What have we learnt from community-acquired infections in Hong Kong?

J. M. Ling*, A. W. Lam, E. W. Chan and A. F. Cheng

Department of Microbiology, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China

Received 6 October 2002; returned 4 December 2002; revised 14 January 2003; accepted 21 January 2003


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
This study was initiated throughout Hong Kong, to reveal the characteristics of community-acquired infections. All specimens collected by general practitioners from infected patients were followed prospectively, and those that were culture-positive were analysed. Four thousand seven hundred and forty-one specimens were collected from 3977 patients by 89 doctors from July 2000 to October 2001. The most common specimens were throat swabs (33%), urine (26%) and sputa (16%). The average culture-positive rate was 28%. The most common organisms were Escherichia coli (18%), ß-haemolytic streptococci (15%) and Staphylococcus aureus (12%). Fluoroquinolone resistance was relatively high (up to 35%) in organisms commonly causing urinary tract infection (E. coli, Proteus and Morganella). Although none of the pneumococci was resistant to penicillin 1 mg/L, the proportion with intermediate resistance (0.1–1 mg/L) was alarming (81%). There were three strains of methicillin-resistant S. aureus. A decrease in ampicillin resistance but a high prevalence of macrolide resistance were noted in Haemophilus influenzae. All Neisseria gonorrhoeae isolates were resistant to penicillin, up to 79% to the fluoroquinolones, 15% to spectinomycin, but all were susceptible to ceftriaxone. Respiratory pathogens (Streptococcus pneumoniae, ß-haemolytic streptococci and H. influenzae) were relatively susceptible to the newer fluoroquinolones (0–2%, 0.5–6% and 2% resistant, respectively) or third-generation cephalosporins (0–2% resistant). The distribution of organisms and their antibiotic resistance varied over time. Thus frequent surveillance is needed to provide information on the drugs of choice for different infections.

Keywords: community-acquired infections, antimicrobial susceptibilities


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Antibiotics are frequently prescribed in hospital and general practice. However, they are often administered before the pathogen’s culture and sensitivity results are known. As the distribution of causative organisms and bacterial resistance rates vary in time and place, recent local data are essential to guide clinicians to the best choice of treatment. In this manner, not only are patients treated with the correct antibiotic, but misuse and overuse of antibiotics, which lead to rapid development and spread of resistance, can be minimized. In addition, early detection of antibiotic resistance can be achieved by surveillance and rapid laboratory identification.1 Data from different geographical regions provide important information on the epidemiology of pathogens and antibiotic resistance.

In Hong Kong, healthcare is provided by the Hospital Authority, the Department of Health and private doctors. The Hospital Authority manages hospitals and provides follow-up services to discharged patients, whereas the Department of Health mainly provides consultation to general outpatients. Services provided by these two organizations are largely subsidized by the government, and patient waiting times are frequently long. Patients with acute symptoms, who can afford higher consultation fees, may visit private doctors and hospitals to obtain a faster service. There are no particular criteria by which patients select private doctors, other than convenience (closeness of clinics to home), word-of-mouth by other patients and competititive consultation fees. According to official figures for 2001, there are 1.5 doctors per 1000 population (http://www.info.gov.hk/censtatd/eng/hkstat/hkinf/health/health_4_index.html). With a population of 6.7 million, there are ~10 050 doctors, of whom an estimated 3500 are primary care doctors.2

Published local susceptibility results are usually based on hospital isolates,37 whereas reports on community-acquired organisms are few. There is only one detailed report on the susceptibility patterns of general practice organisms in Hong Kong.8 There may be greater demand for such data in general practice than in hospitals, since specimens are often not submitted for culture from general practitioners.

