Ciprofloxacin-resistant Salmonella enterica Serotype Typhi, United States, 1999-2008.
ABSTRACT We report 9 ciprofloxacin-resistant Salmonella enterica serotype Typhi isolates submitted to the US National Antimicrobial Resistance Monitoring System during 1999-2008. The first 2 had indistinguishable pulsed-field gel electrophoresis patterns and identical gyrA and parC mutations. Eight of the 9 patients had traveled to India within 30 days before illness onset.
Article: Typhoid fever in the United States, 1985-1994: changing risks of international travel and increasing antimicrobial resistance.[show abstract] [hide abstract]
ABSTRACT: Typhoid fever is a potentially fatal illness common in the less industrialized world. In the United States, the majority of cases occur in travelers to other countries. We reviewed surveillance forms submitted to the Centers for Disease Control and Prevention, Atlanta, Ga, for patients with culture-confirmed typhoid fever between 1985 and 1994. The Centers for Disease Control and Prevention received report forms for 2445 cases of typhoid fever. Median age of patients was 24 years (range, 0-89 years). Ten (0.4%) died. Seventy-two percent reported international travel within the 30 days before onset of illness. Six countries accounted for 80% of cases: Mexico (28%), India (25%), the Philippines (10%), Pakistan (8%), El Salvador (5%), and Haiti (4%). The percentage of cases associated with visiting Mexico decreased from 46% in 1985 to 23% in 1994, while the percentage of cases associated with visiting the Indian subcontinent increased from 25% in 1985 to 37% in 1994. The incidence of typhoid fever in US citizens traveling to the Indian subcontinent was at least 18 times higher than for any other geographic region. Complete data on antimicrobial susceptibility to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole were reported for 330 (13%) Salmonella Typhi isolates. Isolates from 1990 to 1994 were more likely than isolates from 1985 to 1989 to be resistant to any of these antimicrobial agents (30% vs 12%; P<.001) and to be resistant to all 3 agents (12% vs 0.6%; P<.001). American travelers to less industrialized countries, especially those traveling to the Indian subcontinent, continue to be at risk for typhoid fever. Antimicrobial resistance has increased, and a quinolone or third-generation cephalosporin may be the best choice for empirical treatment of typhoid fever.Archives of Internal Medicine 03/1998; 158(6):633-8. · 11.46 Impact Factor
Article: Laboratory-based surveillance of Salmonella serotype Typhi infections in the United States: antimicrobial resistance on the rise.[show abstract] [hide abstract]
ABSTRACT: Multidrug-resistant Salmonella serotype Typhi infections have been reported worldwide, but data on the incidence of resistant strains in the United States are lacking. To determine the incidence of antimicrobial-resistant Salmonella Typhi infections and to identify risk factors for infection. Cross-sectional laboratory-based surveillance study. A total of 293 persons with symptomatic typhoid fever who had Salmonella Typhi isolates and epidemiological information submitted to US public health departments and laboratories from June 1, 1996, to May 31, 1997. Proportion of Salmonella Typhi isolates demonstrating resistance to 12 antimicrobial agents; patient epidemiological factors associated with drug-resistant infections. Median age was 21 years (range, 3 months to 84 years); 56% were male. Two hundred twenty-eight (80%) were hospitalized; 2 died. In the 6 weeks before illness onset, 81% of patients had traveled abroad. Seventy-four Salmonella Typhi isolates (25%) were resistant to 1 or more antimicrobial agent, and 51 (17%) were resistant to 5 or more agents, including ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole (multidrug-resistant Salmonella Typhi [MDRST]). Although no resistance to ciprofloxacin or ceftriaxone was