Volume 13, Number 11—November 2007
Human Salmonella and Concurrent Decreased Susceptibility to Quinolones and Extended-Spectrum Cephalosporins
The National Antimicrobial Resistance Monitoring System monitors susceptibility among Enterobacteriaceae in humans in the United States. We studied isolates exhibiting decreased susceptibility to quinolones (nalidixic acid MIC >32 µg/mL or ciprofloxacin MIC >0.12 µg/mL) and extended-spectrum cephalosporins (ceftiofur or ceftriaxone MIC >2 µg/mL) during 1996–2004. Of non-Typhi Salmonella, 0.19% (27/14,043) met these criteria: 11 Senftenberg; 6 Typhimurium; 3 Newport; 2 Enteridis; and 1 each Agona, Haifa, Mbandaka, Saintpaul, and Uganda. Twenty-six isolates had gyrA mutations (11 at codon 83 only, 3 at codon 87 only, 12 at both). All Senftenberg isolates had parC mutations (S80I and T57S); 6 others had the T57S mutation. The Mbandaka isolate contained qnrB2. Eight isolates contained blaCMY-2; 1 Senftenberg contained blaCMY-23. One Senftenberg and 1Typhimurium isolate contained blaSHV-12; the Mbandaka isolate contained blaSHV-30. Nine Senftenberg isolates contained blaOXA-1; 1 contained blaOXA-9. Further studies should address patient outcomes, risk factors, and resistance dissemination prevention strategies.
Although antimicrobial agents are not indicated for uncomplicated Salmonella infections, fluoroquinolones and extended-spectrum cephalosporins are potentially life-saving treatments for extraintestinal infections (1). The National Antimicrobial Resistance Monitoring System (NARMS) has monitored antimicrobial drug resistance among enteric pathogens since 1996. NARMS has documented decreased susceptibility to each of these drug classes, in most instances among separate serotypes (2). Historically, decreased susceptibility to fluoroquinolones, which can be monitored by tracking resistance to nalidixic acid, has been noted among Salmonella serotypes (ser.) Typhi, Senftenberg, and Virchow (2,3). More recently, decreased susceptibility to fluoroquinolones has been noted among Salmonella ser. Enteritidis (4). Decreased fluoroquinolone susceptibility has also been seen among nalidixic acid–susceptible isolates (5). Extended-spectrum cephalosporin resistance was noted among 15 non-Typhi Salmonella NARMS isolates (including 12 ser. Typhimurium) during 1996–1998 (6). In all instances, extended-spectrum cephalosporin resistance was the result of blaCMY-2, a class C plasmid-encoded ampC gene (7). In addition to conferring resistance or decreased susceptibility to extended-spectrum cephalosporins such as ceftiofur and ceftriaxone, this gene also confers resistance to ampicillin (AMP), amoxillin-clavulanate, cephalothin, and cefoxitin. This AmpC resistance phenotype has been seen in strains of Salmonella ser. Newport along with resistance to other drugs including chloramphenicol, streptomycin, sulfamethoxazole, and tetracycline. This MDRAmpC strain rose from 1% (1/77) of Salmonella ser. Newport submissions in 1998 to 25% (31/124) in 2001 (4). CMY β-lactamases are largely responsible for extended-spectrum cephalosporin resistance among Salmonella ser. Newport, Typhimurium, and others isolated in North America (6,8).
Coresistance to fluoroquinolones and extended-spectrum cephalosporins would limit therapeutic options for Salmonella infections. Decreased susceptibility to both drug classes was identified in Thailand in 1993 (ser. Anatum, Derby, Enteritidis, Typhimurium, Weltevreden, and I 4,5,12:i:-) (9), the United Kingdom in 1998 (ser. Senftenberg, Typhimurium, and Virchow) (10), Belgium as early as 2001 (ser. Virchow) (11), India in 2002 (ser. Typhi) (12), the United States in 2002 (ser. Mbandaka) (13), France in 2003 (11), and Taiwan in 2004 (ser. Choleraesuis, Cairo, and Kaduna) (14). In the United States, 27 (4.6%) of 588 Salmonella ser. Typhimurium isolates (clinical and slaughter) obtained from food animals in 1999 were resistant to ceftiofur and nalidixic acid: 22 (81%) from turkeys, 4 (15%) from horses, and 1 (4%) from cattle (15).
