Late Antibiotic Resistance example essay topic

ANTIMICROBIAL RESISTANCE AND JUDICIOUS USE OF ANTIBIOTICS Antibiotics Antibiotics are chemical substances, many of them derived from microorganisms that suppress the growth of other organisms and sometimes kill them. In clinical practice, the antibiotics are used to treat bacteriologically proven infections and also in the prophylaxis of certain diseases. They are sometimes used in the blind or empiric therapy of presumed infection. A different principle governs the selection of antibiotics for each of the above situations.

An antibiotic appropriate for one situation may be absolutely out of context in another situation. The problem is magnified by the availability of increasing numbers of antibiotics and the emergence of resistant strains. The antimicrobial sensitivity varies from country to country, from town to town, hospital to hospital and even in the same hospital, from ward to ward! Thus the choice of an antibiotic need sound clinical judgment, a detailed pharmacological knowledge of the chemical and knowledge of the sensitivity pattern. A close interaction between the clinician and the microbiologist is required to avoid wasteful use of antibiotics. Inappropriate use of antibiotics can cause serious side effects some of which may lead to a fatality or contribute to it.

Of late antibiotic resistance is increasing everywhere and, in some areas, is reaching crisis proportions. Some literature already talks about "Post antibiotic era". The problems of resistance are being addressed today through infection control practices to control outbreaks of resistance, the stress on judicious use of existing antimicrobials and the continuing search for new effective agents. It is important for all of us to understand the inside story of antimicrobial resistance so that we can tackle the problem of resistance scientifically. We doctors, however, need not blame ourselves totally for the state of affairs today. For, the causes of resistance are not only within the realms of the doctor's rounds alone.

Many other factors also contribute. How is antimicrobial resistance quantified? a) Gathering susceptibility data from laboratories. This is however a rough guide as better method is doing a MIC (Minimum inhibitory assay). Even then, the findings may be laced with some bias. For day to day working, however, this is the best method. The information obtained in the laboratory has no meaning unless it is disseminated to the users. b) Gathering more details regarding types of organisms, type of specimens, in-patient / out patients?

What factors affect emergence of antimicrobial resistance? a) Changes in human demographics / behaviour i. Increasing elderly population ii. Increasing use of day-care facilities b) Changes in technology and industry i. Improved technology prolongs lives and with it hospital stay of patients with serious illnesses ii. Use of antibiotics in industry and agri-business c) Economic development i.

Population growth-increasing population density d) Frequent International travel e) Microbial adaptation to change i. Increasing use of broad spectrum antibiotics-increased mutation pressure f) Breakdown of public health measures i. Infection control and Surveillance programmes have to compete with other priority areas for "funding" What are the main target sites for antibacterial action? There are four main target sites: A Cell wall synthesis of the organism I Beta lactams: a. Penicillins b.

Cephalosporins (Cephalexin, cefachlor, cefuroxime, cefamandole, cefotaxime, ceftazidime, cefepime, cefipirone c. Carbapenems (imipenem) d. Cefamycins (cefoxitin) e. Monobactam (aztreonam) B Protein synthesis in the organism I Aminoglycosides (Gentamicin, Netilmicin, Amikacin, Neomycin, Tobramycin, Kanamycin) II Tetracyclines (Tetracycline, Minocycline, Doxycycline) Chloramphenicol IV Lincosamides (Clindamycin, lincomycin) V Macrolides (Erythromycin, Roxithromycin, Clarithromycin, Azthriomycin) VI Fusidic acid C Nucleic acid synthesis I Inhibition of synthesis of precursors - Sulphonamide's, TMP II Inhibition of DNA replication - Quinolones (Nalidixic acid, Norfloxacin, Ofloxacin, Ciprofloxacin) Inhibition of RNA polymerize - Rifampicin D Cell membrane function I Polymyxin II Colistin Amphotericin-B IV Nystatin Resistance can be passed through GENES. How are these genes passed on? A via Chromosomes.

Stable. Allow vertical transmission of resistance only. Not transferable as not spread "laterally". Cause of INTRINSIC RESISTANCE B via Plasmids. Unstable in absence of antibiotics. Transferable among bacteria.