In this study of the Hong Kong region, we aimed to investigate prospectively culture-positive infections in patients visiting general practitioners, and to determine the susceptibility of these isolates to commonly used and newer antimicrobial agents.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
To avoid bias in the survey, all Hong Kong general practitioners were invited to participate. A letter of invitation was sent to every doctor on the Hong Kong medical registry with a commercial address. General practitioners usually have their clinics on the ground floor of commercial buildings or shopping malls, whereas specialists are frequently located on upper floors. This was one of the criteria for choosing participants. Before the study, general practitioners were briefed to take specimens according to specified guidelines9 from every patient whom they suspected of having an infection. To maintain the enthusiasm of the doctors during the study, collated results were distributed to them monthly. The specimens were collected by laboratory staff and cultured in the microbiology laboratory using standard methods.9 Isolated organisms were identified according to standard procedures,9 and antimicrobial susceptibilities determined by the disc diffusion test.10 Culture and susceptibility results were sent to the requesting doctors as soon as available. All isolates were stored for the determination of MIC of different antibiotics (as listed in Tables 35) by an agar dilution method.11 ß-Lactamase production in Haemophilus influenzae and Neisseria gonorrhoeae was detected using a cefinase disc (Becton-Dickinson & Co., MD, USA). Comparisons of antibiotic resistance levels were made by the {chi}2 test.


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Table 3.  Percentage resistance of Gram-negative bacteria to 22 antimicrobial agents in 1991 and 2000
 

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Table 5.  Percentage resistance of Gram-positive bacteria to antimicrobial agents in 1991 and 2000
 

    Results
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
A total of 4741 specimens were sent from 89 community doctors during the 15 months of July 2000–October 2001. Of these specimens, 4679 were non-duplicates from 3977 patients. The male to female ratio was 1:1.23 and the age distribution of the patients is shown in Figure 1. Most patients belonged to the 30–39 year age group (19%), followed by 20–29 (17%) and 40–49 (15%). These together (20–49-year-olds) constituted >50% of all patients.



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Figure 1. Age distribution of patients.

 
The distribution of patients seen by the doctors is shown in Figure 2. The majority of doctors (70/89, 79%) sent specimens from 1–49 patients whom they suspected of infection, whereas 19 sent specimens from 50–512 patients.



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Figure 2. Number of doctors versus number of patient specimens provided.

 
Distribution of specimens and bacteria isolated

Table 1 shows the type and distribution of specimens. The most common specimen was a throat swab (33%), followed by urine (26%) and sputum (16%). The other specimens constituted 6% or less. The culture-positive rate ranged from 17% (stool or rectal swab) to 80% (ear swab), with an average of 28%. Wound swab and pus gave the next highest culture-positive rate of 68% and 57%, respectively.


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Table 1.  Types of specimens collected and culture-positive rates
 
The types of bacteria isolated from the specimens are shown in Table 2. Only single-patient isolates were included. Of the 1371 strains isolated, 50% were Gram-negative bacteria and 41% Gram-positive bacteria. The most common organism was Escherichia coli (18%), followed by Staphylococcus aureus (12%), Candida albicans (9%) and ß-haemolytic streptococci group G (8%). However, all ß-haemolytic streptococci (including groups A, C and G) constituted 15% of the strains isolated. Each of the other organisms constituted <=6%.


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Table 2.  Distribution of bacteria isolated from different specimens
 
The majority of E. coli were isolated from urine (84%), and 95% of C. albicans were from high vaginal swabs. More than 90% of ß-haemolytic streptococci were from throat swabs; however, six group A ß-haemolytic streptococcus strains were isolated from pus. Thirty-one per cent of S. aureus were from pus or wounds, whereas similar proportions (23–24%) were from the throat and other areas. H. influenzae was mainly isolated from sputum (85%), whereas other Gram-negatives such as Pseudomonas aeruginosa, enterobacters, klebsiellae and acinetobacters were mainly isolated from respiratory specimens (56–83%). Forty-seven isolates of N. gonorrhoeae were obtained, and all except two were from male patients.

Antimicrobial resistance of Gram-negative bacteria

More than 60% of E. coli isolates were resistant to ampicillin, but only 16% were resistant in the presence of clavulanic acid (Table 3). More than 50% were resistant to 4 mg/L cefuroxime, but <5% to the third-generation cephalosporins ceftriaxone or cefotaxime, and none to ceftazidime or imipenem. Thirty per cent were resistant to gentamicin, 2% to netilmicin and 0% to amikacin. Although 50% were resistant to nalidixic acid, 16–25% were resistant to the fluoroquinolones. Forty or more per cent were resistant to the other antibiotics, such as trimethoprim, sulfamethoxazole, chloramphenicol or tetracycline. Significantly more E. coli isolates were resistant to cefuroxime (P < 0.01), gentamicin, nalidixic acid and ofloxacin (P < 0.05) in this study, as compared with the previous report.8

Only 3% of Klebsiella spp. were resistant to the combination of ampicillin and clavulanic acid (Table 3). Ten per cent or fewer were resistant to cefuroxime or cefamandole, but none was resistant to the third-generation cephalosporins or imipenem. Resistance to aminoglycosides or the fluoroquinolones was low, being 0–5%. Although fewer isolates were resistant to gentamicin, nalidixic acid or ofloxacin as compared with our previous study,8 the difference was not significant (P > 0.05).

