CURTAILING ANTIMICROBIAL RESISTANCE
Dr. S. SRINIVASAN *
JIPMER, Pondicherry *
Bacteria have been very ingenious in circumventing each new therapy, so that only long-term prevention is really effective". - Dominique L. Monnet (the Statens Serum Institute in Copenhagen)

Every pediatrician in India and the other neighbouring developing countries have experienced the difficulties in treating children with multidrug resistant salmonella typhi infections and shigella dysenteric episodes. The other important area in which she / he encounters this problem of antimicrobial resistance is malaria, more importantly with regard to treatment of cerebral malaria. She / he has experienced increasing difficulty in treating urinary tract infections and recently acute bacterial pneumonias. The intensivists in intensive care units face the problem of nosocomial infections due to multidrug resistant gram negative pathogens and staphylococci. The unprecedented level of concern about increasing drug resistance involving a wide variety of human pathogens, both in the community and in the hospitals, reflects the growing frustration with the intractability of this multifaceted problem. Antimicrobial resistance among bacterial pathogens has become a serious health threat, and the incidence is rising at an alarming rate. The National Foundation for Infectious Diseases has ranked antimicrobial resistance and emerging infections as the first among the top 10 problems in infectious diseases.

Antimicrobial resistance has definitely resulted in an increased rate of in-hospital mortality, increased morbidity, and a longer length of hospital stay and higher healthcare costs. In US hospitals, annual estimated expenses associated with antibiotic resistance range from $100 million to $30 billion.

Lessons Learned About Antibiotic Resistance
Giving enough antibiotic and time, resistance will appear. For example, the penicillin-resistant Streptococcus pneumoniae took 25 years to become a clinical problem; fluoroquinolone-resistant Enterobacteriaceae took 10 years to emerge clinically.

Resistance is progressive, moving from low to intermediate to high levels.

Organisms that are resistant to one antibiotic will likely become resistant to others. For example, tetracycline resistance in Neisseria gonorrhoeae first appeared among strains with existing resistance to penicillin.

Once selected, drug resistance will not disappear, although it may decline slowly. This gradual decrease in resistance is associated with poorly reversible genetic and environmental factors. No counterselective steps against resistant bacteria now exist.

When antibiotics are used by any patient, this use affects other people by changing the microbiology in both the immediate and the extended environment.

Definition of terms (Novak, 1999)
Tolerance is the ability of bacteria to survive in the presence of antibiotics, but not to continue cell division.

Resistance, on the other hand, is when bacteria can both survive and duplicate when antibiotics are present.

e.g., Documented cases of Vancomycin tolerant strains Streptococcus pneumoniae causes a great concern, because tolerance is often a direct precursor to resistance, this observation is of serious concern. Resistance to vancomycin might leave no alternative for patients. (Novak, 1999).

Postulated mechanisms for the appearance and spread of antimicrobial resistance in hospitals:
  1. Introduction of a resistant organism to a previously susceptible population
  2. Acquisition of resistance by a susceptible strain (via spontaneous mutation or genetic transfer
  3. Expression of regulated resistance already present in the population
  4. Selection of a resistant subpopulation
  5. Dissemination or spread of resistant organisms

Reasons for the emergence and spread of resistance in ICUs:
A unique facilitating setting
  1. Close quarters and high frequency of staff-to-patient contact can increase patient-to-patient contact
  2. Cross-transmission of pathogens due to lack of hand washing (and hand-washing rates decline with increased workload)
  3. Heavy selection pressure by broad-spectrum antibiotic use; and
  4. Environmental contamination providing further opportunity for cross-transmission of pathogens via contaminated equipment and hands of healthcare workers

Prevention of infections caused by Antimicrobial - Resistant Pathogens - A Comprehensive Approach.
  1. Prevention of infections through the use of vaccines and prophylaxis
  2. Proper hand-washing
  3. Use of sterile linen, materials and equipments
  4. Minimal use of invasive devices, catheters, drainage tubes, etc
  5. Implementation and compliance with current guideline recommendations for the prevention of infections
  6. Avoidance of prolonged hospital stay and
  7. Judicious use of antimicrobials:

    - Minimal use of Antibiotics with high resistance potential (e.g., Ampicillin, Carbenicillin, Ciprofloxacin, Imipenem, Ceftazidime, Tetracyclines, Gentamicin)

    - Preferential use of Antibiotics with little or no resistance potential (e.g., Third Generation Cephalosporins (except ceftazidime), Cefepime, Piperacillin, Quinolones (except Ciprofloxacin), Amikacin, Meropenam, Ceftazidime, Doxycycline, Minocycline)

10 strategic goals to contain antimicrobial resistance
The goals that target antibiotic use:
  1. Optimize prophylactic antimicrobial use prior to surgical procedures
  2. Optimize choice and duration of empiric antimicrobial use
  3. Improve antimicrobial prescribing practices through educational and administrative means

  4. Establish a system that monitors and provides feedback regarding the occurrence of resistance, and
  5. Define and implement guidelines for antimicrobial use

The goals that target infection control measures:

  1. Develop a means of recognizing significant changes in resistance and reporting these shifts to staff with a need to know
  2. Develop a system for rapid detection and reporting of resistant organisms in individual patients so that their caregivers and treating staff are well informed

  3. Increase compliance with basic infection - control techniques, including hand hygiene and barrier methods
  4. Incorporate detection, prevention, and control of antimicrobial resistance into the strategic goals of the institution, and
  5. Develop a plan for appropriately treating, transferring, discharging, and readmitting patients known to be colonized with resistant organisms

Specific measures to manage antimicrobial by modifying patterns of antibiotic use:

  1. Restriction of certain classes of antibiotics
  2. Rotation or cycling classes of antibiotics periodically

  3. Open formularies
  4. Physician education - critical component of any successful program to manage antibiotic use, whether by a restricted formulary, use of antibiotic order forms, requirement of
  5. Approval by an infectious disease specialist
  6. Prospective educational intervention programs
  7. Computerized physician order entry with decision support and real-time feedback to physicians has been shown to be an efficient means of antibiotic management

Advantages and Benefits of Antibiotic Resistance Control Strategies:
  1. Reduction in the rate of infections
  2. Improved patient outcomes
  3. Reduction in the prevalence of antimicrobial-resistant pathogens
  4. Decrease healthcare-related costs
Conclusion
Preventing antibiotic-resistant requires a multifaceted approach.
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