KPC type [beta]-lactamase, rural Pennsylvania.

To the Editor: Rural counties have been defined as those lacking a metropolitan center that has a population >50,000 persons (1). Little is known about antimicrobial drug resistance in such communities in the United States. Stevenson and colleagues (2) recently evaluated antimicrobial drug-resistant gram-positive infections in rural hospitals in Idaho and Utah. These researchers found that both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci occurred in such settings, although some of the MRSA strains were probably community associated. Comparable studies on multidrug-resistant gram-negative infections have not been performed, to our knowledge.

Klebsiella pneumoniae producing a broad-spectrum [beta]-lactamase, KPC, has been described in tertiary care centers and other metropolitan hospitals in New York City. Examples have also been found in similar settings in Boston, New Jersey, Maryland, and North Carolina (3-5). The carbapenems (such as imipenem and meropenem) are typically the most active antimicrobial agents against the Enterobacteriaceae. The KPC [beta]-lactamases inactivate carbapenems and all other [beta]-lactam antimicrobial drugs. Unfortunately, bacteria producing the KPC type [beta]-lactamases are typically also resistant to trimethoprim/sulfamethoxazole, quinolones, and aminoglycosides, thereby making these pathogens truly multidrug resistant.

We describe a patient with KPC-producing 1<2. pneumoniae in a rural setting in central-west Pennsylvania. The case highlights the potential for multidrug-resistant gram-negative organisms to occur outside their previously recognized settings in large metropolitan centers.

The patient was a 76-year-old woman who lived alone, closely attended by her daughter, in a small, central Pennsylvania community, 95 miles from a metropolitan center with a population of >50,000. Her medical history included a seizure disorder, hypertension, osteoarthritis of the knees, obesity, osteoporosis, and total hysterectomy. A month before isolation of the KPC-producing K. pneumoniae, the patient had a 3-day hospital admission to a 200-bed hospital in the nearest metropolitan center (population 7,000) after a fall. She was discharged to a local nursing home for rehabilitation. She is not known to have visited or been hospitalized in New York, Philadelphia, or New Jersey, nor did she share a room with a patient known to have been hospitalized in these areas. She had no known animal contact. She had received trimethoprim/sulfamethoxazole and levofloxacin for treatment for urinary tract infections in the month before the KPC-producing strain was isolated. She was readmitted to the 200-bed hospital with pyelonephritis in August 2005. Cultures of urine grew K. pneumoniae; the organism was resistant to all [beta]-lactam antimicrobial drugs tested, including cefepime, ceftriaxone, piperacillin/tazobactam, imipenem, fluoroquinolones, trimethoprim/sulfamethoxazole, gentamicin, and tobramycin. The patient received therapy with amikacin in combination with cefepime, ertapenem, or tigecycline at different times over the following 4 weeks. Her symptoms improved, although her urine remained colonized with the multidrug-resistant K. pneumoniae. In October 2005, Clostridium difficile infection developed, accompanied by deep venous thrombosis and gastrointestinal bleeding, and the patient died. Multiple blood cultures collected before her death were negative, although the urine was persistently colonized with the multidrug-resistant K. pneumoniae.

The organism was referred to a research laboratory in a metropolitan center [approximately equal to] 100 miles away. Molecular analysis of the mechanisms of resistance was performed by using previously described methods (6). This analysis showed that the K. pneumoniae isolate produced the extended-spectrum [beta]-lactamase (ESBL) SHV-11 and the carbapenemase KPC-2.

Since community-associated ESBL-producing organisms have been described in Canada and Europe (7,8), acquisition or in vivo development of ESBL and KPC-producing strains could have occurred outside of the healthcare setting. More likely, the patient acquired her almost completely resistant gram-negative organism in the rural hospital or her local nursing home. To our knowledge, no other clinical isolates with the same antimicrobial phenotype have been seen in patients in either setting before or after the patient's admission. An unsuspected reservoir of patients colonized with antimicrobial drug--resistant gram-negative organisms may exist (9). Ideally, an epidemiologic investigation at both the hospital and nursing home would have been performed, but facilities for an investigation involving use of selective microbiologic media and assessment of gastrointestinal carriage of resistant organisms are not typically available in a rural setting. Indeed, most rural hospitals do not even use routine diagnostic tests for detecting resistant gram-negative organisms such as ESBL producers (10).