More than 60% of Proteus spp. and Morganella spp. were resistant to ampicillin, but none was resistant in the presence of clavulanic acid (Table 3). More than 10% (12–18%) were resistant to the fluoroquinolones, but 35% were resistant to gemifloxacin. All were susceptible to ceftriaxone, cefotaxime, imipenem, netilmicin and amikacin. Significantly more isolates of the present study were resistant to ampicillin or ceftazidime as compared with the previous study (P < 0.05).8

Resistance to the third-generation cephalosporins or aminoglycosides was generally low (4–6%) in the enterobacters (Table 3). Only 2% were resistant to the fluoroquinolones, including the newer ones, such as moxifloxacin or gemifloxacin. Nine per cent of salmonellae were resistant to ampicillin, whereas all were susceptible to ampicillin + clavulanic acid, the second- and third-generation cephalosporins, aminoglycosides and the fluoroquinolones; however, 18% were resistant to chloramphenicol.

Antibiotic resistance in P. aeruginosa and acinetobacters was low, with all strains being susceptible to ceftazidime, imipenem, meropenem, aminoglycosides or fluoroquinolones (Table 3).

Less than 40% of H. influenzae were resistant to ampicillin, but only one isolate remained resistant to ampicillin in the presence of clavulanate (Table 4). ß-Lactamase was detected in nine isolates, which represented 43% of ampicillin-resistant strains and 14% of all isolates. Forty-seven per cent were resistant to cefaclor and 11–19% to chloramphenicol or tetracycline. All were resistant to erythromycin, 69% to clarithromycin, but only 2–3% were resistant to the second- and third-generation cephalosporins and fluoroquinolones. Significantly fewer strains were resistant to ampicillin than in the previous study (P < 0.01).


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Table 4.  Percentage resistance of Haemophilus influenzae and Neisseria gonorrhoeae to antimicrobial agents in 1991 and 2000
 
All the 47 isolates of N. gonorrhoeae were resistant to penicillin and 18% of these produced ß-lactamase. More than 90% were resistant to tetracycline, ciprofloxacin or ofloxacin, 58–64% to 0.5 mg/L sparfloxacin or gemifloxacin and 36–39% to 2 mg/L levofloxacin or 1 mg/L moxifloxacin (Table 4). However, none was resistant to ceftriaxone and 15% were resistant to spectinomycin.

Antimicrobial resistance of Gram-positive bacteria

Table 5 shows antimicrobial resistance in S. aureus, Streptococcus pneumoniae, ß-haemolytic streptococci and enterococci. Three (2%) strains of S. aureus were resistant to methicillin. Resistance to aminoglycosides (0–5%) or fluoroquinolones (2%) was low. None was resistant to vancomycin. More than 80% of S. pneumoniae were resistant to 0.06 mg/L penicillin, all of which had MICs 0.12–0.25 mg/L. Resistance to clarithromycin, erythromycin or tetracycline was high (90%), but none was resistant to ampicillin, cefotaxime or ceftriaxone. Resistance to the fluoroquinolones was also low, with 2% to sparfloxacin or gemifloxacin, but 0% to levofloxacin or moxifloxacin. Although 10% of ß-haemolytic streptococci were resistant to penicillin, all belonged to groups C and G. Resistance to levofloxacin or moxifloxacin (0.5–1%) was low, but higher to gemifloxacin, ofloxacin or sparfloxacin (4–6%). However, resistance to clarithromycin was high (33%). None of the enterococci was resistant to 8 mg/L penicillin or ampicillin and vancomycin, and <10% (4–9%) were resistant to fluoroquinolones.