observed, 20 isolates (7%) were nalidixic acid-resistant (NARST). Patients with MDRST and NARST infections were more likely to report travel outside the United States, particularly to the Indian subcontinent (Bangladesh, India, and Pakistan) (odds ratio [OR], 29.3; 95% confidence interval [CI], 6.8-126.7; P<.001 and OR, 35.9; 95% CI, 3.4-377.3; P<.001, respectively). Our data suggest that ciprofloxacin and ceftriaxone are appropriate empirical therapy for suspected typhoid fever; however, resistance may be anticipated. Continued monitoring of antimicrobial resistance among Salmonella Typhi strains will help determine vaccination and treatment policies. JAMA. 2000;283:2668-2673.JAMA The Journal of the American Medical Association 283(20):2668-73. · 30.03 Impact Factor
Article: Molecular characterization of ciprofloxacin-resistant Salmonella enterica serovar Typhi and Paratyphi A causing enteric fever in India.[show abstract] [hide abstract]
ABSTRACT: To define the genetic characteristics and resistance mechanisms of clinical isolates of Salmonella enterica serovar Typhi (S. Typhi) and S. enterica serovar Paratyphi A (S. Paratyphi A) exhibiting high-level fluoroquinolones resistance. Three S. Typhi and two S. Paratyphi A ciprofloxacin-resistant isolates (MICs > 4 mg/L) were compared with isolates with reduced susceptibility to ciprofloxacin (MICs 0.125-1 mg/L) by PFGE, plasmid analysis, presence of integrons and nucleotide changes in topoisomerase genes. In S. Typhi and Paratyphi A, a single gyrA mutation (Ser-83-->Phe or Ser-83-->Tyr) was associated with reduced susceptibility to ciprofloxacin (MICs 0.125-1 mg/L); an additional mutation in parC (Ser-80-->Ile, Ser-80-->Arg, Asp-69-->Glu or Gly-78-->Asp) was accompanied by an increase in ciprofloxacin MIC (> or = 0.5 mg/L). Three mutations conferred ciprofloxacin resistance: two in gyrA (Ser-83-->Phe and Asp-87-->Asn or Asp-87-->Gly) and one in parC. This is the first report of parC mutations in S. Typhi. Ciprofloxacin-resistant S. Typhi and S. Paratyphi A differed in their MICs and mutations in gyrA and parC. Moreover S. Typhi harboured a 50 kb transferable plasmid carrying a class 1 integron (dfrA15/aadA1) that confers resistance to co-trimoxazole and tetracycline but not to ciprofloxacin. PFGE revealed undistinguishable XbaI fragment patterns in ciprofloxacin-resistant S. Typhi as well as in S. Paratyphi A isolates and showed that ciprofloxacin-resistant S. Typhi have emerged from a clonally related isolate with reduced susceptibility to ciprofloxacin after sequential acquisition of a second mutation in gyrA. To our knowledge this is the first report of molecular characterization of S. Typhi with full resistance to ciprofloxacin. Notably, the presence of a plasmid-borne integron in ciprofloxacin-resistant S. Typhi may lead to a situation of untreatable enteric fever.Journal of Antimicrobial Chemotherapy 12/2006; 58(6):1139-44. · 5.07 Impact Factor
Ciprofl oxac in-
S erotype Typhi,
United S tates,
Felicita Medalla, Maria Sjölund-Karlsson,
Sanghyuk Shin, Emily Harvey, Kevin Joyce,
Lisa Theobald, Benjamin L. Nygren,
Gary Pecic, Kathryn Gay, Jana Austin,
Andrew Stuart, Elizabeth Blanton, Eric D. Mintz,
Jean M. Whichard, and Ezra J. Barzilay
We report 9 ciprofl oxacin-resistant Salmonella enterica
serotype Typhi isolates submitted to the US National
Antimicrobial Resistance Monitoring System during
1999–2008. The fi rst 2 had indistinguishable pulsed-fi eld
gel electrophoresis patterns and identical gyrA and parC
mutations. Eight of the 9 patients had traveled to India
within 30 days before illness onset.
rare in the United States in the era of modern sanitation
(1,2). However, typhoid fever remains common in many
developing countries. In the United States, 72%–81% of
patients with typhoid fever report international travel in the
month before illness onset (1,3–5). Highest risk has been
associated with travel to southern Asia (1–5).
