FIGHTING BACK
Bacterial resistance to antibiotics is becoming a worrisome problem in the battle against infections, warns the latest Antimicrobial Resistance Surveillance report
Antibiotics are substances produced by microorganisms that kill or inhibit other microorganisms. In 1929 Sir Alexander Fleming's discovery of penicillin--the first antibiotic--by inhibiting staphylococci on an agar plate contaminated by a Penicillium mold heralded modern man's great leap into chemotherapy against bacterial infections. The importance of the discovery was not lost in World War II, when penicillin became generally available for treatment of war-related wound infections.
A great many related discoveries followed suit. The late 1940s and early 1950s saw the discovery and introduction of streptomycin, chloramphenicol, and tetracycline, and the age of antibiotic chemotherapy came into full being. They were effective against a full array of gram-positive and gram-negative bacterial pathogens, intracellular parasites, and even the tubercle bacillus.
Bacterial resistance
The therapeutic success of the antimicrobials, however, would itself lead to an ominous phenomenon called resistance. Bacterial resistance makes an infection much harder to treat. Further management may actually require higher doses or stronger drugs and, in extreme cases, can be fatal.
Resistance to penicillin by some strains of staphylococci was recognized almost immediately after introduction of the drug (today, it occurs in as many as 80 percent of all strains of Staphylococcus aureus). In 1953, during a Shigella outbreak in Japan, a strain of the dysentery bacillus was isolated and found resistant to chloramphenicol, tetracycline, streptomycin, and the sulfanilamides. Chemotherapeutic success has spawned bacterial resistance.
Overprescription, drug misuse
The United States Centers for Disease Control and Prevention (CDC) now maintains that widespread overprescription and misuse of antibiotics are the main causes of bacterial resistance, promoting new strains of harmful bacteria that resist traditional treatments.
Up to half of the roughly 100 million prescriptions for antibiotics written each year are unnecessary, a communiqué warns.
If a prescribed course of medication is not completed, only those bacteria most susceptible to antibiotics may be destroyed. The remaining, harder-to-eliminate bacteria are left to reproduce and cause illnesses that are more serious. Likewise, if bacteria come into contact with--but are not killed by--an antibiotic, they may adapt their cell structure to render themselves "immune" to future medication.
Common illnesses caused by viruses may also be typically prescribed antibiotics. Antibiotics are not effective against viruses, only bacteria, and are therefore useless in fighting viral infections.
Bacterial evolution
Miroorganisms might exhibit resistance to drugs by many different mechanisms. The following are fairly well supported by evidence.
Inherent (natural) resistance. Bacteria may be inherently resistant to an antibiotic.
Acquired resistance. Bacteria can develop resistance to antibiotics, for example, populations previously sensitive to antibiotics become resistant. This type of resistance results from changes in the bacterial genome. Genetic processes drive it, such as mutation and selection and the exchange of genes between strains and species.
Vertical evolution. Through natural selection, a spontaneous mutation in the bacterial chromosome imparts resistance to a member of the bacterial population.
Horizontal evolution entails the acquisition of genes for resistance from another organism.
The combined effects of fast growth rates, high concentrations of cells, genetic processes of mutation and selection, and the ability to exchange genes, account for the extraordinary rates of adaptation and evolution that can be observed in the bacteria. For these reasons bacterial adaptation (resistance) to the antibiotic environment may take place very rapidly. Surveillance resistance data thus provide the necessary antimicrobial resistance patterns to adequately plot potential susceptibility and suggest treatment recommendations.
