Determination of the antimicrobial susceptibility of Neisseria gonorrhoeae

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Determination of the antimicrobial
susceptibility of Neisseria gonorrhoeae

• Trevor Winstanley Rebecca Clarke
• Department of Microbiology
• Royal Hallamshire Hospital
• Sheffield UK

29 July 2003
Freeman Hospital
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Gonorrhoea

• 2nd most common bacterial STD
• gt 22,500 episodes diagnosed in GUM clinics in
  England Wales (2001)
• Highest incidence
• Males 20-24 256/100,000
• Females 16-19 198/100,000

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Epidemiology

• Concentrated within demographic and behavioural
  risk groups
• High-levels of
• re-infection
• concurrent STDs
• asymptomatic infection

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Public health concern

• Increasing incidence
• Poor reproductive and sexual health outcomes
• High prevalence of resistance
• onward transmission
• adverse clinical sequelae

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Antimicrobial resistance

• 10 -12 of gonococcal isolates are resistant to
  some degree
• inner cities
• those acquiring infections abroad
• gay and bisexual men

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Plasmid-mediated
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Chromosomal
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Chromosomal
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U.K. guidelines

• Easily treatable
• 95 cure from 1st line therapy
• Penicillins
• Fluoroquinolones
• ciprofloxacin, ofloxacin
• Cephalosporins
• ceftriaxone, cefixime
• (Doxycycline / tetracycline)

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GRASP

• Gonococcal Resistance to Antimicrobials
  Surveillance Programme
• DoH sentinel surveillance
• PHLS Communicable Disease Surveillance Centre
  (CDSC)
• PHLS Genitourinary Infections Reference
  Laboratory (GUIRL)
• Department of Infectious Diseases Microbiology
  at Imperial College

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GRASP 2001 (n 2666)
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Cure rates

• Uncomplicated genital gonorrhoea
• Recommended dosage
• Susceptible gt 95
• Intermediate 90-95
• Resistant lt 90
• WHO SRGA
  NCCLS

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Media

• NCCLS
• SRGA
• BSAC
• ARMRL
• GRASP

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Objectives

• To validate the BSAC disc diffusion method for
  N.gonorrhoeae
• to translate reference into routine
• To confirm or refute tentative breakpoints
• To extend the range of interpretive criteria

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Methodology

• 222 distinct isolates from 5 geographical regions
• 5 WHO control strains
• Disc diffusion tests, MICs
• BSAC methodology
• ß-lactamase
• Nitrocefin

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Penicillin
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Amoxycillin
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Co-amoxyclav
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Ciprofloxacin
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Nalidixic acid
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Tetracycline
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Metzler DeHaan analysis
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The MIC breakpoint has been lowered to ensure
that isolates with reduced susceptibility to
ciprofloxacin are detected.
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Quinolone resistance is most reliably detected
with nalidixic acid. Strains with reduced
susceptibility to fluoroquinolones have no zone
of inhibition with nalidixic acid.
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Test for ?-lactamase.
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Resistance to ceftriaxone has not been described.
Isolates with chromosomally encoded penicillin
resistance (low level) have slightly reduced
zones of inhibition with ceftriaxone but remain
susceptible. Confirm by MIC.
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Use tetracycline result to infer susceptibility
to doxycycline. Isolates with plasmid-mediated
resistance have no zones of inhibition and those
with low-level chromosomal resistance have zones
14-26 mm
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Next?

• Cefixime

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Clap!