    Discussion
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Comprehensive studies on community-acquired pathogens are few,12 although there are numerous surveillance reports on organisms causing specific infections, such as pneumonia13,14 or urinary tract infection.15,16 Our first local survey of antibiotic resistance in the community was performed in 1991.8 The survey methods used were the same as for the present study, but financial restrictions meant that only doctors practising in the New Territories were included (constituting 88% of the land area of Hong Kong and housing about half of the total population). The present study was initiated to provide up-to-date information on the distribution and antimicrobial susceptibilities of all community-acquired organisms in Hong Kong. Eighty-nine community doctors practising in Hong Kong (spanning an area of 1100 km2 and serving a population of more than six million) agreed to participate. They were to take appropriate specimens, according to specified guidelines,9 from patients thought to be infected, and the specimens were collected by laboratory staff the same or the next day and cultured in the laboratory. The distribution of patients was normal, the majority being within the 20–49 year age range. This is similar to the age structure of the general population of Hong Kong, where people in the 15–54 year age range constitute 64% of the population, whereas those aged 0–14 years constitute 16% (http://www.info.gov.hk/hkfacts/popula.pdf). Most doctors (79%) sent specimens from <50 patients, although there were nine who sent specimens from 100–>500 patients. This collection was therefore representative of community-acquired infections in Hong Kong.

Throat swabs were the most common specimens collected, followed by urine. However, throat swabs together with sputa constituted 49% of all specimens, whereas urine constituted 26%; both figures are comparable to that reported in our last study (48% and 28%, respectively).8 Thus, most patients sought medical attention because of respiratory problems, whereas urinary symptoms were the next most common complaint. Urinary tract infection is more commonly seen in females, and this may have led to the large number of urine samples and high vaginal swabs collected from females, and the resulting male:female ratio = 1:1.23.

Also, for a similar reason (the large numbers of throat swab and urine collected), it is not surprising that ß-haemolytic streptococci and E. coli top the list of organisms isolated. However, this is in contrast to what was observed in our last study when H. influenzae was the most common organism isolated, with E. coli and ß-haemolytic streptococci being the third and seventh most common, respectively.8 The small number of H. influenzae strains isolated could indicate that chest infections caused by this organism had decreased in importance. Previously, 13% of sputa yielded H. influenzae,8 whereas only 9% yielded the organism in this study. It is difficult to speculate why this is so as H. influenzae type b vaccination was not given routinely. The isolation of enterobacteria and non-enterobacteria, such as P. aeruginosa and acinetobacters from respiratory specimens probably represented colonization rather than true pathogens. The comparatively large numbers of N. gonorrhoeae isolated from urethral swabs indicated the importance of gonorrhoea in the community.

Penicillin resistance in S. pneumoniae was indeed a problem in Hong Kong (81%), with an almost five-fold increase over 10 years,8 although the organism was mainly isolated from respiratory specimens and the resistance was low-level (MICs < 1 mg/L). The third-generation cephalosporins and the newer fluoroquinolones remained active against this organism. Accumulating evidence has shown that patients with pneumonia caused by pneumococci with intermediate susceptibility to penicillin respond well to treatment with sufficient doses of intravenous penicillin.1719 However, local penicillin concentration may not be high enough against infections by such strains at other sites, for example meningitis.20

Ampicillin resistance remained at 60–70% in E. coli. However, fluoroquinolone resistance to ofloxacin increased considerably, from 6–22%,8 and from 0–18% in Proteus and Morganella, the organisms commonly causing urinary tract infection. Whether this was related to the frequent prescription of fluoroquinolones for treatment of this infection requires further investigation. Although resistance to the third-generation cephalosporins was not a problem in the Gram-negatives, these mainly intravenous drugs would not be a good choice for treating community-acquired infections.

There were three strains of methicillin-resistant S. aureus (MRSA), indicating that MRSA was not only a hospital phenomenon.21,22 Our enterococci were mainly isolated from urine and had remained fairly susceptible to fluoroquinolones. Vancomycin-resistant enterococci (VRE) were not present in our collection. Coque et al.23 also did not find any VRE in their survey of healthy volunteers.

