26 THE NATIONAL MEDICAL JOURNAL OF INDIA VOL. 26, NO. 1, 2013
All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029,
India
S. SOOD, N. MAHAJAN, R. VERMA Department of Microbiology
V.K. SHARMA Department of Dermatology and Venereology
Postgraduate Institute of Medical Education and Research,
Dr R.M.L. Hospital, New Delhi 110001, India
H.K. KAR Department of Dermatology, STD and Leprosy
Correspondence to S. SOOD; seemalsood@rediffmail.com
© The National Medical Journal of India 2013
Emergence of decreased susceptibility to
extended-spectrum cephalosporins in
Neisseria gonorrhoeae in India
S. SOOD, N. MAHAJAN, R. VERMA, H.K. KAR,
V.K. SHARMA
ABSTRACT
Background. In the past, Neisseria gonorrhoeae has
developed resistance to antimicrobial agents used for its
treatment. Consequently, extended-spectrum cephalosporins
form the mainstay of treatment for gonorrhoea.
Methods. Samples from 88 patients attending the sexually
transmitted diseases clinics from December 2009 to January
2011 in two referral hospitals in New Delhi were studied.
Antimicrobial susceptibility testing was done using the disc
diffusion method as per the calibrated dichotomous sensitivity
technique against the following antibiotics: penicillin (0.5 i.u.),
tetracycline (10 µg), nalidixic acid (30 µg), ciprofloxacin (1
µg), spectinomycin (100 µg), ceftriaxone (0.5 µg) and
cefpodoxime (10 µg) (Oxoid UK). Azithromycin (15 µg)
(Oxoid, UK) was tested as per the guidelines of the Clinical
and Laboratory Standards Institute. Minimum inhibitory
concentrations were determined using the Etest for penicillin,
tetracycline, ciprofloxacin, ceftriaxone, spectinomycin and
azithromycin as per the manufacturer’s instruction (Biomerieux,
France).
Results. Eighteen isolates of Neisseria gonorrhoeae were
obtained. Three of these had decreased susceptibility to ceftria-
xone and cefpodoxime by the disc diffusion method. The mini-
mum inhibitory concentrations of ceftriaxone for two isolates
were 0.064 µg/ml and for one isolate it was 0.125 µg/ml.
Conclusion. Higher minimum inhibitory concentrations to
extended-spectrum cephalosporins is of concern as it has been
shown to precede treatment failure. This may warrant its use in
increased/multiple dosages alone or possibly in combination
(dual therapy), thereby complicating effective disease control.
Our report is in accordance with earlier reports from different
parts of the world. Therefore, a continuous surveillance of
antimicrobial resistance is crucial to tailor treatment schedules
for Neisseria gonorrhoeae in a particular geographical region.
Natl Med J India 2013;26:26–8
INTRODUCTION
The prevention and control of gonorrhoea is an important public
health concern due to the high burden of disease, the recent
increase in reported rates of infection and the reproductive and
economic consequences of infection.
1–3
In the absence of a vaccine,
the control of gonorrhoea is achieved through effective
antimicrobial therapy to eradicate the infection, reduce transmission
and also prevent complications. The unrestricted access to anti-
microbials, inappropriate selection, overuse of antibiotics and
suboptimal quality of antibiotics, as well as genetic mutations
within the organism have contributed to the development of
antibiotic resistance in Neisseria gonorrhoeae.
3
The organism has
been reported to develop resistance to multiple classes of
antimicrobials including penicillins, tetracyclines and quinolones;
and these are not used in many parts of the world.
4
Even the more
recently available macrolides now have limited utility, leaving
extended-spectrum cephalosporins (ESCs, both oral and injectable)
and spectinomycin (when and where it is available) as the mainstay
of treatment.
5
Though there is no report of treatment failure with ESCs from
India, there are reports of treatment failure due to oral cephalosporins
(cefixime and ceftibuten) in genital tract gonorrhoea from Japan,
Hong Kong, Norway, United Kingdom and Austria.
4,6–9
Also,
pharyngeal gonococcal isolate with a high-level of resistance to
ceftriaxone has been reported (the last remaining option for
empirical first-line treatment) from Japan.
10
Furthermore, elevated
minimum inhibitory concentrations (MICs) to cephalosporins
have been reported from Japan, Australia, China, Hong Kong,
USA, various parts of Europe and India.
11,12
A worldwide
continuous surveillance of gonococcal antimicrobial resistance
and treatment failures is crucial to minimize the spread of ESC-
resistant gonococcal strains to ensure that gonorrhoea remains a
treatable infection.
9
Hence, we determined the antimicrobial
susceptibility pattern of N. gonorrhoeae isolates in our population.
METHODS
Between December 2009 and January 2011, 47 women with
cervicitis and 41 men with urethritis in the age group 15–50 years
presenting as outpatients to the Dermatology departments of the
All India Institute of Medical Sciences (AIIMS) and Ram Manohar
Lohia Hospital, New Delhi were included in the study. Urethral
swabs were collected from men and endocervical swabs from
women by a physician as per the standard protocol. Culture was
done on standard culture media; modified Thayer Martin (GC
agar base plus VCNT (A) inhibitors) (Himedia, India) and chocolate
agar (Columbia agar base [BD BBL, USA] plus sheep blood) at
the bedside. The suspected isolates from culture were
presumptively identified by Gram-stain, oxidase test and superoxol
test, and confirmed by rapid carbohydrate utilization test (RCUT)
as per the standard protocol.
13
The confirmed colonies were used
to determine the antimicrobial susceptibility pattern of the isolates
and were also tested for beta-lactamase production.
Antimicrobial susceptibility testing was done using the disc
diffusion method as per the Calibrated Dichotomous Sensitivity
(CDS) technique against the following antibiotics: penicillin
(0.5 i.u.), tetracycline (10 µg), nalidixic acid (30 µg), ciprofloxacin
(1 µg), spectinomycin (100 µg), ceftriaxone (0.5 µg) and cefpo-
doxime (10 µg) (Oxoid, UK).
14
It uses a uniform zone size to
define susceptible strains with the results being interpreted in
terms of annular radius (mm). For tetracycline, those strains with
MIC >16 µg/ml as determined by the disc diffusion method
were described as plasmid-mediated tetracycline-resistant
N. gonorrhoeae (TRNG). The chromosomally-mediated resistance
to tetracycline has to be detected by the MIC method. For
ceftriaxone, strains with annular radius of 5–9 mm and MIC of