Cause acquired resistance via transposon's ("jumping genes") Types of Resistance Natural resistance: A specific characteristic of a bacterial species, defines the wild phenotype e.g. wild type of Proteus mirabilis are resistant to Tetracyclines, Nitrofurantoin and Colistin. Wild strains of Klebsiella are resistant to Ampicillin Acquired resistance: Specific resistance; characteristic of certain species; arises due to genetic modifications that arise under antibiotic pressure (e.g. S aureus resistant to beta lactams as a result of modifications in the PBP, MRSA or Methicillin Resistant S aureus, VRE or Vancomycin Resistant S aureus) Cross-resistance: When a single resistance mechanism affects several antibiotics within the same family (e.g. Gentamicin resistant S aureus are resistant to all other aminoglycosides). Associated resistance: Occurs when a single resistance mechanism affects antibiotics of different families (e.g. enterobacteriaceae resistant to betalactams and aminoglycosides due to presence of ESBL (Extended Spectrum beta lactamase) and AAC 6' (an aminoglycoside modifying enzyme) What is ESBL or Extended Spectrum Beta Lactamases? ESBL are enzymes that the organism cleverly manufactures that make it resistant to 2nd and 3rd generation of cephalosporins, penicillins and aztreonam. Other antibiotics such as Imipenem and b- lactam inhibitors (e.g. sulbactam, clavulanic acid and tazobactam) remain sensitive. ESBL arise from mutations in the existing plasmid mediated beta lactamases that ultimately cause alteration of configuration of the enzyme.

ESBL are found on large plasmids and have been most commonly detected in Klebsiella, E coli, Acinetobacter, Proteus mirabilis, Serra tia, Morgan ella, Enterobacter species and also in Salmonella. If ESBL is demonstrable, all Penicillins and Cephalosporins should be reported as resistant. When should we suspect an ESBL producing strain? a) Multi resistant Klebsiella and E coli b) Resistance to Ceftazidime / Cefpodoxime/ Cefotaxime / Ceftriaxone/ Aztreonam c) Maintains sensitivity to Cefoxitin d) If MIC is done-demonstration of intermediate or high in the range for sensitivity. What are the main mechanisms of resistance? There are basically three main mechanisms: a) Altered target (e.g. PBP for betalactams, Ribosomes for macrolides, and ADN gyrose for quinolones) b) Altered uptake (e.g. impermeability, Efflux phenomenon, selective permeability via "poring") c) Drug inactivation (e.g. Beta lactamases destroy beta lactams, Aminoglycoside modifying enzymes modify aminoglycosides, Chloramphenicol acetyl transferases destroy chloramphenicol) Situations where antibiotics are often used inappropriately a) Tonsillopahryngitis (usually viral) b) Gastroenteritis (usually self-limiting) c) Minor Wounds with infection (physical cleaning is more important than early use of high level antibiotics) d) Surgical prophylaxis continued beyond 24 hours in a clean case e) Blind "broad spectrum" antibiotic usage in persistent fever or leucocytosis without consideration to the cause. Allows selection of resistant strain under antibiotic pressure. f) Where culture of an organism actually reflects contamination only but not infection g) In presence of a foreign body or in case of a sizeable big abscess that clearly need removal of foreign body / drainage of abscess and not "pumping" of antibiotics Minimum empiric use of antibiotics The empiric use of antibiotics is irrational and dangerous as it may mask diagnosis, results in emergence of resistant organisms and may contribute to life threatening complications.

In the absence of a clear-cut infection, empiric antibiotics may be used when: a) There is an overt evidence of septicaemia / CNS infection b) When diagnosis is apparent c) When patient is immunocompromised The empirical therapy should start after submitting the specimens for isolation of the organism. The therapy should be changed to definitive therapy once the particular organism is grown and the antibiotic sensitivity pattern is known. Prophylaxis of bacterial infections Antibacterial agents are occasionally indicated for use in patients who have no evidence of infection but who have been or are expected to be exposed to bacterial pathogens under circumstances that constitute a major risk of infection. The basic needs of antimicrobial prophylaxis are as follows: . The risk or potential severity of infection should be greater than the risk of side effects from the antibacterial agent. The antibacterial agent should be given for the shortest period necessary to prevent target infections.

The antibacterial agent should be given before the expected period of risk (e.g. Surgical prophylaxis) What is antibiotic policy in a hospital? Antibiotic policy or correct use of antibiotics is formulated based on prevalent organisms. The policy for use of antimicrobials in a hospital needs to be reviewed from time to time. The aim of the policy is to prevent emergence of drug resistant organisms and to ensure cost effective utilisation of drugs. General and specific advantages of an antibiotic policy: Knowledge.

