were less susceptible (geometric means 0.25 microg/ml versus 0.64 microg/ml, P < 0.001). In addition, a higher proportion of var. gattii were less susceptible to flucytosine as compared with var. neoformans (35.0% versus 64.9%, P = 0.030). There was no seasonal clustering for isolation of var. neoformans, though infections caused by var. gattii peaked in July and August. Compared with the first study of cryptococcosis (1957-1972) at NTUH, this study demonstrated the increase in immunocompromised and elderly patients, as well as a higher proportion of Cryptococcus isolated from blood or bone marrow. Facing the increasing adaptive plantation of Eucalyptus in Taiwan, the importance of field study regarding the role of Eucalyptus plantations in Taiwan and occurrence of cryptococcosis in human beings cannot be over-emphasized.

In vitro activites of antimicrobial agents, alone and in combination, against Acinetobacter baumannii isolated from blood

In vitro activities of 15 antimicrobial agents against 90 strains of Acinetobacter baumannii isolated from blood cultures from hospitalized patients were determined using the agar dilution method. Imipenem, ofloxacin, and ciprofloxacin had the best antimicrobial activity with minimum inhibitory concentrations (MIC50s) of 0.25 mu g/ml and MIC90s of 0.5-1 mu g/ml. beta-lactam antibiotics other than imipenem had poor activity, with MIC50s ranging from 8 to 64 mu g/ml and MIC90s from 32 to > or = 256 mu g/ml. The checkerboard titration method was used to study the effects of combination of two antimicrobial agents. Combinations of ceftazidime, aztreonam, imipenem, or ciprofloxacin with amikacin showed either synergistic effects or partial synergistic effects for 40.9%-86.4% of 22 tested strains. The best in vitro activity was observed with the combination of imipenem and amikacin. No antagonistic effects were observed with the combination of imipenem and amikacin. Synergistic effects were confirmed by time-kill curve studies. In conclusion, imipenem, ofloxacin, and ciprofloxacin were the three most active agents against human blood isolates of A. baumannii. The combination of a beta-lactam or ciprofloxacin with amikacin was synergistic for some of the isolates.

Increasing nosocomial infections of methicillin-resistant Staphylococcus aureus at a teaching hospital in Taiwan

Methicillin-resistant Staphylococcus aureus (MRSA) is a worldwide important pathogen in nosocomial infections. To investigate the extent of the problem in Taiwan, analysis for the period of 1981-1994 was carried out of prospective surveillance data from the National Taiwan University Hospital, a major university teaching hospital in Taiwan. The number of nosocomial MRSA infections increased from five in 1981 to 133 in 1994, and the incidence increased from 0.2 episodes/1000 discharges in 1981 to 2.9 episodes/1000 discharges in 1994. The most common infection site was surgical wounds, which accounted for 26.3% of total 577 episodes of nosocomial MRSA infections during the study period. However, bacteraemia has become more and more common during the past 14 years. MRSA infections occured more frequently in patients stayed in the burn unit and other intensive care units than in the general wards. Other than oxacillin, the resistance rate to many other antibiotics also increased in S. aureus strains causing nosocomial infections in this hospital. Vancomycin remained active to all these S. aureus strains, even until 1994.

Invasive pulmonary pseudallescheriasis with direct invasion of the thoracic spine in an immunocompetent patient

Most invasive pseudallescheriasis infections have occurred in immunocompromised patients. The case of an immunocompetent patient with invasive pulmonary pseudallescheriasis and subsequent contiguous extension to the ribs and spine is reported. Aspergillosis was mistakenly diagnosed on histopathologic examination of the debrided tissue. Culture of the debrided tissue yieldedPseudallescheria boydii.

Bacteremia Due to Klebsiella oxytoca: Clinical Features of Patients and Antimicrobial Susceptibilities of the Isolates

Forty-three patients with Klebsiella oxytoca bacteremia were seen between July 1980 and June 1996 at National Taiwan University Hospital (Taipei, Taiwan). We retrospectively analyzed the clinical features of these patients and the antimicrobial susceptibilities of the 43 isolates recovered from them. Twenty-seven patients (63%) had community-acquired bacteremia, and 16 patients (37%) had polymicrobial bacteremia. The clinical syndromes included hepatobiliary infections (58% of patients), primary bacteremia (23%), intravascular device-associated infections (7%), urinary tract infections (5%), skin and soft-tissue infections (5%), and peritonitis (2%). Most of these patients (93%) had underlying diseases including hepatobiliary diseases (53%), neoplastic diseases (42%), and diabetes mellitus (16%). Eight patients (19%) had septic shock, and two (5%) had disseminated intravascular coagulation. Four patients (9%) died of K. oxytoca bacteremia. All isolates were susceptible to ampicillin/sulbactam, cefmetazole, imipenem, aminoglycosides, and quinolones, and 86% of the isolates were susceptible to cefazolin.

In vitro activities of antimicrobial agents, alone and in combinations, against Burkholderia cepacia isolated from blood

Burkholderia cepacia is a widespread, environmental gram-negative bacillus that is associated with nosocomial infections. This bacterium is considered to be an important pathogen in immunocompromised patients and is inherently resistant to multiple antimicrobial agents. To compare the activity of different antimicrobial agents and the potential of combinations against invasive strains of B. cepacia, we collected 36 isolates of B. cepacia from blood cultures and checked their susceptibilities to 13 antimicrobials by broth microdilution method. Most strains tested were susceptible to minocycline (94.4%), ceftazidime (86.1%), ciprofloxacin (83.3%), and trimethoprim-sulfamethoxazole (83.3%). All strains were resistant to aminoglycosides, and only some strains were susceptible to imipenem (16.7%), aztreonam (19.4%), moxalactam (25.0%), piperacillin (25.0%), and carbenicillin (47.2%). The effects of combinations of ceftazidime with amikacin, ceftazidime with ciprofloxacin, and ciprofloxacin with amikacin were assayed by checkerboard titration method. Synergistic effect was found in 28 out of 36 tested strains (77.8%), when ceftazidime was combined with amikacin, in 25 out of 36 strains (69.4%) when ceftazidime was combined with ciprofloxacin, and in only 8 out of 36 strains (22.2%) when ciprofloxacin was combined with amikacin.