Division of Epidemiology, Environmental and Occupational Health
Epidemiology Surveillance System

1995-1997 Report

Preface

Multiple antibiotic-resistant bacteria have been recognized as a serious threat to the nation's public health since the early 1990s. The tremendous therapeutic advantage afforded by antibiotics is jeopardized due to the increasing resistance of microbes. In an effort to develop a resource to measure antibiotic resistance in New Jersey and to provide a basis for the development of cost-effective measures to reduce further development of antibiotic resistance, the New Jersey Department of Health (NJDOH) launched a surveillance tool in 1991 to learn more about these organisms. A statewide hospital laboratory-based Epidemiology Surveillance System was established to monitor 1) methicillin-resistant Staphylococcus aureus (MRSA); 2) Gram-positive cocci resistant to vancomycin; 3) penicillin-resistant streptococci / enterococci; and 4) Gram-negative bacilli resistant to imipenem, amikacin, gentamicin, and tobramycin.

Methodology

A New Jersey Epidemiology Surveillance Record form is submitted monthly by each acute care hospital in New Jersey (Attachment 1). These forms are checked for completeness upon receipt by staff in the NJDOH Infectious and Zoonotic Diseases Program. Follow-up telephone calls are made to ensure that all forms are submitted each month and that all isolates are sent to the NJDOH Public Health and Environmental Laboratories.

The number of participating hospitals was 94, 94, and 89, respectively, in 1995, 1996 and 1997. This number decreased because of hospital closures and laboratory consolidations.

In addition to updating the overall number and trend of each category of infection provided by the previous report, this report also includes the rates and the distribution of isolates by facility and by county as well as the drug-resistance profile and the trend of resistance patterns in each class of organism. Rates by facility are normalized by number of occupied beds in each facility each year, while rates by county are normalized by the resident population in each county each year. Please be advised that the marginal error in the 1996 data could be as high as 10 percent (estimated) due largely to unidentified mistakes in data entry.

Summary

The 1995 to 1997 data collected by the New Jersey Epidemiology Surveillance System indicates that by 1997 the vancomycin-resistant enterococci (VRE) and penicillin-resistant Streptococcus pneumoniae isolates have increased five-fold since the inception of the system in 1992. National data also display a substantial increase of these isolates during the same period1,2. Trending of increasing multiple-antibiotic resistance of these organisms has further compounded the problem. MRSA have increased steadily during the survey period in New Jersey which parallels the national trend1. Among Gram-negative bacilli, a moderate increase was observed in amikacin resistance, while resistance to imipenem has increased only slightly. Although, no direct comparison of New Jersey figures with national resistance trends is available, multiple resistant Gram-negative bacilli are classified as current and future crisis in the United States hospitals3.

MRSA Isolates in New Jersey Hospitals

S. aureus remains the leading organism causing bacteremia in the hospital setting in the United States and Canada4. The rate of methicillin resistance in this organism has increased from 20 to 25 percent in 1990 to 25 to 45 percent in 1997 nationwide2. The bar chart in Exhibit 1 compares the number of methicillin-resistant S. aureus reported by year during the 1991 to 1997 period in New Jersey. The total number of inpatient isolates remained relatively constant in 1995 and 1996, however an increase in 1997 was observed. Of the 17,299 MRSA isolates reported in 1997, 33% were from wound cultures, 27% from sputum cultures, 13% from blood cultures, 12% from urine cultures and 15% from cultures of other body sites. Exhibit 2 displays the number of reported MRSA isolates per 100 occupied beds per month in 1995, 1996, and 1997. Facilities were ranked by rate in descending order. The State total, based on the normalized MRSA rate, shows an increasing trend in this rate between 1995 and 1997.

Antibiotic-Resistant Bacteria B Bloodstream Infections in New Jersey Hospitals

A total of 686, 731, and 872 antibiotic-resistant bacteria isolated from blood cultures were reported in 1995, 1996, and 1997, respectively. The frequency of antibiotic-resistant blood isolates in each facility, ranked in descending order by the number of isolates per 100 occupied beds, is illustrated in Exhibit 3. The State total shows an increasing trend in this rate between 1995 and 1997. Distribution of these isolates by county is highlighted in Exhibit 4, in which each county's rate is normalized by its resident population.