To understand coresistance to both antimicrobial classes among Salmonella isolates obtained from humans in the United States, we studied the NARMS human collection from 1996 through 2004, looking for decreased susceptibility to quinolones and extended-spectrum cephalosporins. Information for some of the isolates has been presented elsewhere (3,13,16–18). We present the molecular epidemiology of this phenotype and mechanisms responsible for its decreased susceptibility.
Isolates and Antimicrobial Drug Susceptibility Testing
NARMS-participating state and local public health laboratories submitted non-Typhi Salmonella isolates to the Centers for Disease Control and Prevention (CDC) for antimicrobial susceptibility testing: every 10th isolate from 1996 through 2002 and every 20th isolate from 2003 to present. Serotypes were determined by the submitting laboratory and, for this study, were confirmed by the CDC National Salmonella Reference Laboratory according to the Kaufmann-White scheme as described (19). MICs were determined by using broth microdilution (Sensititre, Westlake, OH, USA). Isolates exhibiting an amikacin MIC >4 μg/mL were confirmed by Etest (ABBiodisk, Piscataway, NJ, USA). Criteria for decreased susceptibility to quinolones and extended-spectrum cephalosporins were as follows: MIC >32 μg/mL for nalidixic acid or >0.12 μg/mL for ciprofloxacin and >2 μg/mL for ceftiofur or ceftriaxone. Susceptibility testing was performed according to manufacturer’s instructions by using control strains Escherichia coli ATCC25922 and ATCC35218, and Klebsiella pneumoniae ATCC700603 (for extended-spectrum β-lactamase [ESBL] confirmation only). When available, Clinical Laboratory Standards Institute (CLSI) guidelines were used for interpretation (20).
Isoelectric Focusing for β-Lactamases
The methods of Rasheed et al. were used with modification (21). Three-hour trypticase soy broth cultures (grown at 37°C with shaking at 300 rpm) were pelleted, resuspended in 0.2% sodium acetate to 5% of original culture volume, and freeze-thawed 4 times (dry ice/ethanol bath and 37°C water bath). Preparations were diluted 2-fold with distilled water and swirled occasionally on ice for 30 min. Supernatants were collected after centrifugation (30 min at 20,200× g), and 3–5-µL aliquots were resolved for 1.5 h on Ampholine PAGplate polyacrylamide gels, pH 3.5–9.5 (APBiotech, Piscataway, NJ, USA). Gels were stained with nitrocefin (500 μg/mL; Becton Dickinson, Franklin Lakes, NJ, USA). Isoelectric points (pIs) were estimated by comparison with the following standard β-lactamases: TEM-12 (pI 5.25), KPC-2 (pI 6.7), SHV-3 (pI 7.0), SHV-18 (pI 7.8), and MIR-1 (pI 8.4).
PCR Detection of Antimicrobial Drug Resistance Genes
Presence of qnr genes was determined by using PCR with primers QP1 and QP2 for qnrA (22), FQ1 and FQ2 for qnrB (23), and 5′-ATGGAAACCTACAATCATAC-3′ and 5′-AAAAACACCTCGACTTAAGT-3′ for qnrS. The qnrB allele was determined by amplification and sequencing with primers FQ1 and FQ2. Screening for aac(6′)-Ib-cr was performed as described (24). Primer pairs used for amplification of β-lactamase genes were: blaCMY (5′-ATGATGAAAAAATCGTTATGC-3′) and (5′-TTGCAGCTTTTCAAGAATGCGC-3′) (25); blaOXA-1 (5′-AATGGCACCAGATTCAACTT-3′) and 5′-CTTGGCTTTTATGCTTGATG-3′) (26); blaTEM (5′-TTCTTGAAGACGAAAGGGC-3′) and (5′-ACGCTCAGTGGAACGAAAAC-3′) (27); and blaSHV (5′-GGTTATGCGTTATATTCGCC-3′) and (5′-TTAGCGTTGCCAGTGCTC-3′) (28) or at Lahey (5′-GCCGGGTTATTCTTATTTGTC-3′) and (5′-TCTTTCCGATGCCGCCGCCAG-3′) (29). blaCTX-M genes were screened by using a multiplex PCR assay (30).
