Antimicrobial Drug-resistant Salmonella Typhimurium (Reply to Helms) by yew20072



    infection in Mexico, 1980. Am J Epidemiol
                                                           ant S. Typhimurium (1). In this letter,               Antimicrobial
                                                           the Table is based on the original
                                                           table. However, two additional com-                  Drug–resistant
Address for correspondence: Jayanton
                                                           parisons have been added: the p val-                   Salmonella
Patumanond, Department of Community
                                                           ues, which are not based on the data
Medicine, Faculty of Medicine, Chiang Mai
                                                           but are approximations based on the
University, Chiang Mai 50200, Thailand; fax:
                                                           parameters in the table.                             (Reply to Dahl)
66+53+945476; email:
                                                              The conclusion is that only                      In Reply to Dahl: The emergence
                                                           quinolone resistance is associated              and spread of multidrug-resistant
                                                           with excess mortality compared with             Salmonella        enterica      serovar
                                                           nonresistant isolates. Penta-resistant,         Typhimurium DT104 (MDR DT104)
                                                           quinolone-susceptible S. Typhim-                contributed to an international
                                                           urium has a risk ratio of 2.9 (1.1 to           increase in antimicrobial drug resist-
      Antimicrobial                                        7.9) compared to the ratio of                   ance in S. Typhimurium in the late
     Drug–resistant                                        non–penta-resistant isolates 2.1 (1.5           1990s (1,2). This type of Salmonella
                                                           to 2.9). When these figures are com-
       Salmonella                                          pared, the approximate p value is
                                                                                                           is usually resistant to five drugs:
                                                                                                           ampicillin, chloramphenicol, strepto-
      Typhimurium                                          0.55, which, of course, is far from             mycin, sulfonamides, and tetracycline
    (Reply to Helms)                                       being significant. Thus, on the basis           (R-type ACSSuT) and easily acquires
                                                           of the article by Helms, penta resist-          resistance to other drugs, including
   In Reply to Helms: In the article                       ance may not pose a greater threat to           quinolones, trimethoprim, and amino-
by Helms et al., Helms concludes that                      human health than non–penta resist-             glycosides (1,3–5). To determine
infections with Salmonella Typhim-                         ance. However, the measured effect of           death rates after infection with MDR
urium strains resistant to ampicillin,                     penta resistance is achieved by the             DT104 or closely related strains, we
chloramphenicol, streptomycin, sul-                        inclusion of quinolone-resistant S.             identified patients who were infected
fonamide, and tetracycline (hereafter                      Typhimurium in the group.                       with strains at least resistant to
referred to as penta-resistant) were                                                                       ACSSuT (6). Analysis limited to
associated with higher death rates than                                    Jan Dahl*
                                                                                                           strains that were only R-type ACSSuT
infections with non–penta-resistant S.                     *Danish Bacon and           Meat     Council,
                                                                                                           would have given a misleading result
Typhimurium. Helms also concluded                          Copenhagen, Denmark
                                                                                                           since MDR DT104 often, as men-
that infections with quinolone-resist-                                                                     tioned, develops additional resistance
ant (nalidixine-resistant) S. Typhimu-                     Reference
                                                                                                           to other classes of antimicrobial drugs
rium were associated with higher                            1. Helms M, Vastrup P, Gerner-Smidt P,         in addition to the ACSSuT-complex.
death rates than quinolone-susceptible                         Mølbak K. Excess mortality associated
                                                                                                           This fact needs to be taken into
S. Typhimurium (1).                                            with     antimicrobial  drug-resistant
                                                               Salmonella Typhimurium. Emerg Infect        account in any attempt to quantify the
   Table 2 in Helms’ article provides                                                                      overall public health impact of MDR
                                                               Dis 2002;8:490–5.
information that enables close scruti-                                                                     DT104 and related strains.
ny of this conclusion and comparison                       Address for correspondence: Jan Dahl, Danish        We found, in our matched cohort
of the excess mortality associated                         Bacon and Meat Council, Axeltory 3, 1609        study (6), that 283 patients infected
with penta-resistant, quinolone-sus-                       Copenhagen V, Denmark; fax: 4533145756;         with strains resistant to at least
ceptible S. Typhimurium with the                           email:                   ACSSuT were 4.8 times more likely
excess mortality of non–penta-resist-                                                                      to die than the general Danish popula-
Table. Table showing additional comparisons (1)a                                                           tion, compared with 2.3 for 953
                            Resistant                                  Susceptible                         patients infected with pansusceptible
                   Deaths/                                      Deaths/                                    strains. This difference in death rates
                    cases       RRb (95% CI)                     cases     RRb (95 % CI)        p value
Penta with and     12/283      4.8 (2.2 to 10.5)                47/1,764   2.1 (1.5 to 2.9)      0.06
                                                                                                           ocurred mainly because 40 of the 283
without quinolone                                                                                          strains had R-type ACSSuTNx (i.e.,
Penta with          5/40      13.1 (3.3 to 51.9)                47/1,764    2.1 (1.5 to 2.9)c    0.01d     additional resistance to nalidixic
Penta without       7/243       2.9 (1.1 to 7.9)                47/1764     2.1 (1.5 to 2.9)c   0.55cd
                                                                                                           acid), and infection with this strain in
quinolone                                                                                                  particular is associated with a high
 RR, relative risk; CI, confidence interval.                                                               death rate (relative mortality 13.1). As
  Adjusted for coexisting conditions.
 Compared to the non-penta group.                                                                          Dahl suggests, infection with R-type
  Approximations based on the parameters from the table.                                                   ACSSuT (Nx susceptible) was not