Philippine antimicrobial surveillance
Since 1988, the Department of Health Committee on Antimicrobial Resistance Surveillance annually commissions Philippine antimicrobial surveillance and updates treatment recommendations based on data gathered from 17 sentinel sites all over the country which include the following:
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Research Institute for Tropical Medicine (RITM)
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San Lazaro Hospital
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Philippine General Hospital
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Nicanor Reyes Memorial Medical Center (FEU Hospital)
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National Kidney Institute
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Lung Center of the Philippines
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Rizal Medical Center
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University of Santo Tomas Hospital
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Celestino Gallares Memorial Medical Center, Tagbilaran City
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Zamboanga Medical Center
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Corazon Locsin Memorial Medical Center, Bacolod City
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Eastern Visayas Regional Medical Center, Tacloban City
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Vicente Sotto Memorial Medical Center, Cebu City
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Davao Medical Center
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Cotabato Regional Hospital and Medical Center
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Baguio General Hospital
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Bicol Regional Training and Teaching Hospital, Legazpi City
Rational drug use
"A lot of practices contribute to resistance," notes Dr. Celia Carlos, committee chair and consultant in pediatrics and infectious diseases at the RITM and St. Luke's Medical Center. "So each of the stakeholders must do their share. For
example, government is trying to do its part. The Essential Drugs List [is used] to promote rational or appropriate antibiotic use. But what is rational drug use? The WHO (World Health Organization) defines it as the choice of the most cost-effective antibiotic, the maximum or best therapeutic effect with minimal side effects and tendency to develop resistance."
2004 updates
In the latest update on the Philippine Antimicrobial Resistance Surveillance (2004), bacterial resistance patterns have changed over time, especially among the respiratory pathogens Haemophilus influenzae, Streptococcus pneumoniae, and the gram-negative organisms such as E. coli.
Resistance rates of H. influenzae have peaked sharply for co-trimoxazole (40.9 percent v. 18 percent previous), and no major improvements were seen for chloramphenicol- and ampicillin-resistant isolates (10 to 13 percent). The figures for S. pneumonia were not reassuring either. Resistance to co-trimoxazole increased to 13.4 percent from nine percent in 2003 but with some improvement for chloramphenicol (down 3.8 percent from nine percent). Resistance to penicillin remained at three to 3.8 percent.
Many of the Enterobacteriaceae showed high resistance rates to several antibiotics. Seventy-seven percent and 68 percent of Escherichia coli isolates were resistant to ampicillin and co-trimoxazole, almost the same as in 2002 and 2003. It remained relatively susceptible to third- and fourth-generation cephalosporins but registered high resistance rates to second-generation cephalosporins (cefuroxime at 20 percent). Against ceftriaxone, a low resistance rate (six percent) was generally observed.
The presence of extended-spectrum beta-lactamase (ESBL) production had been confirmed and mapped for bacterial isolates of E. coli and Klebsiella from nine sentinel sites. Alternative antimicrobials for therapy of ESBL-producing organisms may include carbapenems, beta-lactam/beta-lactamase inhibitor combinations, aminoglycosides, and fluoroquinolones.
Pseudomonas aeruginosa had high resistance rates to gentamycin (30.3 percent), ciprofloxacin (29.7 percent), tobramycin (26.2 percent), and netilmicin (25.5 percent). However, recommendations for empiric antibiotic therapy may still include amikacin (20.8 percent), ceftazidime (17.3 percent), cefipime (19.3 percent), and imipenem (20.6).
Almost 83 percent of Staphylococcus aureus isolates remained sensitive to oxacillin for all institutions, likewise for ciprofloxacin (6.8 percent), co-trimoxazole (4.8 percent), erythromycin (9.2 percent), and vancomycin (0.1 percent). Benzylpenicillin resistance was maximum at 94 percent. Methicillin-resistant S. aureus remained largely susceptible to vancomycin or teicoplanin.
By and large, the 2004 update maintains that "bacterial resistance to antibiotics has become a major factor to contend with in the treatment of infectious diseases in the Philippines." As data largely vary from country to country, it recommends providing for "locally generated culture and susceptibility data as basis for determining appropriate antimicrobial choices." Programs to sustain disease surveillance and reporting need to be emphasized by governments as a backbone in communicable-disease control.
But the effort does not rest with government alone. Frequent and improper use (prescribing) of antibiotics by physicians, self-medication by patients, inappropriate promotional activities by drug companies, and laxity by pharmacists in dispensing drugs contribute to increasing resistance rates.
"There is a need to educate [medical] practitioners, [the] pharmaceutical industry, pharmacists, and especially patients themselves," stresses Carlos.
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