Fluoroquinolones (e.g., ciprofl oxacin) are frequently
used to treat typhoid fever in adults (4,6). Ciprofl oxacin
resistance is rare; however, resistance to the quinolone
nalidixic acid in the US National Antimicrobial Resistance
Monitoring System (NARMS) increased from 19% of
isolates tested in 1999 to 59% in 2008 (7). Nalidixic
acid resistance in S. enterica serotype Typhi, which
has been associated with overseas travel, particularly to
southern Asia, correlates with decreased susceptibility to
yphoid fever, caused by Salmonella enterica serotype
Typhi, is a systemic bacterial illness that has been
ciprofl oxacin (MIC >0.12 μg/mL) (4–6,8). Increased risk
for fl uoroquinolone treatment failure has been demonstrated
in Salmonella infections from strains with decreased
susceptibility to ciprofl oxacin (6,8,9). Chromosomal point
mutations in the gyrA and parC topoisomerase genes
are mechanisms of quinolone resistance in Salmonella
spp. Other resistance mechanisms include effl ux pumps,
reduced outer membrane permeability, and plasmid-borne
genes (e.g., qnr, aac-6′-Ib-cr genes) (6,8,10–12). We report
9 ciprofl oxacin-resistant (MIC >4 μg/mL) S. enterica
serotype Typhi isolates detected in the United States during
State public health laboratories receive Salmonella
isolates from clinical diagnostic laboratories as part of routine
surveillance. State and local health department offi cials
report demographic, clinical, and travel information about
laboratory-confi rmed typhoid fever on a standard form
to the Centers for Disease Control and Prevention (CDC,
Atlanta, GA, USA). Participating states began submitting
all S. enterica serotype Typhi isolates to NARMS in
1999; since 2003, all state public health laboratories have
participated. Isolates were tested for susceptibility by using
broth microdilution (Sensititre: Trek Diagnostics, Westlake,
OH, USA). MICs were determined for 15 antimicrobial
agents and interpreted by using Clinical and Laboratory
Standards Institute (CLSI) criteria when available (Table
1) (7,13). For ciprofl oxacin-resistant isolates, subtyping by
pulsed-fi eld gel electrophoresis (PFGE) was performed by
using the protocol established by the National Molecular
Subtyping Network for Foodborne Disease Surveillance
(PulseNet) (14). PFGE pattern similarity was assessed by
cluster analysis (Dice, UPGMA [unweighted pair group
method using arithmetic averages]) and band-matching
applications of BioNumerics software (Applied Maths,
Sint-Martens-Latem, Belgium) and confi rmed by visual
comparison (Figure). For ciprofl oxacin-resistant isolates
detected for 1999–2005, sequencing of the quinolone
resistance–determining region (QRDR; defi ned as amino
acids 67–106 for gyrA) was performed according to the
methods described by Crump et al. (6), and additional
patient information (e.g., antimicrobial drug treatment) was
requested by using a questionnaire with institutional review
During 1999–2005, we detected 2 (0.1%) cases of
ciprofl oxacin resistance among 1,690 S. enterica serotype
Typhi isolates. Case reports follow.
In 2003, a 1-year-old girl had onset of fever 1 day
before arriving in the United States from India. A blood
specimen collected 3 days after fever onset yielded S.
enterica serotype Typhi. Diarrhea or vomiting at time of
specimen collection was not reported. Information about
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 17, No. 6, June 2011 1095
Author affi liations: Centers for Disease Control and Prevention,
Atlanta, Georgia, USA (F. Medalla, M. Sjölund-Karlsson, K. Joyce,
L. Theobald, B.L. Nygren, G. Pecic, K. Gay, J. Austin, A. Stuart,
E. Blanton, E.D. Mintz, J.M. Whichard, E.J. Barzilay); California
Emerging Infections Program, Oakland, California, USA (S. Shin);
and Massachusetts Department of Public Health, Jamaica Plain,
Massachusetts, USA (E. Harvey)
antimicrobial drug treatment was not available. The child
was hospitalized for 14 days.
In 2005, a 2-year-old girl had onset of diarrhea,
which was treated with ofl oxacin, 2 days before she
arrived in the United States from India. Seven days later,
she continued to have diarrhea, and fever, vomiting, and
abdominal cramps developed. She was hospitalized and
treated with antimicrobial agents, including ciprofl oxacin.
Blood and fecal specimens collected 3 weeks after illness
onset yielded S. enterica serotype Typhi. The patient was
discharged after 14 days of hospitalization. She had lived
in India for 6 months before traveling to the United States.
The S. enterica serotype Typhi isolates were resistant
to ciprofl oxacin (Tables 1, 2) and had indistinguishable
PFGE patterns when restriction enzymes XbaI and
BlnI were used: PulseNet-designated XbaI pattern
JPPX01.0026 and BlnI pattern JPPA26.0110 (Table
2; Figure). QRDR sequencing showed gyrA mutations
resulting in a serine to tyrosine substitution at codon 83
and an aspartic acid to asparagine substitution at codon
87, and a parC mutation conferring a serine to isoleucine
substitution at codon 80.
