Table 1 shows the years that selected antibiotics were approved in Taiwan. These antibiotics are now widely used to treat various infections, including community-acquired and nosocomial infections. Until now, two gylcopeptides (vancomycin and teicoplanin), two carbapenems (imipenem and meropenem), four macrolides (erythromycin, roxithromycin, clarithromycin, and azithromycin), and six quinolones (nalidixic acid, norfloxacin, ofloxacin, lomefloxacin, ciprofloxacin, and levofloxacin) have been available for clinical use in Taiwan. Most of these drugs were also readily available at drugstores without prescription before 1995.

The following drug-resistance data were collected from a nationwide resistance survey (Surveillance from Multicenter Antimicrobial Resistance in Taiwan ) of clinical isolates (including those recovered from hospitals and outpatients) from 12 major hospitals as well as isolates causing nosocomial infections from National Taiwan University Hospital (NTUH) in 2000 in Taiwan. These hospitals are located in different parts of the country. The number of beds in these hospitals ranged from 800 to 3,200. All these data were derived by using the disk-diffusion method (7).

Some dilution antimicrobial susceptibility and epidemiology studies, including ≥100 strains published in English-language journals from January 1995 through 2001, were also included. Rather than provide a comprehensive review of all resistance problems in Taiwan, our aim was to point out some of the more critical resistance problems threatening the treatment of infections caused by Staphylococcus species, S. pyogenes, Streptococcus pneumoniae, Enterococcus species, and Mycobacterium tuberculosis among the gram-positive pathogens, and Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Enterobacter species, Salmonella species, Campylobacter species, Pseudomonas aeruginosa, and Acinetobacter baumannii among the gram-negative pathogens. Resistance rates included in this review reflect both intermediate and fully resistant population. Table 2 summarizes the prevalence of antimicrobial resistance among clinical isolates (12 hospitals, including NTUH) and nosocomial isolates (from NTUH only) of some selected bacterial species. The ranges in numbers of clinical isolates of select bacteria (Table 2) recovered from these hospitals were as follows: Staphylococcus aureus, 1,889 to 7,516 isolates; beta-hemolytic streptococci, 335 to 1,102; S. pneumoniae, 138 to 461; enterococci, 509 to 3,676; H. influenzae, 427 to 602; E. coli, 1,734 to 9,553; K. pneumoniae, 950 to 3,226; E. cloacae, 427 to 1,426; nontyphoid Salmonella, 94 to 626; P. aeruginosa, 1,741 to 4,896; and A. baumannii, 896 to 2,434.

The overall prevalence of clinical isolates of PNSSP in 1999-2000 was 60% to 80%, including 20% to 30% penicillin-intermediate- and 40% to 50% penicillin-resistant strains (10–16). This prevalence of PNSSP was slightly lower than that in Korea and higher than that in most other geographic areas (15,16). All PNSSP were resistant to multiple antibiotics (13,16). This resistance was higher among nasopharyngeal isolates from children (12). Approximately 60% of the PNNSP isolates were also not susceptible to extended-spectrum cephalosporins and carbapenems (13). Most of these PNSSP belong to serotypes 23F, 19F, 6B, and 14 (13,15). Wide dissemination of multiple high-level penicillin-, extended-spectrum cephalosporin-, and macrolide-resistant clones as well as the Spain 23F clone contributes to the high rates of resistance to these drugs in clinical isolates of S. pneumoniae (14,17). Only one clinical isolate was reported to be resistant to fluoroquinolones (18).

The first clinical isolate of Van-A-phenotype VRE (E. faecalis) was found in 1995 (19). Since then, isolation of VRE remains rare and accounts for <3% of all clinical isolates of enterococci (20,21). The proportion of Enterococcus hospital isolates resistant to vancomycin in Taiwan is low compared with those in North America and Europe (22), a finding that needs further investigation. However, an increase in VRE isolation associated with the continuous widespread use of glycopeptides in a Taiwanese university hospital was observed (23). Furthermore, interhospital and nosocomial spread of some VRE clones, particularly one vanB2 E. faecium clone, or long-term persistence of multiple clones in hospitalized patients still exists (21,24). Although avoparcin has been approved for veterinary use since 1977, this agent has been banned in the farming industry since 2000 (24). Glycopeptide resistance has been found in some isolates of coagulase-negative staphylococci, particularly in S. simulans and S. warneri (25).

Figure

Figure. . A, Macrolides consumption (gram x 1000,000) in Taiwan and the trends of erythromycin-resistant group A Streptococcus (EM-R GAS), group B Streptococcus (EM-R GBS), and S. pneumoniae in National Taiwan University...

Under the increasing and highly selective pressure of macrolide usage in Taiwan, the prevalence of macrolide resistance and distribution of M-phenotype (mef gene-positive) among macrolide-resistant isolates vary among different streptococcal species (Figure) (26–31). More than 90% of the S. pneumoniae isolates were resistant to macrolides, and approximately two thirds exhibited high-level resistance (MLS_B phenotype-erm gene-positive) (29). However, macrolide resistance accounted for 50% to 60% of all clinical isolates of S. pyogenes, and a stepwise increase of proportion of M phenotype was clearly demonstrated (29).

Quinupristin-dalfopristin is not available for clinical use in Taiwan; nevertheless, the incidence of resistance to this agent was high (51%) in vancomycin-resistant E. faecium (25). Three resistant E. faecium isolates were recovered from animal sources (pigs) in Taiwan. Restricted use of virginiamycin, which has been widely used in animal feed for >20 years in this country, might be required to alleviate quinupristin-dalfopristin resistance among bacteria from human sources (25).

The prevalence of pulmonary tuberculosis (TB) in adults was 0.65% in 1993 and the associated death rate was 6.93 per 100,000 in 1998 (32). The overall incidence of isoniazid-resistant M. tuberculosis was 31.5%. The incidence of primary resistance (isolates from patients with newly diagnosed TB who had no prior history of anti-TB therapy or from patients whose anti-TB therapy was begun <2 weeks) was 12.0%; the incidence of acquired resistance (isolates from patients who had a prior history of anti-TB medication) was 63.0%. The overall incidence of MDRTB was 17.3% (primary resistance 1.6%; acquired resistance 46%) (33). An aggressive intervention program, such as expanded use of directly observed therapy, short course, is ongoing to improve the cure rate of TB and to decrease the resistance rate.

By the end of the 20th century, many measures to control resistance problems had been instituted in Taiwan. Antibiotics had been removed from the list of available nonprescription drugs at drugstores. Antibiotic interventions had been implemented in many hospitals, particularly in intensive-care units, to alleviate the high prevalence of resistance among nosocomial pathogens. In 2000, the Council of Agriculture in Taiwan prohibited the use of several antimicrobial agents (such as avoparcin, kanamycin, kitasamycin, lasalocid, spiramycin, salinomycin, and streptomycin), which had been widely used as growth promoters or prophylactic agents in animal husbandry in Taiwan during the past 2 to 3 decades, because they may select for critical forms of resistance in human pathogens in food-producing animals (54). Further research is ongoing to reduce the risk for increasing resistance in human pathogens caused by antibiotic use in animal husbandry. In the new millennium, the Center for Disease Control, Department of Health, in Taiwan, has made control of antimicrobial resistance a major goal. The two main tasks are to restrict use of antibiotics for trivial upper respiratory tract infections and to avoid inappropriate use of antibiotics for surgical prophylaxis.