Vancomycin-Resistant Gram-Positive Cocci in New Jersey Hospitals

Enterococci have been documented to be the fourth most prevalent isolates from blood cultures in United States and Canada4. Of these, 69.9 percent represent true bacteremias, 76.9 percent are nosocomially acquired infections, and 13.1 percent are associated with mortality5. The occurrence of VRE nationwide has increased from less than 1 percent in 1990 to 6 percent in 1992, 8 percent in 1994, 16 to 17 percent in 1996, and 18 percent in 19972. The occurrence of new patterns of resistance in clinical isolates, such as vancomycin intermediate-resistant S. aureus6 and Staphylococcus epidermidis7, vancomycin heterogeneous-resistant S. aureus8 and coagulase-negative staphylococci9, and vancomycin-tolerant S. pneumoniae10 has been documented recently. For New Jersey, Exhibit 5 summarized the variety and number of Gram-positive cocci, collected from 1992 to 1997 that harbor vancomycin resistance. The majority of these specimens (ranging from 95.02% in 1993 to 98.75 % in 1997) belong to the genus Enterococcus. Several vancomycin-resistant isolates of Streptococcus and Staphylococcus were reported; however, confirmation of these reports was not accomplished. Specimens from such isolates should be sent to the NJDOH laboratory for confirmation. The trend of VRE blood isolates from 1992 to 1997 is presented in Exhibit 6. VRE increased nearly five-fold during this period, from an average of 8.32 isolates per month in Jan.1992 to 41.94 isolates per month in Dec. 1997. Exhibit 7 depicts the rate and the distribution of VRE by county from 1995 to 1997. Counties containing only one hospital were aggregated with a neighboring county so that no hospital would have its specific rates identified. Exhibit 8 summarizes the drug resistance profile of major VRE groups, collected from 1995 to 1997. Enterococcus faecium is the most frequent organism and in 1997 it carried a high level of resistance to penicillin (98.1 percent), oxacillin (100 percent), ampicillin (97.5 percent), imipenem (86.6 percent), erythromycin (95 percent), ciprofloxacin (98.1 percent), ofloxacin (100 percent), high concentration gentamicin (73.8 percent), and high concentration streptomycin (88.5 percent). An increasing trend of resistance in tetracycline and trimethoprim/sulfamethoxazole was also observed in the 1997 collection of E. faecium. In comparison, the reported national rates of antibiotic resistance in Enterococcus not limited to vancomycin-resistant isolates are: ampicillin/penicillin 25.7/27.5 percent, ciprofloxacin 66.1 percent, chloramphenicol 17.2 percent, tetracycline 66.4 percent, teicoplanin 12.6 percent, vancomycin 17.7 percent, high concentration gentamicin 33.3 percent, and high concentration streptomycin 43.3 percent1.

Penicillin-Resistant Streptococci / Enterococci in New Jersey Hospitals

S. pneumoniae has been documented to be the sixth most prevalent organism isolated from blood cultures in the United States, while viridans streptococci ranks eleventh4. The blood isolates of S. pneumoniae represent 100 percent true bacteremia, are mostly community-acquired (91.2 percent), and are associated with a 17.6 percent mortality rate5. The national rate of pneumococcal resistance to penicillin has increased from 4 percent in 1990 to 7 percent in 1992, 16 percent in 1994, 24 to 27 percent in 1996, and 31 to 42 percent in 19972. Exhibit 9 lists the variety and the number of penicillin-resistant streptococci and enterococci reported from 1992 to 1997 from New Jersey hospitals. The most frequently reported organism is E. faecium, followed by S. pneumoniae. Exhibit 10 shows an estimated 250 percent increase in the incidence of penicillin-resistant streptococci and enterococci, from 13.69 isolates per month in Jan. 1992 to 34.54 isolates per month in Dec. 1997. The rate and the distribution of these isolates by county are demonstrated in Exhibit 11. Exhibits 12 and 13 show the frequency trend and distribution by county of penicillin-resistant S. pneumoniae, between 1992 and 1997. A substantial increase of 550 percent in penicillin-resistant S. pneumoniae during this period is estimated. Exhibit 14 summarizes the drug resistance profile in major penicillin-resistant streptococci and enterococci groups. A high proportion of E. faecium isolates have additional resistance to ampicillin, gentamicin, streptomycin, erythromycin, ciprofloxacin and vancomycin. Vancomycin is effective against most penicillin-resistant S. pneumoniae isolates. However, increasing resistance in penicillin-resistant S. pneumoniae to ampicillin and oxacillin (100 percent), cefotaxime (25 percent), ceftriaxone (19.5 percent), erythromycin (28.6 percent), chloramphenicol (22.6 percent), clindamycin (28.6 percent), tetracycline (39.3 percent), and trimethoprim/sulfamethoxazole (75 percent) was observed in the 1997 collection. For comparison, the reported national rates of resistance among S. pneumoniae not limited to penicillin-resistant isolates are: ampicillin 15.6 percent, penicillin 41 percent, amoxicillin-clavulanate 16.6 percent, cefuroxime 20.5 percent, cefotaxime/ceftriaxone 13.2 percent, cefepime 16.6 percent, erythromycin 11.9 percent, clindamycin 4 percent, chloramphenical 3.5 percent, rifampin 0.5 percent, tetracycline 10.9 percent, vancomycin 0 percent, and trimethoprim/sulfamethoxazole 25.2 percent4.

