[e-drug] Restored sensitivity to older antibacterials?

[Valeria Frighi <valeria.frighi@dtu.ox.ac.uk>]

E-drug: Restored sensitivity to older antibacterials?
---------------------------------------------

Old drugs for new bugs
BMJ 2003;326:235-236 ( 1 February )

[Copied as fair use]

Editorials

Anecdotes suggest that some bacteria have lost their resistance to
older antibiotics

Recent reports have lent support to the potential use of previous
generation antibacterial drugs to treat infections caused by new resistant
bacteria. The Morbidity and Mortality Weekly Report recently
described two isolates from the United States of vancomycin resistant
Staphylococcus aureus with a minimum inhibitory concentration 32
µg/ml, both of which were found to be sensitive in vitro to
co-trimoxazole as well as to other older antimicrobials. 1 2
Co-trimoxazole was successfully used to treat one of these patients.1
Unpublished data from our institution and elsewhere3 show that in the
last 15 years isolates of methicillin resistant S aureus (MRSA) have
progressively, and by now almost universally, become susceptible to
co-trimoxazole.

Preliminary data indicate that this drug can be used as an alternative
to vancomycin to treat infections due to MRSA4 and include a case
report about co-trimoxazole being used successfully to treat a
patient with endocarditis that failed to respond to linezolid.5

Chloramphenicol, a drug introduced 50 years ago and essentially
abandoned in the past three decades, has been reintroduced recently
to treat severe infections caused by vancomycin resistant
enterococci.6 A report from India describes the re-emergence of
susceptibility to chloramphenicol in Salmonella typhi isolates that
are increasingly resistant to quinolones and lactams.7 The authors
suggest reintroducing this drug to treat typhoid fever.

In a recent report from France, Stein and Raoult used colistin, an old
and rarely used antibiotic, to treat bone infections caused by a
strain of Pseudomonas aeruginosa with resistance to all other
antibiotics tested.8 The same drug has been used to treat infections
caused by multiresistant strains of Acinetobacter baumannii.9
Sulbactam, a drug introduced in the early 1980s, is increasingly
being used for the same purpose.10 As an alternative to third
generation cephalosporins and vancomycin, high
doses of penicillin are being proposed to treat pneumococcal infections
caused by strains with intermediate levels of penicillin resistance
(minimum inhibitory concentration 4-8 µg/ml).11

Despite extensive research the pace of development of antibacterial
   resistance. As more and more organisms develop resistance, concern is
growing that we may be approaching the end of the antibiotic era. The
intensive use and excessive abuse of antibiotics have resulted in the
selection of bacteria that are resistant to many and sometimes all
antibiotics. For unclear reasons, these multiresistant organisms
either retain or regain susceptibility to certain antimicrobials.

Measures to counter the threat of rapidly escalating antimicrobial
resistance include surveillance of susceptibility to and consumption
of antibiotics, rational use of antibiotics, better compliance with
measures to control infection, and increasing development and use of
vaccines.

Are we reverting to the pre-antibiotic era or advancing into the
post-antibiotic era? One of the crucial questions is whether the
above mentioned examples will remain anecdotal or whether a real
chance
exists for the strategic use of forgotten drugs on a large enough
scale to affect clinical management.

The recovery of sensitivity to specific antimicrobials by pathogenic
bacteria is a complex issue. Two important factors determine rates of
resistant bacteria in a specific community the "human" factor, which
is the amount of antimicrobials used, and the "biological" factor,
which is the burden that the resistance encoding genes impose on the
fitness of the bacteria.12

The impact of either the discontinuation or the reintroduction of a
specific drug on the rate of resistance will differ for various
microorganisms. In addition to the information obtained from
mathematical models of population dynamics,12 continuous
surveillance of in vitro susceptibility will inform us about the effect
of reintroducing older drugs. In some instances, resistance could
rapidly re-emerge owing to the presence of low rates of resistant
genes in a population that once was predominantly resistant. In the
future, older antimicrobials will be relied on more and more, either
as isolated "no other choice" options or as part of a programmed
policy of antibiotic cycling.

Silvio Pitlik.

Department of Medicine and Infectious Diseases, Rabin Medical Center,
49100 Petah Tiqva, Israel (spitlik@clalit.org.il)

Footnotes

Competing interests: None declared.

   1.
      Centers for Disease Control and Prevention. Staphylococcus aureus
resistant to vancomycinUnited States, 2002.
      Morb Mortal Wkly Rep MMWR 2002; 51: 565-567.
   2.
      Centers for Disease Control and Prevention. Public health dispatch:
vancomycin-resistant Staphylococcus
      aureusPennsylvania, 2002. Morb Mortal Wkly Rep MMWR 2002; 51: 902.
   3.
      Denis O, Deplano A, Nonhoff C, de Ryck R, Rottieres S, Hendricks E,
et al. Molecular epidemiology and antimicrobial
      susceptibility of methicillin-resistant Staphylococcus aureus in
Belgian hospitals: 2001. 42nd ICAAC Abstracts. In: San
      Diego: American Society for Microbiology, 2002:305.
   4.
      Markowitz N, Quinn EL, Saravolatz LD. Trimethoprim-sulfamethoxazole
compared with vancomycin for the treatment of
      Staphylococcus aureus infection. Ann Intern Med 1992; 117:
390-398[ISI][Medline].
   5.
      Ruiz ME, Guerrero IC, Tuazon CU. Endocarditis caused by
methicillin-resistant Staphylococcus aureus: treatment failure
      with linezolid. Clin Infect Dis 2002; 35: 1018-1020[ISI][Medline].
   6.
      Lautenbach E, Schuster MG, Bilker WB, Brennan PJ. The role of
chloramphenicol in the treatment of bloodstream
      infection due to vancomycin-resistant enterococcus. Clin Infect Dis
1998; 27: 1259-1265[ISI][Medline].
   7.
      Sood S, Kapil A, Das B, Jain Y, Kabra SK. Re-emergence of
chloramphenicol-sensitive Salmonella typhi. Lancet 1999;
      353: 1241[ISI][Medline].
   8.
      Stein A, Raoult D. Colistin: an antimicrobial for the 21st century?
Clin Infect Dis 2002; 35: 901-902[ISI][Medline].
   9.
      Jimenez-Mejias ME, Becerril B, Marquez-Rivas FJ, Pichardo C, Cuberos
L, Pachon J. Successful treatment of
      multidrug-resistant Acinetobacter baumannii meningitis with
intravenous colistin sulfomethate sodium. Eur J Clin
      Microbiol Infect Dis 2000; 19: 970-971[ISI][Medline].
   10.
      Cawley MJ, Suh C, Lee S, Ackerman BH. Nontraditional dosing of
ampicillin-sulbactam for multidrug-resistant
      Acinetobacter baumannii meningitis. Pharmacotherapy 2002; 22:
527-532[ISI][Medline].
   11.
      Bryan CS. Treatment of pneumococcal pneumonia: the case for
penicillin G. Am J Med 1999; 107(1A):
      63s-68s[Medline].
   12.
      Levin BR. Minimizing potential resistance: a population dynamics
view. Clin Infect Dis 2001; 33(suppl 3):
      s161-s169[ISI][Medline].

-- 
Dr. Valeria Frighi
Diabetes Trials Unit
Radcliffe Infirmary
Woodstock Road
Oxford OX2 6HE
UK
tel. -44-1865-228422
fax -44-1865-224584
e-mail valeria.frighi@dtu.ox.ac.uk
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