Clinically Important Resistance among Salmonella enterica Serotype Typhi Isolates—United States, 2003–2015

Abstract Background Salmonella Typhi (Typhi) causes typhoid fever, accounting for an estimated 5,700 illnesses and 623 hospitalizations per year in the United States. Most infections are acquired during travel to regions outside the United States where typhoid fever is prevalent and antimicrobial resistance is a problem. Fluoroquinolones (e.g., ciprofloxacin) are considered the treatment of choice for susceptible Typhi infections due to their superior ability to concentrate intracellularly and in bile, however, nonsusceptibility has been associated with treatment failure or delayed response. Azithromycin and ceftriaxone are treatment options. We describe antimicrobial susceptibility among Typhi isolates in the United States and the implications for management. Methods The National Antimicrobial Resistance Monitoring System at CDC conducts susceptibility testing on all Typhi isolates submitted by public health laboratories. We used broth microdilution to determine minimum inhibitory concentrations (MICs) to agents representing 9 antimicrobial classes and categorized isolates according to criteria from the Clinical and Laboratory Standards Institute. We defined ciprofloxacin nonsusceptibility as MIC ≥0.12 μg/mL, ciprofloxacin resistance as MIC ≥1, azithromycin resistance as MIC ≥32, and ceftriaxone resistance as MIC ≥4. Results From 2003–2015, isolates were tested from 4,550 patients; 2,760 (61%) were ciprofloxacin nonsusceptible, 4% were ciprofloxacin resistant. One isolate was azithromycin resistant and none were ceftriaxone resistant. Ciprofloxacin nonsusceptibility increased from 39% in 2003 to 66% in 2015; resistance increased from 0.3% to 8%. Median age of patients was 23 years (range 1–99 years), 53% were male, most were from the Northeast (33%) or the West (29%), and 74% had an isolate from blood. Conclusion Two thirds of Typhi isolates exhibited ciprofloxacin nonsusceptibility, which has increased over the last decade, and full resistance is increasing. Clinicians should be aware of high rates of fluoroquinolone nonsusceptibility when selecting empiric therapy and should tailor antimicrobial treatment to susceptibility results when feasible. Azithromycin and ceftriaxone remain important treatment options. Disclosures All authors: No reported disclosures.

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Drug-Resistant Salmonella typhi in Pakistan

Clinical Pediatrics ◽

10.1177/0009922819881203 ◽

2019 ◽

Vol 59 (1) ◽

pp. 31-33 ◽

Cited By ~ 1

Author(s):

Christine E. Petrin ◽

Russell W. Steele ◽

Elizabeth A. Margolis ◽

Justin M. Rabon ◽

Holly Martin ◽

...

Keyword(s):

United States ◽

Typhoid Fever ◽

Enteric Fever ◽

The United States ◽

Salmonella Typhi ◽

Antimicrobial Treatment ◽

Third Generation ◽

Drug Resistant ◽

Oral Transmission ◽

Third Generation Cephalosporins

Enteric fever (formerly typhoid fever) is a bacterial illness caused by fecal-oral transmission of Salmonella typhi or paratyphi. In early 2018, an outbreak of Salmonella typhi resistant to third-generation cephalosporins, ampicillin, ciprofloxacin, trimethroprim-sulfamethoxazole, and chloramphenicol was reported in Pakistan. This strain, termed “extensively resistant typhi,” has infected more than 5000 patients in endemic areas of South Asia, as well as travelers to and from these areas, including 5 cases in the United States. We present the case of one such child who developed extensively resistant enteric fever during a recent visit to Pakistan and required broader antimicrobial treatment than typically required. Clinicians should be aware that incoming cases of enteric fever may be nonsusceptible to commonly recommended antibiotics and that extensively resistant typhi requires treatment with carbapenems such as meropenem or azithromycin.

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165. Emergence of Extensively Drug-Resistant Salmonella enterica Serotype Typhi Infections—United States, 2008–2020

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.165 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S99-S100

Author(s):

Felicita Medalla ◽

Louise Francois Watkins ◽

Michael Hughes ◽

Meseret Birhane ◽

Layne Dorough ◽

...