Amikacin-Resistant Gram-Negative Bacilli in New Jersey Hospitals

Gram-negative bacilli are also important pathogens in bloodstream infections. Among them, Klebsiella spp. ranked fifth in frequency, Pseudomonas aeruginosa ranked seventh, Proteus mirabilis ranked tenth, Acinetobacter spp. ranked twelfth, Serratia spp. ranked thirteen, Citrobacter spp. ranked fourteen, Stenotrophomonas maltophilia ranked fifteen in a national study4. Exhibit 15 displays the variety and the number of amikacin-resistant Gram-negative bacilli reported from 1992 to 1997 in New Jersey hospitals. The most frequently reported Gram-negative organisms, other than those from the Enterobacteriaceae family, are S. maltophilia, Acinetobacter baumannii, P. aeruginosa, Alcaligenes xylosoxidans and Burkholderia cepacia. Species within the Enterobacteriaceae family accounted for 22.64% of the total collection in 1997. Among them, Klebsiella pneumoniae was the predominant organism. Exhibits 16 and 17 illustrate the six-year trend and the distribution of these isolates by county, respectively. A moderate increase, from an average of 4.81 isolates per month in Jan. 1992 to 8.72 isolates per month in Dec. 1997 is demonstrated in Exhibit 16.

Imipenem-Resistant Gram-Negative Bacilli in New Jersey Hospitals

Exhibit 18 depicts the number and variety of imipenem-resistant Gram-negative bacilli reported from 1992 to 1997. The total number within this collection increased slightly during these years as demonstrated in Exhibit 19. However, a decreasing trend is found in the number of Enterobacteriaceae. The decline in the number of P. mirabilis is especially evident. P. aeruginosa and S. maltophilia are the most frequently reported isolates. Exhibit 20 depicts the rate and the distribution of these organisms by county.

Drug Resistance Profile in Gram-Negative Bacilli in New Jersey Hospitals

Exhibit 21 displays the drug resistance profile in major Enterobacteriaceae blood isolates. A high percentage of resistance to penicillins and aminoglycosides as well as the expanded-spectrum beta-lactam antibiotics in K. pneumoniae was observed. The resistance to amikacin and trimethoprim/sulfamethoxazole also tend to increase by time. A high frequency of imipenem resistance is observed in P. mirabilis, and Serratia marcescens, compares to K. pneumoniae.

Exhibit 22 demonstrates the drug resistance profile in major Gram-negative bacilli that do not belong to Enterobacteriaceae. Imipenem resistance is predominant in S. maltophilia, P. aeruginosa, B. cepacia, and Flavobacteriumn meningosepticum. High frequency of aminoglycosides resistance is also observed in S. maltophilia, B. cepacia, F. meningosepticum, and A. baumannii. It is noteworthy that the trend of resistance to trimethoprim/sulfamethoxazole, the most active agent against S. maltophilia, increased sharply between 1995 and 1997.

References

  1. Fridkin SK, and Gaynes RP. (1999) Antimicrobial resistance in intensive care units. Clin Chest Med 20:303-316.
  2. Jones RN, Low DE, and Pfaller MA. (1999) Epidemiologic trends in nosocomial and community-acquired infections due to antibiotic-resistant Gram-positive bacteria: the role of streptogramins and other newer compounds. Diagn Microbiol Infect Dis 33:101-112.
  3. File TM, Jr. (1999) Overview of Resistance in the 1990s. Chest 115:3S-8S.
  4. Pfaller MA, Jones RN, Doern BF, Kugler, K, and the SENTRY Participants Group. (1998) Bacterial Pathogens isolated from patients with blood stream infection: frequencies of occurrence and antimicrobial susceptibility patterns from the SENTRY antimicrobial Surveillance Program (United States and Canada, 1997). Antimicrob Agents Chemother 42:1762-1770.
  5. Weinstein MP, Towns ML, Quartey SM, et al. (1997) The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults. Clin Infect Dis 24:584-602.
  6. Smith TL, Pearson ML, Wilcox KR, et al. for the Glycopeptide-Intermediate Staphylococcus aureus Working Group*. (1999) Emergence of vancomycin resistance in Staphylococcus aureus. N Engl J Med 340:493-501.
  7. Garrett DO, Jochimsen E, Murfitt K, et al. (1999) The emergence of decreased susceptibility to vancomycin in Staphylococcus epidermidis. Infect Control Hosp Epidemiol 20:167-170.
  8. Hiramatsu K, Aritaka N, Hanaki H, et al. (1997) Dissemination in Japanese hospitals of strains of Staphylococcus aureus heterogeneously resistant to vancomycin. Lancet 350:1670-1673.
  9. Sieradzki K, Villari P, Tomasz A. (1998) Decreased susceptibilities to teicoplanin and vancomycin among coagulase-negative methicillin-resistant clinical isolates of staphylococci. Antimicrob Agents Chemother 42:100-107.
  10. Novak R, Henriques B, Charpentier E, Normark S, Tuomanen E. (1999) Emergence of vancomycin tolerance in Streptococcus pneumoniae. Nature 399:590-593.

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