Full-length sequences were obtained for β-lactamase genes. A 255-bp region covering the quinolone-resistant determining region (QRDR) of gyrA (Met52 to Leu137) was amplified by using primers gyrA1: 5′-CATGAACGTATTGGGCAATG-3′ and gyrA2: 5′-AGATCGGCCATCAGTTCGTG-3′. QRDRs of gyrB, parC, and parE were amplified and sequenced by using previously described primers (31), except primers parCF (5′-ATCGTGCGTTGCCGTTTAT-3′) and parCR (5′-GCCGCTTTCGCCACTTC-3′) were used to enhance coverage of parC. Amplicons were sequenced by using ABI Big-Dye 3.1 chemistry and ABI 3730XL automated DNA sequencers (PE Biosystems, Foster City, CA, USA). Analysis was performed by using BioEdit (www.mbio.ncsu.edu/BioEdit/bioedit.htmL) or SeqMan software (DNAStar, Madison, WI, USA). QRDR sequences of gyrA, gyrB, parC, and parE were compared with those of Salmonella ser. Typhimurium LT2 (GenBank accession nos. AE008801, AE008878, AE008846, and AE008846, respectively).
Pulsed-Field Gel Electrophoresis (PFGE)
PFGE was performed as previously described (32). Isolates that produced indistinguishable patterns with XbaI (Roche Molecular Biochemicals, Indianapolis, IN, USA) were restricted with BlnI. Patterns were analyzed by using the BioNumerics version 4.0 software (Applied Maths, Sint-Martens-Latem, Belgium) and compared by unweighted pair group method with averages by using the Dice coefficient with a 1.5% band position tolerance window. The DNA sequence and deduced amino acid sequence for the Salmonella ser. Senftenberg blaCMY-23 gene were assigned GenBank accession no. DQ463751.
Decreased susceptibility to quinolones and extended-spectrum cephalosporins was first noted in NARMS data in 1997 and represented 0.19% (27/14,043) of non-Typhi Salmonella from 1996 through 2004 (Table 1). Salmonella ser. Senftenberg was the most frequent serotype (n = 11), followed by Typhimurium (n = 6), Newport (n = 3), and Enteritidis (n = 2). The phenotype was found in 9 different serotypes (Table 2).
PFGE comparison by XbaI and, if applicable, BlnI restriction showed that 15/27 Salmonella isolates differed by >1 band. No indistinguishable patterns among different Salmonella serotypes were identified. Of the 3 ser. Newport isolates tested, 2 (AM15201 and AM21465) had indistinguishable XbaI patterns but different BlnI patterns (87.51% similarity). The 2 Enteritidis isolates (AM09124 and AM15266) were indistinguishable by both enzymes. Of the 11 ser. Senftenberg isolates, 5 exhibited unique XbaI PFGE patterns, while the remaining 6 were separated into 2 groups with indistinguishable XbaI PFGE patterns (group 1: AM06960, AM08081, AM16094, and AM19422; group 2: AM20227 and AM20256). BlnI restriction demonstrated that AM19422 differed from the other group 1 isolates by a single band difference (97.44% similarity). PFGE results for some of the Senftenberg isolates are described elsewhere (16,18). All Typhimurium isolates exhibited unique XbaI PFGE patterns (77%–93% similarity).
Antimicrobial drug susceptibility results are presented in Table 3. For nalidixic acid, 25 isolates exhibited an MIC >32 μg/mL, and 2 (Mbandaka and Newport) had an MIC of 16 μg/mL. For ciprofloxacin, MICs of 0.12–0.5 μg/mL were found for all isolates except the 11 Senftenberg, for which the MIC was >4 μg/mL. For ceftiofur, 14 isolates exhibited resistance (MIC >8 μg/mL). For ceftriaxone, 2 isolates exhibited resistance according to the current CLSI breakpoint (64 μg/mL), and 7 exhibited intermediate resistance (MIC 16 or 32 μg/mL). Three isolates (Mbandaka, Senftenberg, and Typhimurium) exhibited an ESBL phenotype according to ceftazidime and cefotaxime MIC alone and with clavulanate. Seven isolates exhibited the MDRAmpC phenotype, including 1 Agona, 2 Newport, 3 Typhimurium, and 1 Uganda. According to current CLSI guidelines, 1 isolate (ser. Senftenberg) was fully resistant to ciprofloxacin, ceftriaxone, ceftazidime, and cefotaxime.