It is surprising to find a significant decrease in ampicillin resistance in H. influenzae (from 64%8 to 39%, P < 0.01) although the proportion of ß-lactamase-producing strains were similar (40%24 versus 43%) and were also similar to that reported by Doern et al.25 However, resistance to macrolides remained high, even to clarithromycin (69%). Second- and third-generation cephalosporins and the fluoroquinolones remained active (<=3% resistance).

Although 10% of ß-haemolytic streptococci were resistant to penicillin, none was group A. The newer fluoroquinolones would probably be the next drugs of choice, rather than the macrolides, for infections caused by this group of organisms.

Penicillin, as in other parts of the world, would no longer be effective in treating gonorrhoea.2628 However, the proportion of ß-lactamase-producing strains was much lower in our study: 18% versus 75% in Indonesia26 and 37% in Mongolia.27 With the considerable high level of resistance to fluoroquinolones (>30%) and spectinomycin (15%), ceftriaxone would be the only drug of choice.

In order to investigate patterns of antibiotic use, doctors were asked to indicate the antibiotics they would prescribe to individual patients. However, since this was voluntary, and possibly inaccurate, detailed results are not included here, but will be discussed briefly. Available information showed that ampicillin was the most commonly prescribed antibiotic, followed by cefuroxime, co-amoxiclav, cloxacillin, cefaclor, co-trimoxazole and clarithromycin, each constituted 5–16% of the total prescription given (some patients received more than one antibiotic). A total of 2934 patients received antibiotics, although only 1293 specimens became culture-positive (Table 1). There was therefore much overuse of antibiotics. This may have been because patients demanded excess drugs, since the consultation fee often included the cost of medicine. A recent article2 indicated that 22% of 801 doctors who responded to a survey on antibiotic usage felt that they were prescribing antibiotics too often for upper respiratory infections. We suggest that antibiotics should only be prescribed if there is a high suspicion of infection. Specimens should be taken for culture and antibiotics stopped, if appropriate, for instance when the culture results are negative. First-line antibiotics should be chosen and, according to antibiotic susceptibility results, the duration of the course of treatment should be adequate, and probably involve cycling of antibiotics.29

To conclude, in our study, fluoroquinolone resistance was relatively high in organisms causing urinary tract infection. Intermediate penicillin resistance in pneumococci was alarming. The newer fluoroquinolones, or third-generation cephalosporins, would be active against organisms causing respiratory infections. Antibiotic resistance was on the rise, although the trend varied in different organisms. The distribution of organisms and their antibiotic resistance varied, so that frequent surveys are warranted to provide information on the drugs of choice for different infections.


    Acknowledgements
 
We thank K. H. Kwan, C. Y. Chan, K. T. Wong and W. K. Charm for their technical assistance, Dr W. L. Lo, Dr K. M. So and Professor J. A. Dickinson who helped recruit some of the general practitioners, and all the doctors who participated in this study. Levofloxacin was a gift from Hong Kong Medical Supplies Ltd, Hong Kong, moxifloxacin from Bayer AG, Germany, and gemifloxacin from GlaxoSmithKline, UK. This study was supported by Health Care & Promotion Fund (reference no 212921).


    Footnotes
 
* Corresponding author. Tel: +852-2632-3333; Fax: +852-2647-3227; E-mail: meilunling{at}cuhk.edu.hk Back


    References
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
1 . Hughes, J. M. & Tenover, F. C. (1997). Approaches to limiting emergence of antimicrobial resistance in bacteria in human populations. Clinical Infectious Diseases 24, Suppl. 1, S131–5.[ISI][Medline]

2 . Lam, K. F. & Lam, T. P. (2002). Antibiotic wastage costs in Hong Kong. Hong Kong Practitioner 24, 580–1.

3 . Ling, J. M. & Cheng, A. F. (1995). Antimicrobial resistance of clinical isolates from 1987 to 1993 in Hong Kong. Hong Kong Medical Journal 1, 212–8.

4 . Ling, J. M., Ng, T. K. C., Cheng, A. F. & Norrby, S. R. (1996). Susceptibilities to 23 antimicrobial agents and ß-lactamase production of blood culture isolates of Acinetobacter sp in Hong Kong. Scandinavian Journal of Infectious Diseases, Suppl. 101, 21–5.

