CITATION: Keuleyan EE et al. 1997. Antibiotic resistance in two university hospitals in Sofia, Bulgaria. APUA Newsletter 15(3): 1,4-5.

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Antibiotic resistance in two university hospitals in Sofia, Bulgaria
Emma E Keuleyan, Yana H Haralambieva, Rayna P Gergova, Roumyana D Markovska and Ivan G Mitov
Medical University, Sofia, Bulgaria

Bulgaria, like many countries around the world, is experiencing an alarming increase in resistance to antibiotics, drugs that, until recently, were presumed to have endless powers against infection. This is particularly evident in the hospital setting, where resistant pathogens continue to be an increasing and persistent danger to the patient. Numerous symposia, congresses and roundtables have recently been dedicated to the issue of bacterial resistance in Bulgaria, and special emphasis is being placed on this health threat during the education of medical students. Still, it remains to be seen what effect these endeavors will have on the overall problem.

The range of antimicrobial agents prescribed in Bulgaria is broad. Tetracyclines are the most commonly used, followed by aminopenicillins, sulfamethoxazole-trimethoprim, aminoglycosides, chloramphenicol, penicillin, macrolides, cephalosporins, lincosamides and fluoroquinolones (2). In 1996, we documented and analyzed resistance patterns of various pathogens in two hospitals: the University Hospital for Orthopedics and Traumatology (UHOT) comprised of 220 beds, and the University Hospital St. I. Rilsky (UHSIR), with 200 beds. Of the 7,275 specimens delivered to our laboratory, 62% were urine, 11% were blood cultures, 11% were from upper respiratory tract (UTI) infections, 8% were from digestive tract infections, 4% from wounds and punctures, and 4% others. The positive specimens were 18%. Gram-negative isolates represented 83% of UTI and 56% of septicemia. The susceptibility results of the ten most prominent pathogens are illustrated in Figures 1-5.

Analysis of Resistance Patterns
E. coli (Figure 3) were the most frequently isolated organisms (62% urine), showing high resistance to aminopenicillins (75%), and tetracyline (51%). Roughly 40% of strains were resistant to acylureidopenicillins, and to first and second generation cephalosporins. Chloramphenicol resistance was documented in 16% of strains, and 11% were resistant to sulfamethoxazole-trimethoprim. These resistance patterns are most likely plasmid-mediated, the result of many years of overprescription and misuse of these drugs.

S. aureus, now the leading disease pathogen throughout the world (6), accounted for 36% of resistant organisms isolated (Figure 1). This is an increase of 10% over 1995. Eighty-seven percent of strains were resistant to penicillin, while nearly 40% showed resistance to tetracycline. Some methicillin-resistant strains were susceptible to rifampicin, Sulfamethoxazole-Trimethoprim, clindamycin, as well as to ciprofloxacin and gentamicin. As anticipated, coagulase-negative Staphylococcus (CNS) (Figure 1) showed polyresistance, and in an unexpected development, 2% of strains were resistant to vancomycin, whereas none showed resistance to this drug in 1995. Methicillin-resistant CNS is increasingly isolated from different clinics in Bulgaria.

Enterococci spp (Figure 2), most notably
E. faecalis, are increasingly isolated, and their resistance patterns need close monitoring (7). Of particular concern is a previously low level (4%) of resistance to vancomycin, noted in 1995, which jumped to 37% in 1996, an increase of over 90%. Twenty-seven percent of the strains we isolated showed a high-level of resistance to gentamicin.

In addition to showing 100% resistance to tetracycline,
P. mirabilis strains (Figure 3) showed high rates of resistance to ampicillin (58%), chloramphenicol (37%), the cephalosporins (about 30% to first and second generation drugs, and 10% to ceftazidime). A surprisingly high rate of resistance to azlocillin (26%) was also noted. As in E. coli, these resistance patterns are plasmid-mediated.

S. pneumoniae isolates were not numerous enough to make any general conclusions, though it is important to note that 33% of isolates were resistant to penicillin, a rate comparable to those registered in Spain, Hungary and France (6).

Nosocomial Pathogens
Enterobacter spp are typical nosocomial agents of infection. While they are intrinsically resistant to aminopenicillins and first generation cephalosporins, in the hospital setting, resistance to second and third generation cephalosporins may arise due to augmented chromosomal cephalosporinase. The strains we studied were highly resistant to tetracycline (about 70%) and chloramphenicol (about 25%). Resistance in nosocomial
E. cloacae to aminoglycosides is important to note because its increase serves as a predictor of nosocomial epidemia.

Klebsiella spp (Figure 4), another frequent nosocomial pathogen, typically obtains resistance through plasmid mediation after therapy with a new antibiotic (8,9). Such was the case in 30% of the strains we tested which showed resistance to ceftazidime (14% in 1995). Ten percent of stains isolated were resistant to aminoglycosides.

In the Intensive Care Unit (ICU) setting, and in immunocompromised patients,
Pseudomonas spp (Figure 5) play an important role in rates of infection. Forty-eight percent of strains we tested were resistant to gentamicin, 35% to ceftazidime, and 20% to imipenem. Furthermore, Acinetobacter spp, nonfermentative bacilli which also cause serious problems in the treatment of ICU patients (6) showed high resistance rates to aminoglycosides, ceftazidime and ciprofloxacin.

While the patterns of antibiotic use in both hospitals we studied differ from the national average, it appears that several resistance mechanisms are developing. These mechanisms are put into motion, in part, by inappropriate, misguided use of drugs. In 1996, for example, cefuroxime and cephalexin were the top two antibiotics prescribed at UHOT. Neither of these drugs are first or second-choice antimicrobials in the treatment of staphylococci infection (1,6,8), a leading cause of illness both inside and outside the hospital. These drugs are also often inappropriately used in cases of enterococcal infection, and may select for vancomycin-resistant organisms. Overuse and inappropriate use of ciprofloxacin at UHSIR, the top drug prescribed, also appears to be selecting for resistant enterococci, as well as for resistant
S. aureus.

The increasing antibiotic resistance rates found at UHOT and UHSIR highlight the need for implementing convenient methods for the epidemiologic tracking and control of nosocomial infections. We have been working with leading specialists to organize antibiotic committees to aid clinicians in making appropriate antimicrobial therapy choices.


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