Keyword(s):

United States ◽

Typhoid Fever ◽

The United States ◽

Empiric Therapy ◽

Salmonella Typhi ◽

International Travel ◽

Drug Resistant ◽

Extensively Drug Resistant ◽

Large Outbreak ◽

Control And Prevention

Abstract Background Typhoid fever, caused by Salmonella Typhi, is fatal in 12%–30% of patients not treated with appropriate antibiotics. In 2016, a large outbreak of extensively drug-resistant (XDR) Typhi infections began in Pakistan with cases reported globally, including the United States. In 2021, the Centers for Disease Control and Prevention (CDC) issued a health advisory on XDR infections among U.S. residents without international travel. We describe resistance of Typhi infections diagnosed in the United States to help guide treatment decisions. Methods Typhoid fever is a nationally notifiable disease. Health departments report cases to CDC through the National Typhoid and Paratyphoid Fever Surveillance system. Isolates are submitted to the National Antimicrobial Resistance Monitoring System for antimicrobial susceptibility testing (AST) using broth microdilution. AST results are categorized by Clinical and Laboratory Standards Institute criteria. We defined XDR as resistant to ceftriaxone, ampicillin, chloramphenicol, and co-trimoxazole, and nonsusceptible to ciprofloxacin. Results During 2008–2019, of 4,637 Typhi isolates, 52 (1%) were ceftriaxone resistant (axo-R); 71% were ciprofloxacin nonsusceptible, 1 azithromycin resistant (azm-R), and none meropenem resistant. XDR was first detected in 2018, in 2% of 474 isolates and increased to 7% of 535 in 2019. Of the 52 axo-R isolates, 46 were XDR, of which 45 were from travelers to Pakistan, and one from a non-traveler; 6 were not XDR, of which 4 were linked to travel to Iraq. In preliminary 2020 reports, 23 isolates were XDR; 14 were from travelers to Pakistan, 8 from non-travelers, and 1 from someone with unknown travel status. Among those with XDR infection, median age was 11 years (range 1–62), 54% were female, and 62% were from 6 states. Conclusion Ceftriaxone-resistant Typhi infections, mostly XDR, are increasing. Clinicians should ask patients with suspected Typhi infections about travel and adjust treatment based on susceptibility results. Carbapenem, azithromycin, or both may be considered for empiric therapy of typhoid fever among travelers to Pakistan or Iraq and in uncommon instances when persons report no international travel. Ceftriaxone is an empiric therapy option for travelers to countries other than Pakistan and Iraq. Disclosures All Authors: No reported disclosures

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Population-Based Surveillance of Neisseria meningitidis Antimicrobial Resistance in the United States

Open Forum Infectious Diseases ◽

10.1093/ofid/ofv117 ◽

2015 ◽

Vol 2 (3) ◽

Cited By ~ 29

Author(s):

Brian H. Harcourt ◽

Raydel D. Anderson ◽

Henry M. Wu ◽

Amanda C. Cohn ◽

Jessica R. MacNeil ◽

...

Keyword(s):

United States ◽

Antimicrobial Resistance ◽

Neisseria Meningitidis ◽

Susceptibility Testing ◽

The United States ◽

Population Based ◽

Antimicrobial Treatment ◽

Penicillin G ◽

Gyra Gene ◽

Active Population

Abstract Background. Antimicrobial treatment and chemoprophylaxis of patients and their close contacts is critical to reduce the morbidity and mortality and prevent secondary cases of meningococcal disease. Through the 1990's, the prevalence of antimicrobial resistance to commonly used antimicrobials among Neisseria meningitidis was low in the United States. Susceptibility testing was performed to ascertain whether the proportions of isolates with reduced susceptibility to antimicrobials commonly used for N meningitidis have increased since 2004 in the United States. Methods. Antimicrobial susceptibility testing was performed by broth microdilution on 466 isolates of N meningitidis collected in 2004, 2008, 2010, and 2011 from an active, population-based surveillance system for susceptibility to ceftriaxone, ciprofloxacin, penicillin G, rifampin, and azithromycin. The molecular mechanism of reduced susceptibility was investigated for isolates with intermediate or resistant phenotypes. Results. All isolates were susceptible to ceftriaxone and azithromycin, 10.3% were penicillin G intermediate (range, 8% in 2008–16.7% in 2010), and <1% were ciprofloxacin, rifampin, or penicillin G resistant. Of the penicillin G intermediate or resistant isolates, 63% contained mutations in the penA gene associated with reduced susceptibility to penicillin G. All ciprofloxacin-resistant isolates contained mutations in the gyrA gene associated with reduced susceptibility. Conclusions. Resistance of N meningitidis to antimicrobials used for empirical treatment of meningitis in the United States has not been detected, and resistance to penicillin G and chemoprophylaxis agents remains uncommon. Therapeutic agent recommendations remain valid. Although periodic surveillance is warranted to monitor trends in susceptibility, routine clinical testing may be of little use.

