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Infectious Diseases Pharmacology
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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Unpublished data from our institution and elsewhere3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 drugs has not kept up with the increase in bacterial 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[CrossRef][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[CrossRef][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[CrossRef][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[CrossRef][ISI][Medline]. |
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