1350                                         Emerging Infectious Diseases • Vol. 9, No. 10, October 2003

associated with excess mortality in the    (quinolone) resistant (7). We therefore             6. Helms M, Vastrup P, Gerner-Smidt P,
243 patients included in the analysis,     encourage initiatives to preserve the                  Mølbak K. Excess mortality associated
                                                                                                  with       antimicrobial      drug-resistant
and the measured effect of ACSSuT          efficacy of fluoroquinolones, includ-                  Salmonella typhimurium. Emerg Infect Dis
was achieved by the inclusion of the       ing a limitation of their use in agricul-              2002:8:490–5.
nalidixic acid–resistant strains in this   ture. Whether infection with S.                     7. Aarestrup FM, Wiuff C, Mølbak K,
group. However, all deaths associated      Typhimurium R-type ACSSuT, with                        Threlfall EJ. Is it time to change the break
                                                                                                  points for fluoroquinolones for Salmonella?
with nalidixic acid–resistant strains      no additional resistance, is associated                Antimicrob Agents Chemother 2003;47:
occurred in the 40 patients with R-        with higher disease or death rates than                827–9.
type ACSSuTNx (being DT104s),              pansusceptible S. Typhimurium                       8. Mølbak K, Varma J, Rossiter S, Lay J,
whereas none of the 43 patients infect-    remains unclear. Although the differ-                  Joyce K, Stamey K, et al. Antimicrobial
                                                                                                  resistance in Salmonella serotype
ed with non-ACSSuT strains resistant       ence was not significant (p=0.22), our                 Typhimurium, R-type ACSSuT, is associat-
to nalidixic acid died. This finding       recent estimates suggest that the death                ed with bacteremia; NARMS, 1996-2000.
may be related to small numbers in         rate is approximately 60% higher in                    Proceedings       of    the    International
these subanalyses. However, because        patients infected with such strains.                   Conference of Emerging Infectious
                                                                                                  Diseases, 2002 Mar 24–27, Atlanta,
25 of the patients with R-type             This view is corroborated by recent                    Georgia, USA. Available from: URL:
ACSSuTNx were part of an outbreak,         studies from the United States, which        
they may have had an average higher        suggest that S. Typhimurium R-type                  9. Varma JK, Mølbak K, Rossiter S, Hawkins
exposure dose, which may have con-         ACSSuT is associated with an                           MA, Jones TF, Mauvais SH, et al.
                                                                                                  Antimicrobial resistance in Salmonella is
tributed to some deaths (3). In addi-      increased risk for blood stream infec-                 associated with increased hospitalization;
tion, an interaction between different     tion (8) and that resistance in nonty-                 NARMS 1996-2000. Proceedings of the
resistance traits in Salmonella may        phoid Salmonella is associated with                    International Conference of Emerging
exist, which may lead to more deaths       an increased risk for admission to hos-                Infectious Diseases, 2002 Mar 24–27,
                                                                                                  Atlanta, Georgia, USA. Available from:
and disease, or DT104 may be some-         pital (9).                                             URL:
what more virulent than most other S.