The mechanisms responsible for resistance and decreased susceptibility are shown in Table 4. Some mechanisms for some of the isolates are presented elsewhere (3,17,18). At least 1 gyrA mutation was found in 26 of 27 isolates. A gyrA mutation at codon 83 only was found for 11 isolates; a mutation at codon 87 only was found for 3; mutations at both codons were found for 12. No functional mutations were detected in gyrB or parE genes. All Senftenberg isolates had parC mutations (S80I and T57S), and 6 other isolates had the T57S mutation. In addition to the T57S mutation in parC, the Mbandaka isolate contained a plasmid-mediated qnrB2 gene and has been described (13). Four isolates contained aac(6′)-Ib, but none contained the ciprofloxacin-modifying aac(6′)-Ib-cr variant.
Nine AmpC phenotype isolates produced β-lactamase with a pI >8.4 (Table 4); 8 contained blaCMY-2, but the Senftenberg strain contained a blaCMY-23 gene (GenBank accession no. DQ463751) identical to that found in an E. coli isolate (GenBank accession no. DQ438952). This gene differs from blaCMY-2 by 1 amino acid. Three of the blaCMY-positive isolates, including the strain positive for blaCMY-23, also contained blaTEM-1b. The Mbandaka isolate was positive for blaSHV-30 with pI 7.0 (33) and also produced an enzyme with a pI 7.6, the nature of which is still under study. Two isolates (1 Senftenberg and 1 Typhimurium) contained blaSHV-12, and both also contained blaOXA and blaTEM-1 genes. Of the 11 Senftenberg isolates, 10 contained blaOXA-1 (n = 9) or blaOXA-9 (n = 1). No isolates contained blaCTX-M genes.
Fluoroquinolone and extended-spectrum cephalosporin coresistance is rare; however, the appearance of this phenotype in 2 commonly isolated serotypes from humans (Typhimurium and Newport) is concerning. Sporadic infections are alarming, but if clonal expansion of an isolate with this phenotype were to take place, as occurred with Salmonella ser. Typhimurium DT104 and Newport-MDRAmpC, the clinical consequences could be dramatic. Statistically significant increases in resistance to nalidixic acid (odds ratio [OR] 6.7, 95% confidence interval [CI] CI 2.6–17.7) and ceftiofur (OR 43.2, 95% CI 10.5–177.4) have been documented among non-Typhi Salmonella of human origin submitted to NARMS during 1996–2003 (4). Of 202 nalidixic acid–resistant non-Typhi Salmonella collected by NARMS during 1996–2003, most were ser. Enteritidis (31%) or Typhimurium (10%). Most of the 324 ceftiofur-resistant non-Typhi Salmonella collected by NARMS during the same time period were ser. Newport (56%) or Typhimurium (23%). A slightly broader geographic representation can be found in the SENTRY surveillance project, which analyzed 786 Salmonella isolates (blood and stool) from medical facilities in Latin America and North America (including Canada) during 2001–2003 (8). Of these, 11% were resistant to nalidixic acid, and 2% exhibited decreased susceptibility to ceftazidime, ceftriaxone, or aztreonam.
Extended-spectrum cephalosporin-resistant Newport and Typhimurium isolates are typically obtained from community-acquired infections. Newport-MDRAmpC infections have been associated with consumption of contaminated beef and unpasteurized dairy products (34). Salmonella containing blaCMY genes have been isolated from ground chicken (Typhimurium DT208), turkey (Agona), and beef (Agona) purchased from retail outlets in the Washington DC area (35). In addition, cattle, chickens, turkeys, pigs, horses, and dogs have all been sources of blaCMY-containing Salmonella, including common serotypes such as Typhimurium, Newport, and Heidelberg (26,36,37). Decreased susceptibility to fluoroquinolones among Salmonella serotypes that typically carry blaCMY genes warrants exploration of factors that could select for decreased susceptibility to fluoroquinolones in animal reservoirs and in the human host.
PFGE showed diversity within some serotypes and indistinguishable strains within others. PFGE diversity among 2 serotypes commonly associated with extended-spectrum cephalosporin resistance (Newport and Typhimurium) is not surprising, given that CMY-producing strains have been seen at least since the late 1990s. Isolates of ser. Enteritidis are highly clonal; therefore, PFGE-indistinguishable patterns among isolates with no apparent epidemiologic link are not unusual. All PFGE-indistinguishable Senftenberg isolates from group 1 were isolated in the same state. Results for the Florida Senftenberg isolates are described elsewhere (16,18).
