Keddy garp sa 0

Evolving antimicrobial resistance in enteric pathogens Karen H. Keddy Enteric Diseases Reference Unit National Institute for Communicable Diseases National Health Laboratory Service

GERMS-SA • National active laboratory-based surveillance: microbiology reference units of NICD since 2003. • All diagnostic microbiology laboratories in South Africa are encouraged to submit isolates from patients fulfilling relevant case definition. • Data supplemented by audits are conducted wherever possible to identify missing cases, which are then included in the database.

Enteric Diseases Reference Unit • Salmonella species, including Salmonella Typhi and NTS. • Vibrio cholerae, specifically V. cholerae O1.

• Shigella species • Diarrhoeagenic Escherichia coli, including EHEC. • Campylobacter (from 2010)

Salmonella Typhi 100%

100%

90%

90%

80%

80%

70%

70%

60%

60% Resistant Intermediate Sensitive

50%

40%

40%

30%

30%

20%

20%

10%

10%

0%

Resistant Intermediate Sensitive

50%

0% 2003

2004

2005

2006

2007

2008

2009

2003

2004

2005

AMPICILLIN

2006

2007

2008

2009

CHLORAMPHENICOL

100%

100%

90%

90%

80%

80%

70%

70%

60%

60% Resistant Intermediate Sensitive

50%

40%

40%

30%

30%

20%

20%

10%

10%

0%

Resistant Intermediate Sensitive

50%

0% 2003

2004

2005

2006 NALIDIXIC ACID

2007

2008

2009

2003

2004

2005

2006 CIPROFLOXACIN

2007

2008

2009

Quinolone resistance: Salmonella Typhi • 6% of isolates between 2003 & 2009 (n=629).

• 20% of isolates in 2009 (n=60).

• 2003-2007*: -All isolates were negative by PCR screening for qnr genes -All isolates amino-acid mutations in both GyrA and ParC. -Mutations in GyrA and ParC in combination with active efflux of antibiotic out of the bacterial cell. *Smith et al, Epidemiol Infect 2010

FQ resistance: Salmonella Typhi • 65 y/o Cape Town resident – contact from Bangladesh.

• Ciprofloxacin MIC: 4 µg/ml.

• Single amino-acid mutation in GyrA (Ser83 to Tyr) with the QnrS1 protein and active efflux*.

• Plasmid mediated quinolone resistance co-transferred from Salmonella Typhi with ESBL production†. *Keddy et al, submitted †Pfeifer

et al, EID 2009

Non-typhoidal Salmonella 100%

100%

90%

90%

80%

80%

70%

70%

60%

60% Resistant Intermediate Sensitive

50%

40%

40%

30%

30%

20%

20%

10%

10%

0%

Resistant Intermediate Sensitive

50%

0% 2003

2004

2005

2006

2007

2008

2009

2003

AMPICILLIN

90%

80%

70%

60% Resistant Intermediate Sensitive

50%

40%

30%

20%

10%

0% 2004

2005

2006 SULPHAMETHOXAZOLE

2005

2006 CHLORAMPHENICOL

100%

2003

2004

2007

2008

2009

2007

2008

2009

Non-typhoidal Salmonella 100%

100%

90%

80%

80%

70%

60%

60% Resistant Intermediate Sensitive

40%

Resistant Intermediate Sensitive

50%

40%

30%

20%

20%

10%

0%

0% 2003

2004

2005

2006

2007

2008

2009

2003

NALIDIXIC ACID

80%

60% Resistant Intermediate Sensitive 40%

20%

0% 2004

2005

2006 CEFTRIAXONE

2005

2006 CIPROFLOXACIN

100%

2003

2004

2007

2008

2009

2007

2008

2009

NTS ESBL production • Specific Salmonella serotypes more commonly affected.

• Strong association with nosocomial isolates.

• TEM63 & TEM131* and CTX-M37†. *Kruger et al, AAC 2004 †Govinden

et al, Int J Antimicrob Agents 2009

NTS Quinolone and FQ Resistance • Nosocomial association (MDR).

• Chromosomally (gyrA/B; parC/E)* and plasmid (qnr) mediated†.

*Govinder, MSc 2009 †Govinder

et al, JMM 2009

NTS Role of antimicrobials in environment • Not studied in RSA context.

• Evidence of common Salmonella Typhimurium strains circulating among humans and animals*.

• Initial research being undertaken.

• Role of antimicrobial therapy for STIs? *Dwarika, MSc 2009

Shigella 100%

100%

90%

80%

80%

70%

60%

60% Resistant Intermediate Sensitive

50%

40%

Resistant Intermediate Sensitive 40%

30%

20%

20%

10%

0%

0% 2003

2004

2005

2006

2007

2008

2009

2003

2004

2005

AMPICILLIN

2006

2007

2008

2009

CHLORAMPHENICOL

100%

100%

90%

90%

80%

80%

70%

70%

60%

60% Resistant Intermediate Sensitive

50%

40%

40%

30%

30%

20%

20%

10%

10%

0%

Resistant Intermediate Sensitive

50%

0% 2003

2004

2005

2006 SULPHAMETHOXAZOLE

2007

2008

2009

2003

2004

2005

2006 TETRACYCLINE

2007

2008

2009

Shigella 100%

100%

90%

90%

80%

80%

70%

70%

60%

60% Resistant Intermediate Sensitive

50%

40%

40%

30%

30%

20%

20%

10%

10%

0%

Resistant Intermediate Sensitive

50%

0% 2003

2004

2005

2006

2007

2008

2009

2003

NALIDIXIC ACID

80%

60% Resistant Intermediate Sensitive 40%

20%

0% 2004

2005

2006 CEFTRIAXONE

2005

2006 CIPROFLOXACIN

100%

2003

2004

2007

2008

2009

2007

2008

2009

Shigella resistance • Isolates primarily from stool.

• Resistance to 1st line antibiotics constant.

• Resistance to quinolones and FQ cause for concern.

• ESBL production possibly noscomial association.

• Role of oral 3rd generation cephalosporins for STIs?

Acknowledgments • GERMS-SA – PIs, SOs, laboratory staff & support staff.

• Funders: - Centers for Disease Control.

- MRC - NHLS - RT