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Typhoid fever imported from Mexico to Switzerland. Studies on R factor mediated chloramphenicol resistance

Journal of Hygiene ◽

10.1017/s0022172400046490 ◽

1973 ◽

Vol 71 (3) ◽

pp. 509-513 ◽

Cited By ~ 5

Author(s):

F. A. Waldvogel ◽

J. S. Pitton

Keyword(s):

United States ◽

Typhoid Fever ◽

Mexico City ◽

The United States ◽

Salmonella Typhi ◽

Resistance Pattern ◽

Chloramphenicol Resistance ◽

R Factor

SUMMARYA case of typhoid fever caused bySalmonella typhioccurred in Geneva. The patient was probably infected in Mexico City. The strain isolated from this patient corresponds with the description of the MexicanS. typhistrain, since it is a degraded Vi-strain resistant to chloramphenicol, streptomycin, sulphonamides and tetracyclines. It carried anfi−transferable R factor with a CSSuT resistance pattern. It can be accepted that this case forms part of the Mexican outbreak of chloramphenicol-resistant typhoid fever which has already been observed in visitors to Mexico from England and the United States.

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Typhoid Fever in the US Pediatric Population, 1999–2015: Opportunities for Improvement

Clinical Infectious Diseases ◽

10.1093/cid/ciaa914 ◽

2020 ◽

Cited By ~ 1

Author(s):

Jarred McAteer ◽

Gordana Derado ◽

Michael Hughes ◽

Amelia Bhatnagar ◽

Felicita Medalla ◽

...

Keyword(s):

United States ◽

Antimicrobial Resistance ◽

Typhoid Fever ◽

Antimicrobial Susceptibility ◽

Pediatric Population ◽

The United States ◽

International Travel ◽

Typhoid Vaccine ◽

Illness Onset ◽

New Public Health

Abstract Background Typhoid fever in the United States is acquired primarily through international travel by unvaccinated travelers. There is currently no typhoid vaccine licensed in the United States for use in children <2 years. Methods We reviewed Salmonella enterica serotype Typhi infections reported to the Centers for Disease Control and Prevention (CDC) and antimicrobial-resistance data on Typhi isolates in CDC’s National Antimicrobial Resistance Monitoring System from 1999 through 2015. Results 5131 cases of typhoid fever were diagnosed and 5004 Typhi isolates tested for antimicrobial susceptibility. Among 1992 pediatric typhoid fever patients, 1616 (81%) had traveled internationally within 30 days of illness onset, 1544 (81%) of 1906 were hospitalized (median duration, 6 days; range, 0–50), and none died. Forty percent (799) were <6 years old; 12% were <2 years old. Based on age and travel destination, 1435 (83%) of 1722 pediatric patients were vaccine-eligible; only 68 (5%) of 1361 were known to be vaccinated. Of 2003 isolates tested for antimicrobial susceptibility, 1216 (61%) were fluoroquinolone-nonsusceptible, of which 272 (22%) were also resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole (multidrug-resistant [MDR]). All were susceptible to ceftriaxone and azithromycin. MDR and fluoroquinolone-nonsusceptible isolates were more common in children than adults (16% vs 9%, P < .001, and 61% vs 54%, P < .001, respectively). Fluoroquinolone nonsusceptibility was more common among travel-associated than domestically acquired cases (70% vs 17%, P < .001). Conclusions Approximately 95% of currently vaccine-eligible pediatric travelers were unvaccinated, and antimicrobial-resistant infections were common. New public health strategies are needed to improve coverage with currently licensed vaccines. Introduction of an effective pretravel typhoid vaccine for children <2 years could reduce disease burden and prevent drug-resistant infections.