Salmonella ser. Senftenberg exhibiting decreased susceptibility to fluoroquinolones has been associated with nosocomial infections in healthcare facilities in the United States (18). All 11 isolates contained identical gyrA mutations (S83Y and D87G) and parC mutations (T57S and S80I). These parC mutations have been identified in several Salmonella serotypes including Senftenberg (38). Ten Senftenberg isolates included in this study contained blaOXA genes; the blaOXA-negative Senftenberg strain contained a blaCMY-23 mechanism of extended-spectrum cephalosporin resistance. Acquisition of a blaCMY gene by a traditionally nalidixic acid–resistant serotype warrants further epidemiologic and laboratory investigation. The blaOXA-1 gene has been identified in Salmonella ser. Typhimurium and is reported to be carried by an integron (39); blaOXA-9 has been associated with Tn1331 (40).
The epidemiology of Salmonella with decreased susceptibility to fluoroquinolones is relatively well characterized, as is that of Salmonella with blaCMY-mediated extended-spectrum cephalosporin resistance. Conversely, little is known about the events leading to quinolone and extended-spectrum cephalosporin coresistance and the epidemiology of these infections in humans. Patients with Salmonella infections who exhibit decreased susceptibility to both antimicrobial drug classes should be interviewed to determine risk factors and the effects of antimicrobial drugs and other potential selective factors on this phenomenon.
Dr Whichard is a researcher with NARMS at CDC. Her interests include β-lactamases, multidrug-resistant Salmonella isolates, bacteriophages, and other mobile genetic elements.
We thank Ewelina Lyszkowicz, Linda Gheesling, and Matt Mikoleit for confirming Salmonella serotypes; Anne Whitney and Mike Frace for DNA sequencing; and NARMS-participating laboratories for providing the isolates used in this study.
This work was funded by an Interagency Agreement between the Food and Drug Administration and CDC. G.A.J. was supported in part by grant AI43312 from the National Institutes of Health, US Public Health Service.
- Hohmann EL. Nontyphoidal salmonellosis. Clin Infect Dis. 2001;32:263–9.
- Centers for Disease Control and Prevention. NARMS human isolates final report, 2002. 2005 [cited 2006 Nov 10]. Available from http://www.cdc.gov/narms/annual/2002/2002annualreportfinal.pdf
- Stevenson JE, Gay K, Barrett TJ, Medalla F, Chiller TM, Angulo FJ. Increase in nalidixic acid resistance among non-Typhi Salmonella enterica isolates in the United States from 1996–2003. Antimicrob Agents Chemother. 2007;51:195–7.
- Centers for Disease Control and Prevention. NARMS human isolates final report, 2003. 2006 [cited 2006 Nov 11]. Available from http://www.cdc.gov/narms/annual/2003/NARMS2003AnnualReport.pdf
- Hakanen AJ, Lindgren M, Huovinen P, Jalava J, Siitonen A, Kotilainen P. New quinolone resistance phenomenon in Salmonella enterica: nalidixic acid-susceptible isolates with reduced fluoroquinolone susceptibility. J Clin Microbiol. 2005;43:5775–8.
- Dunne EF, Fey PD, Kludt P, Reporter R, Mostashari F, Shillam P, Emergence of domestically acquired ceftriaxone-resistant Salmonella infections associated with AmpC β-lactamase. JAMA. 2000;284:3151–6.
- Carattoli A, Tosini F, Giles WP, Rupp ME, Hinrichs SH, Angulo FJ, Characterization of plasmids carrying CMY-2 from expanded-spectrum cephalosporin-resistant Salmonella strains isolated in the United States between 1996 and 1998. Antimicrob Agents Chemother. 2002;46:1269–72.
- Biedenbach DJ, Toleman M, Walsh TR, Jones RN. Analysis of Salmonella spp. with resistance to extended-spectrum cephalosporins and fluoroquinolones isolated in North America and Latin America: report from the SENTRY Antimicrobial Surveillance Program (1997–2004). Diagn Microbiol Infect Dis. 2006;54:13–21.
