Antimicrobial Resistance in Common Bacterial Pathogens causing Community-Acquired Pneumonia

Diane C. Halstead, Ph.D. and Joseph D.C. Yao, M.D., Infectious Disease Laboratories, Baptist Medical Center, and Division of Infectious Diseases, Mayo Clinic Jacksonville, Florida

In order to achieve optimum outcomes from these practice guidelines, knowledge of prevalent antibiotic resistance profiles of the important bacterial pathogens causing CAP is essential. Of even greater benefit would be the availability of a "community-wide antibiogram" (CWA) that represents a composite of the susceptibilities of common pathogens to various classes of antimicrobial agents. The antibiogram could be used to select the appropriate antibiotics for the treatment of CAP.

However, susceptibility data on Moraxella catarrhalis, Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella pneumophila would need to be gleaned from the literature, since antimicrobial susceptibility testing cannot be performed routinely in most clinical microbiology laboratories and there are no laboratory standards for interpretation of susceptibility results. In this article, we present the antimicrobial susceptibility profiles of important bacterial pathogens associated with CAP at hospitals in the Jacksonville area. Our susceptibility patterns over the 6-year period from 1995 to 2000 are also compared with available national data.

Effective surveillance of antibiotic-resistant organisms is a key component in forming a strategy to control the development and spread of antimicrobial resistance. The CWA for Jacksonville area hospitals was examined and developed in 3 aspects: 1) overall extent of antibiotic resistance in our community; 2) significant differences in antibiotic susceptibilities among the hospitals; and 3) change in susceptibilities over a 6-year period from 1995 to 2000. The data presented consist of results collected from both inpatient and outpatient populations from eight hospitals in the Jacksonville area, including one pediatric facility. A letter of the alphabet identifies each hospital. Although the susceptibility test methods varied among institutions and among different organisms tested, the National Committee on Clinical Laboratory Standards (NCCLS) were used to interpret inhibitory zone sizes and minimum inhibitory concentrations (MICs).^{5, 6}

b-Lactam drug resistance in Streptococcus pneumoniae is caused by altered penicillin-binding proteins (PBPs) in the cell wall of resistant organisms. The altered PBPs have reduced affinity for penicillins or cephalosporins that must bind to PBP target sites to exert their inhibitory effects. In our current retrospective review of pneumococcal susceptibility results, most hospital laboratories screened for resistance to penicillin by using an oxacillin disk. All resistant isolates were then confirmed by performing a MIC method such as E-test or broth dilution. However, an inherent delay in reporting susceptibility results occurred using this testing approach, as penicillin resistance became more prevalent and more confirmatory tests were required. With the increasing prevalence of resistance evident in Jacksonville area, many microbiology laboratories have now chosen a MIC method as the first susceptibility test for pneumococci. Pneumococcal isolates are defined as susceptible, intermediate susceptible, or resistant to penicillin by having MICs of < 0.1 mg/mL, 0.1 to 1 mg/mL, or > 1 mg/mL, respectively.⁶

The prevalence of S. pneumoniae non-susceptible to penicillin (MIC ³ 0.1 mg/mL) at various hospitals in the Jacksonville area is shown in Figure 1.

We did not attempt to separate inpatient and outpatient data, since other investigators have found that the difference in susceptibilities between the two groups were within 5% of one another for each antimicrobial tested.⁷ The average percentage of penicillin-susceptible strains (with total number of isolates tested in parenthesis) recovered in Jacksonville for each year from 1995 to 2000 was 67% (180 isolates), 58% (271), 40% (351), 42% (331), 46% (539), and 47% (366), respectively. Over a 6-year period, penicillin susceptibility decreased 20% from 67% to 47%. In contrast, national data collected during the 1998-1999 and 1999-2000 respiratory seasons through the TRUST IV study, one of the largest multicenter surveillance programs in the U.S., showed susceptible rates compared to those in Jacksonville, i.e., 66% and 67% susceptible, respectively.⁸ Three hospitals in Jacksonville exhibited a significant decrease in pneumococcal susceptibility from 72% to 33% (hospital C), 60% to 38% (hospital E) and 71% to 58% (hospital H) during the 6 years. In contrast, hospital B which serves a pediatric population, has a consistent record of isolating S. pneumoniae non-susceptible to penicillin at annual prevalence ranging between 60% and 77%. The highest percentage of high-level penicillin resistance (> 1 mg/mL) in Jacksonville was seen in an exclusively pediatric population, i.e., 52% versus a low of 10% to 37% in the other hospitals serving a predominantly adult population. These findings are consistent with the TRUST IV data that revealed prevalence rates of 43.6% in those <15 yr old, 31.9% between 15 and 65 yr old, and 30.9% in those >65 yr old.⁸ When data were analyzed by geographic location in the TRUST study, the South Atlantic region had the highest rate of penicillin resistance in the country (24.8%).