Seven (0.6%) ciprofl oxacin-resistant infections were
detected among patients from whom 1,131 S. enterica
serotype Typhi isolates were submitted during 2006–2008
(Table 2). The 7 cases occurred in 2006 and 2007. Patients
were a median of 22 years of age (range 5–48 years); 5
(71%) were male. All 6 patients with known travel histories
reported travel to India in the 30 days before illness onset.
In addition to XbaI JPPX01.0026 and BlnI JPPA26.0110, 3
different XbaI and BlnI pattern combinations were detected
in the 7 isolates (Table 2; Figure).
We describe ciprofl oxacin-resistant S. enterica
serotype Typhi isolates from 9 patients in the United
States. The fi rst 5 cases were reported previously in
aggregated form, without molecular characterization
of the isolates (5). The fi rst 2 patients were young
children apparently infected in India in 2003 and 2005.
1096 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 17, No. 6, June 2011
Table 1. MICs of antimicrobial agents tested for 9 ciprofloxacin-resistant Salmonella enterica serotype Typhi isolates detected in the
National Antimicrobial Resistance Monitoring System, United States, 1999–2008
MIC, μg/mL,* by patient no. (isolate)
(MA-03) (CA-05) (CA-06)
Ciprofloxacin >4>4 >4
Nalidixic acid >32>32>32
Amoxicillin-clavulanic acid <1/0.5 <1/0.5<1/0.5
Ceftiofur 0.50.5 0.5
Folate pathway inhibitors
Sulfonamide‡ >512 >256 <16
Ampicillin 2<1 <1
Tetracycline >32 >32<4
*Classes of antimicrobial agents defined by the Clinical and Laboratory Standards Institute (CLSI) were used to categorize agents (7,13). MICs were
interpreted by using CLSI criteria when available (7,13): ciprofloxacin (resistance breakpoint, >4 μg/mL); nalidixic acid (>32); amikacin (>64); gentamicin
(>16); kanamycin (>64); amoxicillin-clavulanic acid (>32/16); cefoxitin (>32); ceftiofur (>8); ceftriaxone (>4); sulfamethoxazole/sulfisoxazole (>512);
trimethoprim-sulfamethoxazole (>4/76); ampicillin (>32); chloramphenicol (>32); and tetracycline (>16). For streptomycin, resistance was defined as MIC
>64 μg/mL (7). If growth was not inhibited by the highest concentration of the agent in the panel, the MIC was reported as above the highest
†Isolate was cultured from a blood specimen. Another isolate was cultured from fecal samples, which had MIC <0.5 μg/mL for amikacin and same MICs
for other agents tested.
‡Sulfamethoxazole was used during 1999–2003 and sulfisoxazole since 2004 to represent sulfonamides.
Antimicrobial class and agent*
Patient 2† Patient 3 Patient 4
8/4<1/0.5 <1/0.5<1/0.5 <1/0.5<1/0.5
>32<1 <1 <1<1
<4>32 <4 >32<4 <4
Ciprofl oxacin-Resistant S. enterica ser. Typhi
Six additional patients, who were detected in 2006 and
2007, also reported travel to India. Travel to the Indian
subcontinent has been associated with nalidixic acid–
resistant S. enterica serotype Typhi infection; however,
ciprofl oxacin-resistant infections are rarely reported by
using current CLSI criteria (4,5,11). Other resistance
patterns were fi rst described in southern Asia, where the
incidence of typhoid fever is high and antimicrobial agents
are widely available without prescription, providing the
opportunity for the development and selection of resistant
Other than reports by 8 patients of travel to India,
we have no information about possible shared exposures,
such as specifi c locations visited, sources of food or water,
or contact with carriers of S. enterica serotype Typhi.
However, the indistinguishable PFGE XbaI and BlnI
patterns and identical gyrA and parC mutations of isolates
from the fi rst 2 patients suggest that, although typhoid
fever occurred nearly 2 years apart, the same ciprofl oxacin-
resistant strain is likely to have been involved. After 2005,
different XbaI and BlnI patterns have been identifi ed in
ciprofl oxacin-resistant isolates, indicating independent
selection of ciprofl oxacin resistance in different strains.