- Boonmar S, Bangtrakulnonth A, Pornruangwong S, Samosornsuk S, Kaneko K, Ogawa M. Significant increase in antibiotic resistance of Salmonella isolates from human beings and chicken meat in Thailand. Vet Microbiol. 1998;62:73–80.
- Threlfall EJ, Skinner JA, Graham A, Ward LR, Smith HR. Resistance to ceftriaxone and cefotaxime in non-typhoidal Salmonella enterica in England and Wales, 1998–99. J Antimicrob Chemother. 2000;46:860–2.
- Bertrand S, Weill FX, Cloeckaert A, Vrints M, Mairiaux E, Praud K, Clonal emergence of extended-spectrum beta-lactamase (CTX-M-2)–producing Salmonella enterica serovar Virchow isolates with reduced susceptibilities to ciprofloxacin among poultry and humans in Belgium and France (2000 to 2003). J Clin Microbiol. 2006;44:2897–903.
- Prabha Adhikari MR, Baliga S. Ciprofloxacin-resistant typhoid with incomplete response to cefotaxime. J Assoc Physicians India. 2002;50:428–9.
- Gay K, Robicsek A, Strahilevitz J, Park CH, Jacoby G, Barrett TJ, Plasmid-mediated quinolone resistance in non-Typhi serotypes of Salmonella enterica. Clin Infect Dis. 2006;43:297–304.
- Yan JJ, Chiou CS, Lauderdale TL, Tsai SH, Wu JJ. Cephalosporin and ciprofloxacin resistance in Salmonella, Taiwan. Emerg Infect Dis. 2005;11:947–50.
- Zhao S, Fedorka-Cray PJ, Friedman S, McDermott PF, Walker RD, Qaiyumi S, Characterization of Salmonella Typhimurium of animal origin obtained from the National Antimicrobial Resistance Monitoring System. Foodborne Pathog Dis. 2005;2:169–81.
- Stamey K, Rossiter S, Kubota K, VanDuyne S, Blackmore C, Farah R, PFGE patterns of multidrug-resistant Salmonella serotype Senftenberg isolated from patients in a Florida hospital nosocomial transmission. Proceedings of the 101st General Meeting Abstracts; 2001 May 20–24; Orlando (FL). Washington: American Society for Microbiology; 2001.
- Zuppardo A, Fiorella PD, Baker R, Farah R, Sieffert D, Hale Y. Genetic profiles of multidrug resistant strains of Salmonella Senftenberg from a nosocomial Florida outbreak. Proceedings of the 102nd General Meeting Abstracts; 2002 May 19–23; Salt Lake City (UT). Washington; American Society for Microbiology; 2002.
- Kay RS, Vandevelde AG, Fiorella PD, Crouse R, Blackmore C, Sanderson R, Outbreak of healthcare-associated infection and colonization with multidrug-resistant Salmonella enterica serovar Senftenberg in Florida. Infect Control Hosp Epidemiol. 2007;28:805–11.
- Popoff MY. Antigenic formulas of the Salmonella serovars. 8th ed. Paris: World Health Organization Collaborating Centre for Reference and Research on Salmonella, Institute Pasteur; 2001.
- Clinical Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; Sixteenth Informational Supplement (M100-S16). Wayne (PA): The Institute; 2006.
- Rasheed JK, Anderson GJ, Yigit H, Queenan AM, Domenech-Sanchez A, Swenson JM, Characterization of the extended-spectrum beta-lactamase reference strain, Klebsiella pneumoniae K6 (ATCC 700603), which produces the novel enzyme SHV-18. Antimicrob Agents Chemother. 2000;44:2382–8.
- Jacoby GA, Chow N, Waites KB. Prevalence of plasmid-mediated quinolone resistance. Antimicrob Agents Chemother. 2003;47:559–62.
- Jacoby GA, Walsh KE, Mills DM, Walker VJ, Oh H, Robicsek A, qnrB, another plasmid-mediated gene for quinolone resistance. Antimicrob Agents Chemother. 2006;50:1178–82.
- Park CH, Robicsek A, Jacoby GA, Sahm D, Hooper DC. Prevalence in the United States of aac(6')-Ib-cr encoding a ciprofloxacin-modifying enzyme. Antimicrob Agents Chemother. 2006;50:3953–5.