5 . Kam, K. M., Luey, K. Y., Fung, S. M., Yiu, P. P., Harden, T. J. & Cheung, M. M. (1995). Emergence of multiple-antibiotic-resistant Streptococcus pneumoniae in Hong Kong. Antimicrobial Agents and Chemotherapy 39, 2667–70.[Abstract]

6 . Chu, Y.-W., Houang, E. T. S., Lyon, D. J., Ling, J. M., Ng, T.-K. & Cheng, A. F. (1998). Antimicrobial resistance in Shigella flexneri and Shigella sonnei in Hong Kong, 1986 to 1995. Antimicrobial Agents and Chemotherapy 42, 440–3.[Abstract/Free Full Text]

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9 . Murray, P. R. (Ed.). (1999). Manual of Clinical Microbiology, 7th edn. ASM Press, Washington, DC, USA.

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11 . National Committee for Clinical Laboratory Standards. (1997). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically: Approved Standard M7-A4. NCCLS, Villanova, PA, USA.

12 . Cullmann, W. (1996). Comparative evaluation of orally active antibiotics against community-acquired pathogens: results of eight European countries. Chemotherapy 42, 11–20.[ISI][Medline]

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14 . Melo-Cristino, J., Fernandes, M. L., Serrano, N. & The Portuguese Surveillance Group for the Study of Respiratory Pathogens. (2001). A multicenter study of the antimicrobial susceptibility of Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis isolated from patients with community-acquired lower respiratory tract infections in 1999 in Portugal. Microbial Drug Resistance—Mechanisms Epidemiology & Disease 7, 33–8.

15 . Gupta, K., Hooton, T. M. & Stamm, W. E. (2001). Increasing antimicrobial resistance and the management of uncomplicated community-acquired urinary tract infections. Annals of Internal Medicine 135, 41–50.[Abstract/Free Full Text]

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17 . Friedland, I. R. (1995). Comparison of the response to antimicrobial therapy of penicillin-resistant and penicillin-susceptible pneumococcal disease. Paediatric Infectious Diseases 14, 885–90.[ISI]

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19 . Campbell Jr, G. D. & Silberman, R. (1998). Drug-resistant Streptococcus pneumoniae. Clinical Infectious Diseases 26, 1188–95.[ISI][Medline]

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21 . O‘Brien, F. G., Pearman, J. W., Gracey, M., Riley, T. V. & Grubb, W. B. (1999). Community strain of methicillin-resistant Staphylococcus aureus involved in a hospital outbreak. Journal of Clinical Microbiology 37, 2858–62.[Abstract/Free Full Text]

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23 . Coque, T. M., Tomayko, J. F., Ricke, S. C., Okhyusen, P. C. & Murray, B. E. (1996). Vancomycin-resistant enterococci from nosocomial, community, and animal sources in the United States. Antimicrobial Agents and Chemotherapy 40, 2605–9.[Abstract]

24 . Ling, J. M., Lam, A. W. & Cheng, A. F. (1993). Prevalence of ampicillin-resistant Haemophilus influenzae in community-acquired infections in Hong Kong. Journal of Antimicrobial Chemotherapy 32, 346–7.[ISI][Medline]

25 . Doern, G. V., Brueggemann, A. B., Pierce, G., Holley, H. P., Jr & Rauch, A. (1997). Antibiotic resistance among clinical isolates of Haemophilus influenzae in the United States in 1994 and 1995 and detection of ß-lactamase-positive strains resistant to amoxicillin-clavulanate: results of a national multicenter surveillance study. Antimicrobial Agents and Chemotherapy 41, 292–7.[Abstract]

26 . Lesmana, M., Lebron, C. I., Taslim, D., Tjaniadi, D., Subekti, D., Wasfy, M. O. et al. (2001). In vitro antibiotic susceptibility of Neisseria gonorrhoeae in Jakarta, Indonesia. Antimicrobial Agents and Chemotherapy 45, 359–62.[Abstract/Free Full Text]

27 . Lkhamsuren, E., Shultz, T. R., Limnios, E. A. & Tapsall, J. W. (2001). The antibiotic susceptibility of Neisseria gonorrhoeae isolated in Ulaanbaatar, Mongolia. Sexually Transmitted Infections 77, 218–9.[Free Full Text]

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