Although much attention has been focused on the progression of antimicrobial drug resistance in gram-positive organisms, the development of alternative antimicrobial agents such as linezolid and daptomycin may mitigate the disastrous scenario of complete resistance to all commercially available antimicrobial agents. However, few drugs are active against multidrug-resistant gram-negative pathogens, and enhanced measures are needed to prevent spread of these organisms. A greater understanding of the modes of spread and acquisition of these organisms is essential for effective control of this problem. We have reported just 1 case of infection with an almost completely resistant gram-negative organism. This case expands the known geographic spread of organisms with this resistance problem. This case also underscores the importance of studying the epidemiology of antimicrobial drug resistance in gram-negative organisms in the rural setting as well as in large metropolitan centers. Dissemination of knowledge regarding appropriate antimicrobial drug susceptibility testing for resistant organisms is also needed.

Jonathan Pope, * Jennifer Adams, ([dagger]) Yohei Doi, ([dagger]) Dora Szabo, ([dagger][double dagger]) and David L. Paterson ([dagger])

* Dubois Regional Medical Center, Dubois, Pennsylvania, USA; ([dagger]) University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA; and ([double dagger]) Semmelweis University, Budapest, Hungary

References

(1.) Ricketts TC, Johnson-Webb KD, Taylor P. Definitions of rural: a handbook for healthcare policy makers and researchers. Washington: Department of Health and Human Services; 1998.

(2.) Stevenson 1433, Searle K, Stoddard GJ, Samore M. Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci in rural communities, western United States. Emerg Infect Dis. 2005;11:895-903.

(3.) Bratu S, Mooty M, Nichani S, Landman D, Gullans C, Pettinato B, et al. Emergence of KPC-possessing Klebsiella pneumoniae in Brooklyn, New York: epidemiology and recommendations for detection. Antimicrob Agents Chemother. 2005 ;49:3018-20.

(4.) Woodford N, Tierno PM Jr, Young K, Tysall L, Palepou MF, Ward E, et al. Outbreak of Klebsiella pneumoniae producing a new carbapenem-hydrolyzing class A beta-lactamase, KPC-3, in a New York medical center. Antimicrob Agents Chemother. 2004;48:4793-9.

(5.) Yigit H, Queenan AM, Anderson G J, Domenench-Sanchez A, Biddle JW, Steward CD, et al. Novel carbapenem-hydrolyzing beta-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob Agents Chemother. 2001;45:1151-61.

(6.) Paterson DL, Hujer KM, Hujer AM, Yeiser B, Bonomo MD, Rice LB, et al. Extended-spectrum beta-lactamases in Klebsiella pneumoniae bloodstream isolates from seven countries: dominance and widespread prevalence of SHV- and CTX-M-type beta-lactamases. Antimicrob Agents Chemother. 2003;47:3554-60.

(7.) Rodriguez-Bano J, Navarro MD, Romero L, Martinez-Martinez L, Muniain MA, Perea EJ, et al. Epidemiology and clinical features of infections caused by extended-spectrum beta-lactamase-producing Escherichia coli in nonhospitalized patients. J Clin Microbiol. 2004;42:1089-94.

(8.) Pitout JD, Hanson ND, Church DL, Lanpland KB. Population-based laboratory surveillance for Escherichia coli-producing extended-spectrum beta-lactamases: importance of community isolates with [bla.sub.CTX]-M genes. Clin Infect Dis. 2004;38:1736-41.

(9.) Paterson DL, Singh N, Rihs JD, Squier C, Rihs BL, Muder RR. Control of an outbreak of infection due to extended-spectrum beta-lactamase-producing Escherichia coli in a liver transplantation unit. Clin Infect Dis. 2001;33:126-8.

(10.) Stevenson KB, Samore M, Barbera J, Moore JW, Hannah E, Houck P, et al. Detection of antimicrobial resistance by small rural hospital microbiology laboratories: comparison of survey responses with current NCCLS laboratory standards. Diagn Microbiol Infect Dis. 2003; 47:303-11.

Address for correspondence: David L. Paterson, Suite 3A, Falk Medical Bldg, 3601 5th Ave, Pittsburgh PA 15213, USA; email: [e-mail]

The opinions expressed by authors contributing to this journal do not necessarily reflect the opinions of the Centers for Disease Control and Prevention or the institutions with which the authors are affiliated.