The gyrA and parC mutations of isolates from the fi rst 2
patients were reported in ciprofl oxacin-resistant S. enterica
serotype Typhi in India (11). The 2 gyrA mutations are well
characterized and known to be associated with quinolone
resistance; 2 point mutations in gyrA and 1 in parC confer
fl uoroquinolone resistance (8,10–12). Further studies,
including characterization of other resistance mechanisms,
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 17, No. 6, June 2011 1097
Figure. Pulsed-fi eld gel electrophoresis (PFGE) XbaI (A) and BlnI (B) patterns of 9 ciprofl oxacin-resistant Salmonella enterica serotype
Typhi isolates detected in the National Antimicrobial Resistance Monitoring System, 1999–2008. PFGE pattern similarity was assessed by
cluster analysis (Dice, UPGMA [unweighted pair group method using arithmetic average]) and band-matching applications of BioNumerics
software (Applied Maths, Sint-Martens-Latem, Belgium) and confi rmed by visual comparison. PulseNet only considers band markings
found within the scale of the global standard, which are all bands between 20.5 kb and 1,135 kb. The cluster parameters are Dice
coeffi cient and UPGMA with the tolerance of band position of 1.5% and optimization of 1.5%.
Table 2. Patient and isolate description, resistance to other antimicrobial agents, PFGE pattern, and travel reported for 9 ciprofloxacin-
resistant Salmonella enterica serotype Typhi infections detected in the National Antimicrobial Resistance Monitoring System, United
(isolate) sex Sitecollection year source
1 (MA-03) 1/FMA2003 Blood Cot, Fis, Nal, Tet
2 (CA-05) 2/F CA2005 BloodCot, Fis, Nal, Tet
3 (CA-06) 26/F CA2006 Blood
4 (TX-06) 8/M TX2006 BloodAmp, Chl, Cot,
Age, y/ SpecimenSpecimen Resistance to
Fis, Nal, Str
Cot, Fis, Nal, Tet
Cot, Fis, Nal, Tet
*PFGE, pulsed-field gel electrophoresis. State/local public health laboratories that submitted isolates: MA, Massachusetts; CA, California; TX, Texas; AZ,
Arizona; NYC, New York City; NJ, New Jersey; LAC, Los Angeles County, California. Resistance to antimicrobial agents other than ciprofloxacin: Cot,
trimethoprim–sulfamethoxazole; Fis, sulfamethoxazole or sulfisoxazole; Nal, nalidixic acid; Tet, tetracycline; Amp, ampicillin; Chl, chloramphenicol; Str,
†National Molecular Subtyping Network for Foodborne Disease Surveillance (PulseNet)–designated PFGE patterns using restriction enzyme XbaI (data
as of 2009 Oct 21): JPPX01.0026, the most common XbaI pattern among 3,233 isolates with reported XbaI pattern in PulseNet, was detected in 486
(15.0%); JPPX01.0465 and JPPX01.0506 each were detected in 12 (0.4%) isolates.
‡PulseNet-designated PFGE patterns using restriction enzyme BlnI (data as of 2009 Oct 21): JPPA26.0002, the most common BlnI pattern among 409
isolates with reported BlnI pattern in PulseNet, was detected in 61 (14.9%) isolates; JPPA26.0110 was detected in 5 (1.2%), JPPA26.0187 was detected
in 3 (0.7%), and JPPA26.0170 was detected in 1 (0.2%).
§Travel outside the United States reported in the 30 d before illness onset; patient 4 also traveled to Bangladesh and the United Arab Emirates.
are needed to track the evolution of fl uoroquinolone-
resistant S. enterica serotype Typhi.
Although the ciprofl oxacin resistance we detected
using current CLSI criteria is rare in S. enterica serotype
Typhi, nalidixic acid resistance, which correlates with
decreased susceptibility to ciprofl oxacin, has increased (7).
Clinicians should be aware that infection with Salmonella
spp. with decreased susceptibility to ciprofl oxacin may
not respond satisfactorily to this agent (6,8,9,13,15). In
addition, identifi cation of ciprofl oxacin-resistant cases has
been increasing. In the presence of quinolone resistance,
third-generation cephalosporins, such as ceftriaxone,
can be used (2,6,8,15). Recent clinical trials suggest that
azithromycin might be useful for treating uncomplicated
typhoid fever (2,8,9,15). Recommendations for empiric
treatment of typhoid fever in the United States are best
developed by using information about antimicrobial drug
resistance trends in isolates from countries where the
infection was acquired.
We thank the health departments and public health
laboratories in the 50 states; Los Angeles County, California; New
York City, New York; and Houston, Texas, for their participation
in NARMS, the National Typhoid Fever Surveillance System,
and PulseNet. We are grateful to Matthew Mikoleit, Susan Van
Duyne, Nancy Garrett, and Efrain Ribot for their assistance.