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Antimicrobial resistance in Salmonella that caused foodborne disease outbreaks: United States, 2003–2012

Epidemiology and Infection ◽

10.1017/s0950268816002867 ◽

2016 ◽

Vol 145 (4) ◽

pp. 766-774 ◽

Cited By ~ 12

Author(s):

A. C. BROWN ◽

J. E. GRASS ◽

L. C. RICHARDSON ◽

A. L. NISLER ◽

A. S. BICKNESE ◽

...

Keyword(s):

United States ◽

Antimicrobial Resistance ◽

Disease Outbreaks ◽

The United States ◽

Food Group ◽

Multidrug Resistant ◽

Antimicrobial Treatment ◽

Foodborne Disease ◽

Susceptibility Data ◽

Invasive Infections

SUMMARYAlthough most non-typhoidal Salmonella illnesses are self-limiting, antimicrobial treatment is critical for invasive infections. To describe resistance in Salmonella that caused foodborne outbreaks in the United States, we linked outbreaks submitted to the Foodborne Disease Outbreak Surveillance System to isolate susceptibility data in the National Antimicrobial Resistance Monitoring System. Resistant outbreaks were defined as those linked to one or more isolates with resistance to at least one antimicrobial drug. Multidrug resistant (MDR) outbreaks had at least one isolate resistant to three or more antimicrobial classes. Twenty-one per cent (37/176) of linked outbreaks were resistant. In outbreaks attributed to a single food group, 73% (16/22) of resistant outbreaks and 46% (31/68) of non-resistant outbreaks were attributed to foods from land animals (P < 0·05). MDR Salmonella with clinically important resistance caused 29% (14/48) of outbreaks from land animals and 8% (3/40) of outbreaks from plant products (P < 0·01). In our study, resistant Salmonella infections were more common in outbreaks attributed to foods from land animals than outbreaks from foods from plants or aquatic animals. Antimicrobial susceptibility data on isolates from foodborne Salmonella outbreaks can help determine which foods are associated with resistant infections.

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Need for Annual Surveillance of Antimicrobial Resistance in Streptococcus pneumoniae in the United States: 2-Year Longitudinal Analysis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.45.4.1037-1042.2001 ◽

2001 ◽

Vol 45 (4) ◽

pp. 1037-1042 ◽

Cited By ~ 94

Author(s):

Daniel F. Sahm ◽

James A. Karlowsky ◽

Laurie J. Kelly ◽

Ian A. Critchley ◽

Mark E. Jones ◽

...

Keyword(s):

United States ◽

Streptococcus Pneumoniae ◽

Antimicrobial Resistance ◽

Antimicrobial Agents ◽

The United States ◽

Multidrug Resistant ◽

Fluoroquinolone Resistance ◽

Resistance Patterns ◽

Changing Patterns ◽

Resistance To Penicillin

ABSTRACT Although changing patterns in antimicrobial resistance inStreptococcus pneumoniae have prompted several surveillance initiatives in recent years, the frequency with which these studies are needed has not been addressed. To approach this issue, the extent to which resistance patterns change over a 1-year period was examined. In this study we analyzed S. pneumoniaeantimicrobial susceptibility results produced in our laboratory with isolates obtained over 2 consecutive years (1997–1998 and 1998–1999) from the same 96 institutions distributed throughout the United States. Comparison of results revealed increases in resistant percentages for all antimicrobial agents studied except vancomycin. For four of the agents tested (penicillin, cefuroxime, trimethoprim-sulfamethoxazole, and levofloxacin), the increases were statistically significant (P < 0.05). Resistance to the fluoroquinolone remained low in both years (0.1 and 0.6%, respectively); in contrast, resistance to macrolides was consistently greater than 20%, and resistance to trimethoprim-sulfamethoxazole increased from 13.3 to 27.3%. Multidrug resistance, concurrent resistance to three or more antimicrobials of different chemical classes, also increased significantly between years, from 5.9 to 11%. The most prevalent phenotype was resistance to penicillin, azithromycin (representative macrolide), and trimethoprim-sulfamethoxazole. Multidrug-resistant phenotypes that included fluoroquinolone resistance were uncommon; however, two phenotypes that included fluoroquinolone resistance not found in 1997–1998 were encountered in 1998–1999. This longitudinal surveillance study of resistance inS. pneumoniae revealed that significant changes do occur in just a single year and supports the need for surveillance at least on an annual basis, if not continuously.

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