Since recent recommendations for empiric therapy for moderately to critically ill patients hospitalized with pneumonia include a parenteral b-lactam drug, such as cefotaxime or ceftriaxone, and a macrolide or a fluoroquinolone alone, we collated the data for these four drugs. The overall prevalence rates (with total number of isolates tested in parenthesis) of cefotaxime-susceptible pneumococcal isolates in Jacksonville were 70% (22) in 1995, 78% (224) in 1996, 65% (306) in 1997, 77% (293) in 1998, 65% (537) in 1999, and 70% (325) in 2000. Over the 6-year period, susceptibility data on both cefotaxime and ceftriaxone have changed from 83% to 78% and 77% to 83% respectively at hospital A, from 56% to 42% and 65% to 54% respectively in hospital B, and from 81% to 90% and 80% to 98% respectively in hospital H (Table 1).

Of note is the finding that S. pneumoniae strains isolated at the pediatric hospital (hospital B) are more resistant to cefotaxime and ceftriaxone during the six years of surveillance, in comparison to hospitals A, C, D, E and H that serve predominantly the adult population. This observation is consistent with the findings reported in national surveillance data indicating higher prevalence of cephalosporin resistance among pneumococcal strains resistant to penicillin.^7-9 Resistance to erythromycin has increased in S. pneumoniae among the four hospitals in Jacksonville that reported susceptibility to erythromycin (Table 2).

In particular, susceptibility decreased significantly from 64% to 36% in hospital B (pediatric hospital) and from 94% to 25% (hospital C) over the 6-year period. Overall, erythromycin susceptibility rate declined from 80% in 1995 to 47% in 2000, in contrast to the stable rates of about 22% found in various U.S. surveillance studies.^7-9 However, susceptibility patterns for clindamycin at the same four hospitals were stable with overall rates of 89% in 1995 and 90% in 2000, similar to national surveillance reports. With data available from 1995 to 2000, susceptibility to clindamycin has remained relatively stable for hospitals A (from 100% to 96%) and B (from 77% to 84%).

Resistance to fluoroquinolones such as levofloxacin is due to mutational alterations in two bacterial enzymes, DNA gyrase and topoisomerase IV, which are targets for the drug. In Jacksonville, the overall susceptibility rates (with total number of isolates tested in parenthesis) for levofloxacin in S. pneumoniae 99% (240) in 1998, 100% (541) in 1999, and 99% (331) in 2000. These rates are consistent with national data from the SENTRY and TRUST studies (0.2% to 0.8 % overall resistance rates for levofloxacin).^8-11

Ampicillin-resistant H. influenzae was first reported in the United States in 1974. The majority of H. influenzae strains that are resistant to ampicillin and amoxicillin produce a plasmid-mediated TEM-type b-lactamase or more rarely, a second type of b-lactamase called ROB-1. These isolates are susceptible to combinations of b-lactam / b-lactam inhibitors, such as ampicillin-sulbactam and amoxicillin-clavulanate. However, rare isolates of H. influenzae have been found since 1980 to be resistant to ampicillin as a result of chromosomal-mediated alteration of PBPs or altered permeability of bacterial cell membrane. These strains are also resistant to b-lactam / b-lactam inhibitor combinations of antibiotics. In most instances, a direct test for b-lactamase (Cefinase© disk test) can rapidly detect resistance to ampicillin and amoxicillin, but only in those isolates that are resistant by production of b-lactamases. Many clinical laboratories limit full susceptibility testing of H. influenzae to those strains isolated from sterile body sites (e.g. blood, CSF, joint fluid) and only perform the rapid, direct b-lactamase test on isolates from other body sites (sputum, wound). Prevalence of H. influenzae isolates that are ampicillin-resistant or b-lactamase-positive in Jacksonville have gradually increased from 34% in 1995 to 47% in 1999. In contrast, 31% to 33% of the H. influenzae isolates reported in several national surveillance studies were b-lactamase-positive.

CAP caused by Staphylococcus aureus is more prevalent in the elderly and in patients with pneumonia secondary to influenza infection. For the six years of antimicrobial surveillance in Jacksonville, overall prevalence of methicillin-resistant S. aureus (MRSA), as determined by resistance to oxacillin in clinical laboratories, has increased steadily from 23% in 1995 to 48% in 2000 (Tables 3, 4).

Although our surveillance data reflect combined prevalence in both community and nosocomial settings, the rates for Jacksonville are slightly higher than those reported in recent national surveillance studies (~ 40%).^14,15 Interestingly, MRSA was relatively less prevalent in the pediatric hospital (hospital B), with only 3% in 1995 and 14% in 2000, in contrast to recent trends of increasing prevalence of MRSA among community-acquired and nosocomial strains isolated at tertiary care centers.^16-18

Knowing how to use antibiotics appropriately has become even more important in light of increasing antimicrobial resistance in our community. Both healthcare providers and patients have responsibilities concerning the appropriate use of antibiotics. Given the fact that most antibiotics are prescribed empirically and in the outpatient settings, prescribers should familiarize themselves with the prevalent antimicrobial resistance patterns in their community. We hope that the data presented in this survey report will enhance the efforts of educating healthcare providers in the appropriate use of antibiotics in the treatment of CAP.

References

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18. Hussain FM, Boyle-Vavra S, Bethel CD, Daum RS. Current trends in community-acquired methicillin-resistant Staphylococcus aureus at a tertiary care pediatric facility. Pediatr Infect Dis J. 2000; 19:1163-1166.

April, 2001/ Jacksonville Medicine

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