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Letter
Antimicrobial Drug–resistant
Salmonella Typhimurium (Reply to Dahl)
Read original article,
http://www.cdc.gov/ncidod/EID/vol8no5/01-0267.htm
Read Dahl's article,
http://www.cdc.gov/ncidod/EID/vol9no10/02-0716.htm
Morten Helms,* Pernille Vastrup,* and Kåre Mølbak*
*Statens Serum Institut, Copenhagen, Denmark
Suggested citation
for this article: Helms M, Vastrup P, Mølbak K. Antimicrobial
drug-resistant Salmonella Typhimurium (reply to Dahl). Emerg
Infect Dis [serial online] 2003 Oct [date cited]. Available from:
URL: http://www.cdc.gov/ncidod/EID/vol9no10/03-0029.htm
In Reply to Dahl: The emergence and spread of multidrug-resistant
Salmonella enterica serovar Typhimurium DT104 (MDR DT104) contributed
to an international increase in antimicrobial drug resistance in S.
Typhimurium in the late 1990s (1,2). This type of Salmonella
is usually resistant to five drugs: ampicillin, chloramphenicol, streptomycin,
sulfonamides, and tetracycline (R-type ACSSuT) and easily acquires resistance
to other drugs, including quinolones, trimethoprim, and aminoglycosides
(1,3–5). To determine death rates after infection with
MDR DT104 or closely related strains, we identified patients who were
infected with strains at least resistant to ACSSuT (6).
Analysis limited to strains that were only R-type ACSSuT would have given
a misleading result since MDR DT104 often, as mentioned, develops additional
resistance to other classes of antimicrobial drugs in addition to the
ACSSuT-complex. This fact needs to be taken into account in any attempt
to quantify the overall public health impact of MDR DT104 and related
strains.
We found, in our matched cohort study (6), that 283
patients infected with strains resistant to at least ACSSuT were 4.8 times
more likely to die than the general Danish population, compared with 2.3
for 953 patients infected with pansusceptible strains. This difference
in death rates ocurred mainly because 40 of the 283 strains had R-type
ACSSuTNx (i.e., additional resistance to nalidixic acid), and infection
with this strain in particular is associated with a high death rate (relative
mortality 13.1). As Dahl suggests, infection with R-type ACSSuT (Nx susceptible)
was not associated with excess mortality in the 243 patients included
in the analysis, and the measured effect of ACSSuT was achieved by the
inclusion of the nalidixic acid–resistant strains in this group. However,
all deaths associated with nalidixic acid–resistant strains occurred in
the 40 patients with R-type ACSSuTNx (being DT104s), whereas none of the
43 patients infected with non-ACSSuT strains resistant to nalidixic acid
died. This finding may be related to small numbers in these subanalyses.
However, because 25 of the patients with R-type ACSSuTNx were part of
an outbreak, they may have had an average higher exposure dose, which
may have contributed to some deaths (3). In addition,
an interaction between different resistance traits in Salmonella may exist,
which may lead to more deaths and disease, or DT104 may be somewhat more
virulent than most other S. Typhimurium subtypes.
The database that we used for our analysis was updated in May 2002. We
have now identified 13 deaths in 342 patients infected with strains resistant
to ACSSuT (but Nx susceptible), which corresponds to a relative mortality
rate of 4.18 (95% confidence interval [CI]) 2.18 to 8.02) compared with
a matched sample of the general population. Of 1,432 patients infected
with pansusceptible strains, 43 patients died (relative mortality rate
2.64; 95% CI 1.88 to 3.70). In other words, the mortality rate in patients
infected with strains resistant to ACSSuT (Nx susceptible) was 1.6 times
higher than in patients with pansusceptible strains (p value for homogeneity
0.22). These estimates were not adjusted for coexisting conditions as
were the estimates in the paper (6).
We agree with Dahl that particular problems are associated with quinolone
resistance in zoonotic salmonellae and that fluoroquinolones may have
reduced efficacy to treat patients infected with Salmonella strains
that are nalidixic acid (quinolone) resistant (7). We
therefore encourage initiatives to preserve the efficacy of fluoroquinolones,
including a limitation of their use in agriculture. Whether infection
with S. Typhimurium R-type ACSSuT, with no additional resistance,
is associated with higher disease or death rates than pansusceptible S.
Typhimurium remains unclear. Although the difference was not significant
(p=0.22), our recent estimates suggest that the death rate is approximately
60% higher in patients infected with such strains. This view is corroborated
by recent studies from the United States, which suggest that S.
Typhimurium R-type ACSSuT is associated with an increased risk for blood
stream infection (8) and that resistance in nontyphoid
Salmonella is associated with an increased risk for admission to
hospital (9).
References
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spectrum of resistance in multiresistant Salmonella Typhimurium.
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increased hospitalization; NARMS 1996-2000. Proceedings of the International
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