- Winokur PL, Vonstein DL, Hoffman LJ, Uhlenhopp EK, Doern GV. Evidence for transfer of CMY-2 AmpC beta-lactamase plasmids between Escherichia coli and Salmonella isolates from food animals and humans. Antimicrob Agents Chemother. 2001;45:2716–22.
- Chen S, Zhao S, White DG, Schroeder CM, Lu R, Yang H, Characterization of multiple-antimicrobial-resistant Salmonella serovars isolated from retail meats. Appl Environ Microbiol. 2004;70:1–7.
- Brinas L, Zarazaga M, Saenz Y, Ruiz-Larrea F, Torres C. Beta-lactamases in ampicillin-resistant Escherichia coli isolates from foods, humans, and healthy animals. Antimicrob Agents Chemother. 2002;46:3156–63.
- Rasheed JK, Jay C, Metchock B, Berkowitz F, Weigel L, Crellin J, Evolution of extended-spectrum beta-lactam resistance (SHV-8) in a strain of Escherichia coli during multiple episodes of bacteremia. Antimicrob Agents Chemother. 1997;41:647–53.
- Yagi T, Kurokawa H, Shibata N, Shibayama K, Arakawa Y. A preliminary survey of extended-spectrum beta-lactamases (ESBLs) in clinical isolates of Klebsiella pneumoniae and Escherichia coli in Japan. FEMS Microbiol Lett. 2000;184:53–6.
- Woodford N, Fagan EJ, Ellington MJ. Multiplex PCR for rapid detection of genes encoding CTX-M extended-spectrum β-lactamases. J Antimicrob Chemother. 2006;57:154–5.
- Eaves DJ, Randall L, Gray DT, Buckley A, Woodward MJ, White AP, Prevalence of mutations within the quinolone resistance-determining region of gyrA, gyrB, parC, and parE and association with antibiotic resistance in quinolone-resistant Salmonella enterica. Antimicrob Agents Chemother. 2004;48:4012–5.
- Ribot EM, Fair MA, Gautom R, Cameron DN, Hunter SB, Swaminathan B, Standardization of pulsed-field gel electrophoresis protocols for the subtyping of Escherichia coli O157:H7, Salmonella, and Shigella for PulseNet. Foodborne Pathog Dis. 2006;3:59–67.
- Szabo D, Melan MA, Hujer AM, Bonomo RA, Hujer KM, Bethel CR, Molecular analysis of the simultaneous production of two SHV-type extended-spectrum beta-lactamases in a clinical isolate of Enterobacter cloacae by using single-nucleotide polymorphism genotyping. Antimicrob Agents Chemother. 2005;49:4716–20.
- Varma JK, Marcus R, Stenzel SA, Hanna SS, Gettner S, Anderson BJ, Highly resistant Salmonella Newport-MDRAmpC transmitted through the domestic US food supply: a FoodNet case-control study of sporadic Salmonella Newport infections, 2002–2003. J Infect Dis. 2006;194:222–30.
- White DG, Zhao S, Sudler R, Ayers S, Friedman S, Chen S, The isolation of antibiotic-resistant Salmonella from retail ground meats. N Engl J Med. 2001;345:1147–54.
- Rankin SC, Aceto H, Cassidy J, Holt J, Young S, Love B, Molecular characterization of cephalosporin-resistant Salmonella enterica serotype Newport isolates from animals in Pennsylvania. J Clin Microbiol. 2002;40:4679–84.
- Winokur PL, Brueggemann A, DeSalvo DL, Hoffmann L, Apley MD, Uhlenhopp EK, Animal and human multidrug-resistant, cephalosporin-resistant Salmonella isolates expressing a plasmid-mediated CMY-2 AmpC beta-lactamase. Antimicrob Agents Chemother. 2000;44:2777–83.
- Hopkins KL, Arnold C, Threlfall EJ. Rapid detection of gyrA and parC mutations in quinolone-resistant Salmonella enterica using pyrosequencing technology. J Microbiol Methods. 2007;68:163–71.
- Yamamoto T, Tanaka M, Nohara C, Fukunaga Y, Yamagishi S. Transposition of the oxacillin-hydrolyzing penicillinase gene. J Bacteriol. 1981;145:808–13.
- Tolmasky ME, Crosa JH. Genetic organization of antibiotic resistance genes (aac(6')-Ib, aadA, and oxa9) in the multiresistance transposon Tn1331. Plasmid. 1993;29:31–40.