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Published Date: 2011-10-31 12:42:56
Subject: PRO/EDR> Antibiotic resistance, Salmonella typhi - India: (Mumbai) fluoroquinolones
Archive Number: 20111031.3235

ANTIBIOTIC RESISTANCE, SALMONELLA TYPHI - INDIA: (MUMBAI)
FLUOROQUINOLONES
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Date: Thu 27 Oct 2011
Source: DNA (Daily News & Analysis) [edited]
http://www.dnaindia.com/mumbai/report_more-typhoid-cases-land-in-hospitals_1603881

Come the time of indulgence and typhoid rears its ugly head. This
festival season is no different. Worse, about 70 percent of [Mumbai]
city residents suffering from it are not responding to oral medication
and have had to be hospitalised.

Dr Pratit Samdhani, consulting physician at the Jaslok Hospital, said,
"Of the typhoid cases treated in the last few months, 70-80 percent
have shown high resistance towards drugs from the quinoline family
that are given orally. So, many had to be hospitalised for intravenous
treatment."

Dr Anil Ballani, consulting physician at the Lilavati Hospital,
agreed. "The severity of typhoid has increased of late. We have to
hospitalise patients because they are not responding to oral drugs.
These are culture-positive typhoid cases caused by the salmonella bug
[_Salmonella enterica_ serovar Typhi, also called _Salmonella typhi_].
Some take more than 5 days of hospitalisation and most of them
initially don't respond to even IV antibiotic treatment."

Dr Khusrav Bhajan, intensivist of the PD Hinduja Hospital, said the
trend has been consistent across the city. "In most of these cases,
the fever does not subside for the 1st 10 days." Over 100 people
sought admission in several hospitals for typhoid this month but
private doctors say the "numbers are under-reported".

Doctors' orders: keep a watch on what you dig your teeth into. Dr ND
Moulick, head of the Sion Hospital, said, "People need to maintain
levels of hygiene. Eat healthy food. It is wise to stay off street
food. Eating contaminated food can lead to diarrhoea, vomiting,
gastroenteritis, and jaundice."

There has also been a rise in the number of cases of gastroenteritis
and viral fever in the city following the receding of the monsoon.

[Byline: Somita Pal]

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[Although unusual in the United States, typhoid fever caused by
_Salmonella enterica_ serovar Typhi, also called _Salmonella typhi_,
remains common in many developing countries. In the United States
about 400 cases of typhoid fever occur each year, and 75 percent of
these cases are acquired while traveling abroad
(http://www.cdc.gov/nczved/divisions/dfbmd/diseases/typhoid_fever/),
mainly to southern Asia
(http://wwwnc.cdc.gov/eid/article/17/6/10-0594_article.htm).
Fluoroquinolones, such as ciprofloxacin, orally or intravenously, or
ceftriaxone intravenously have been the drugs of choice for treatment
of typhoid fever. Azithromycin is an alternative. However,
ciprofloxacin resistance is an increasing problem, especially in the
Indian subcontinent and Southeast Asia.

Mechanisms responsible for resistance to fluoroquinolones in _S.
typhi_ are mainly: mutations in the quinolone resistance-determining
region (QRDR) of the genes that encode DNA gyrase or topoisomerase IV,
which decrease their binding affinity to fluoroquinolones, and thereby
decrease the drugs' effectiveness; and efflux pumps that decrease
intracellular fluoroquinolone concentration
(http://www.im.microbios.org/1301/IM1301_0015.pdf). Plasmid-mediated
fluoroquinolone resistance genes have been described in non-typhi
salmonella (http://aac.asm.org/cgi/reprint/53/5/2142 and
http://wwwnc.cdc.gov/eid/article/16/11/10-0464_article.htm). The
plasmid-mediated fluoroquinolone resistance _qnr_ gene encodes
proteins that can bind to DNA gyrase, protecting it from the action of
fluoroquinolones. QepA is a plasmid-encoded efflux pump that
significantly affects susceptibility to norfloxacin and aac(6')-Ib-cr
is a modified aminoglycoside N-acetyltransferase that acetylates some
fluoroquinolones, including ciprofloxacin.

Treatment failures with fluoroquinolones are commonly reported from
South 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 strains. An increased risk for fluoroquinolone treatment
failure has been demonstrated in typhoid fever from strains of _S.
typhi_ with decreased susceptibility to ciprofloxacin (minimum
inhibitory concentration or MICs 0.125 to 1 mg/L)
(http://wwwnc.cdc.gov/eid/article/17/6/10-0594_article.htm). The
ciprofloxacin MICs of these isolates nevertheless are considered to be
in the susceptible range. In vitro resistance to nalidixic acid has
been used to predict reduced susceptibility to ciprofloxacin in vitro
in these isolates. However, isolates have been reported, mainly from
South Asia, that have reduced susceptibility to ciprofloxacin (MICs
0.125-1.0 mg/L), but are susceptible to nalidixic acid
(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1539082/?tool=pmcentrez).

In addition, strains resistant to both nalidixic acid and
ciprofloxacin (MICs greater than 4 mg/L), some of which are also
resistant to ceftriaxone, have been reported from India (Kownhar H,
Shankar EM, Rajan R, Rao UA: Emergence of nalidixic acid-resistant
_Salmonella enterica_ serovar Typhi resistant to ciprofloxacin in
India. J Med Microbiol 2007; 56(Pt.1): 136-7
http://jmm.sgmjournals.org/content/56/1/136.full; Capoor MR, Nair D,
Deb M, Aggarwal P: Enteric fever perspective in India: emergence of
high-level ciprofloxacin resistance and rising MIC to cephalosporins.
J Med Microbiol 2007; 56(Pt.8): 1131-2
http://jmm.sgmjournals.org/content/56/8/1131.long). 9
ciprofloxacin-resistant (MICs greater than 4 mg/L) and nalidixic
acid-resistant (MICs greater than 32 mg/L) _S. enterica_ serotype
Typhi isolates have been detected in the United States during
1999-2008
(http://wwwnc.cdc.gov/eid/article/17/6/10-0594_article.htm). All
were susceptible to ceftriaxone. 8 of the 9 patients had traveled to
India within 30 days before illness onset.

Typhoid fever caused by _S. typhi_ is not a zoonotic disease. _S.
typhi_ is transmitted only from human to human and prevention of its
transmission involves stopping human fecal contamination of food and
drinking water. Endemic antibiotic resistance among _S. typhi_ in
developing countries emphasizes the importance of ensuring food
safety, safe water, sanitary disposal of human excrement, and
immunization in these countries.

A HealthMap/ProMED-mail interactive map of India, showing the location
of Mumbai, can be accessed at http://healthmap.org/r/1iZ2. - Mod.ML]

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