Typhimurium subtypes.                       Morten Helms,* Pernille Vastrup,*                 Address for correspondence. Kåre Mølbak,
    The database that we used for our              and Kåre Mølbak*                           Department of Epidemiology, Statens Serum
analysis was updated in May 2002.          *Statens Serum Institut, Copenhagen,               Institut, Artillerivej 5, DK-2300 Copenhagen S,
We have now identified 13 deaths in        Denmark
                                                                                              Denmark; fax: 45 3268 3874; email:
342 patients infected with strains                                                  
resistant to ACSSuT (but Nx suscepti-      References
ble), which corresponds to a relative       1. Threlfall EJ, Frost JA, Ward LR, Rowe B.
mortality rate of 4.18 (95% confi-             Increasing spectrum of resistance in mul-
dence interval [CI]) 2.18 to 8.02)             tiresistant Salmonella Typhimurium.
                                               Lancet 1996;347:1053–4.
compared with a matched sample of           2. Glynn MK, Bopp C, Dewitt W, Dabney P,
the general population. Of 1,432               Mokhtar M, Angulo FJ. Emergence of mul-
patients infected with pansusceptible
strains, 43 patients died (relative mor-
                                               tidrug-resistant Salmonella enterica
                                               serotype Typhimurium DT104 infections in           Serogroup A
tality rate 2.64; 95% CI 1.88 to 3.70).
                                               the United States. N Engl J Med
In other words, the mortality rate in       3. Mølbak K, Baggesen DL, Aarestrup FM,               meningitidis
patients infected with strains resistant
to ACSSuT (Nx susceptible) was 1.6
                                               Ebbesen JM, Engberg J, Frydendahl K, et
                                               al. An outbreak of multidrug-resistant,         Outside Meningitis
times higher than in patients with pan-
                                               quinolone-resistant Salmonella enterica
                                               serotype Typhimurium DT 104. N Engl J
                                                                                               Belt in Southwest
susceptible strains (p value for homo-         Med 1999;341:1420–5.                                Cameroon
geneity 0.22). These estimates were         4. Baggesen DL, Sandvang D, Aarestrup FM.
not adjusted for coexisting conditions         Characterization of Salmonella enterica            To the Editor: Epidemic meningi-
                                               serovar Typhimurium DT104 isolated from        tis associated with serogroup A
as were the estimates in the paper (6).        Denmark and comparison with isolates
    We agree with Dahl that particular         from Europe and the United States. J Clin      Neisseria meningitidis is a devastat-
problems are associated with                   Microbiol 2000;38:1581–6.                      ing disease in the absence of vaccina-
quinolone resistance in zoonotic sal-       5. Walker RA, Lawson AJ, Lindsay EA, Ward         tion (1). Without treatment, the case-
                                               LR, Wright PA, Bolton FJ, et al. Decreased     fatality rate is high, approaching
monellae and that fluoroquinolones             susceptibility to ciprofloxacin in outbreak-
may have reduced efficacy to treat             associated multiresistant Salmonella           100%. In Africa, such epidemics
patients infected with Salmonella              Typhimurium         DT104.      Vet     Rec    occur regularly (1) within a well-lim-
strains that are nalidixic acid                2000;147:395–6.                                ited geographic zone, the so-called

                                  Emerging Infectious Diseases • Vol. 9, No. 10, October 2003                                           1351

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