The US Food and Drug Administration provides funding
support for NARMS.
Dr Medalla is an epidemiologist with the Division of
Foodborne, Waterborne, and Environmental Diseases, National
Center for Emerging and Zoonotic Infectious Diseases, Centers
for Disease Control and Prevention. Her main research interests
include antimicrobial resistance in foodborne pathogens.
1. Mermin JH, Townes JM, Gerber M, Dolan N, Mintz ED, Tauxe RV.
Typhoid fever in the United States, 1985–1994: changing risks of
international travel and increasing antimicrobial resistance. Arch In-
tern Med. 1998;158:633–8. doi:10.1001/archinte.158.6.633
2. Connor BA, Schwartz E. Typhoid and paratyphoid fever in trav-
elers. Lancet Infect Dis. 2005;5:623–8. doi:10.1016/S1473-
3. Centers for Disease Control and Prevention. Summary of notifi able
diseases—United States, 2006. MMWR. 2008;55:32,77.
4. Ackers ML, Puhr ND, Tauxe RV, Mintz ED. Laboratory-based
surveillance of Salmonella serotype Typhi infections in the United
States: antimicrobial resistance on the rise. JAMA. 2000;283:2668–
5. Lynch MF, Blanton EM, Bulens S, Polyak C, Vojdani J, Stevenson
J, et al. Typhoid fever in the United States, 1999–2006: trends in
quinolone-resistant cases among international travelers. JAMA.
6. Crump JA, Kretsinger K, Gay K, Hoekstra RM, Vugia DJ, Hurd
S, et al. Clinical response and outcome of infection with Salmo-
nella enterica serotype Typhi with decreased susceptibility to fl uo-
roquinolones: a United States FoodNet multicenter retrospective
cohort study. Antimicrob Agents Chemother. 2008;52:1278–84.
7. Centers for Disease Control and Prevention. National Antimicrobial
Resistance Monitoring System for Enteric Bacteria (NARMS): hu-
man isolates fi nal report, 2008. Atlanta: US Department of Health
and Human Services; 2010.
8. Cooke FJ, Wain J. The emergence of antibiotic resistance in ty-
phoid fever. Travel Med Infect Dis. 2004;2:67–74. doi:10.1016/j.
9. Parry CM, Ho VA, Phuong le T, Bay PV, Lanh MN, Tung le T, et
al. Randomized controlled comparison of ofl oxacin, azithromycin,
and an ofl oxacin-azithromycin combination for treatment of multi-
drug-resistant and nalidixic acid-resistant typhoid fever. Antimicrob
Agents Chemother. 2007;51:819–25. doi:10.1128/AAC.00447-06
10. Hopkins KL, Davies RH, Threlfall EJ. Mechanisms of quinolone
resistance in Escherichia coli and Salmonella: recent developments.
Int J Antimicrob Agents. 2005;25:358–73. doi:10.1016/j.ijantimicag.
11. Gaind R, Paglietti B, Murgia M, Dawar R, Uzzau S, Cappuccinelli
P, et al. Molecular characterization of ciprofl oxacin-resistant Salmo-
nella enterica serovar Typhi and Paratyphi A causing enteric fever in
India. J Antimicrob Chemother. 2006;58:1139–44. doi:10.1093/jac/
12. Turner AK, Nair S, Wain J. The acquisition of full fl uoroquinolone
resistance in Salmonella Typhi by accumulation of point mutations
in the topoisomerase targets. J Antimicrob Chemother. 2006;58:733–
13. Clinical and Laboratory Standards Institute. Performance standards
for antimicrobial susceptibility testing: twentieth informational sup-
plement. Wayne (PA): The Institute; 2010.
14. Ribot EM, Fair MA, Gautom R, Cameron DN, Hunter SB, Swami-
nathan B, et al. Standardization of pulsed-fi eld gel electrophoresis
protocols for the subtyping of Escherichia coli O157:H7, Salmonel-
la, and Shigella for PulseNet. Foodborne Pathog Dis. 2006;3:59–67.
15. Crump JA, Mintz ED. Global trends in typhoid and paratyphoid fe-
ver. Clin Infect Dis. 2010;50:241–6. doi:10.1086/649541
Address for correspondence: Felicita Medalla, Centers for Disease
Control and Prevention, 1600 Clifton Rd NE, Mailstop D63, Atlanta, GA
30333, USA; email: firstname.lastname@example.org
1098 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 17, No. 6, June 2011