Promotes awareness of benefits, risks and cost of prescribing. Reduces impact of aggressive marketing by pharmaceutical industry. Encourages rational choice of drugs on scientific basis. Provides education about local epidemiology of pathogens and their ABST pattern Attitudes and behaviour.

Acceptance by clinicians of importance of setting standards of care & prescription. Acceptance of peer review and audit of prescribing. Recognition of importance of specific expertise required for full evaluation of antimicrobial chemotherapy. Reduction of medical practice variation. Improved liaison among clinicians, microbiologists, pharmacists and infection control team Outcome. Improved efficacy of prescribing.

Improved clinical outcome. Reduction of medico legal liability. Limitation of emergence of drug resistant strains The Infection Control Team in a hospital- Preparation to control emergence of antibiotic resistance in a hospital setting The chairman of the Hospital Infection control Committee will usually be the CO / Commandant. The Deputy Commandant, senior most Medical Specialist, the Pathologist, Anaesthetist (or OI / C OT, CSSD and ICU), OI / C Medical Stores, Principal Matron, Deputy Principal Matron, Registrar (or an Officer trained in Hospital Administration), and Officer in charge of Hospital Waste Disposal System are members of this committee.

The senior most Medical Specialist will be the Officer in charge of Antibiotic Policy in a hospital. In all, it is team work that contributes to the success of an Infection Control Team. 2. The responsibility of the committee include checking on preventive measures against spread of infections, ensuring that correct measures are adopted in maintaining strict asepsis during hospital procedures and to ensure that infective waste is disposed as per laid down policy. 3.

The CSSD and OT provide sterile dressings, needles, syringes, diagnostic sets and other sterile items. The staff will constantly strive to achieve the highest standards of sterility of the material provided to wards and departments. 4. The senior anesthesiologist keeps a check on the functioning of CSSD, OT, ICU, and CCU and ensures that autoclave efficiency is checked periodically and recorded in a register. Periodic bacteriological cultures need to be sent from the OT, ICU and CCU to keep a check on the existing sterility conditions. All instruments used for various procedures and stock solutions should also be submitted for periodic sterility checks.

5. All wards and departments should ensure proper disposal of various categories of waste (both infectious and non-infectious) in their own areas, in consultation with the Officer in charge of Hospital Waste Disposal System and as per laid down SOP on the subject. 6. The following swabs should be sent every fortnight from OT, ICU, Burns ward, Labour room and NICU: Floor swabs, Wall swabs, Trolley / Table swabs, Swab from the inside of baby incubator, air culture on settle plates from OT. A record of results should be maintained in a separate register by the concerned ward. 7.

The hospital laboratory should provide antibiotic sensitivity tests against bacterial isolates from infected cases. The trends of antibiotic sensitivity should be conveyed at every monthly clinical meeting and a quarterly appraisal given to the Infection Control Committee. Necessary steps are taken depending on the sensitivity patterns and opinion of the committee members. Epidemic strains (MRSA and other resistant staphylococci, any new epidemic strain isolated, epidemic Pseudomonas species) and their antibiotic sensitivity patterns should be conveyed by the pathologist on PRIORITY to the concerned specialist and also to the Officer in charge of the Hospital Infection Control Team.

8. The Hospital Infection Control Committee may meet quarterly to discuss the previous quarter's data. Antibiotic "holidays " may have to be given in consultation with the Officer in charge of Medical Stores. In addition to the quarterly meetings the laboratory can provide the antibiotic sensitivity patterns in any month and point to any impending resistance emerging due to over usage of an antibiotic. Any spread of resistant strains can also be brought out. 9.

The antibiotic policy (both at issue and user points) will be reviewed from time to time by the Infection Control Team. The purpose of the policy measures should be the following: a) To prescribe adequate quantity of the most effective, most economical an easy to administer drugs in the given situation. b) To monitor the infection pattern of in-patients ward and department wise. c) To reduce the possible development of resistant strains in the hospital by selective and judicious use of antibiotics. Conclusion The large array of antibiotics available is indeed bewildering and confusing. Numerous "surveys" have reported that at least 50% of antibiotic usage were "unnecessary" and in some way "inappropriate". Aside from the cost involved there are the cost, mental agony of adverse effects, drug interactions and eventual cost of treating mutant organisms.

Many a time such mutants can claim a precious life! The following suggestion a are offered by an esteemed clinical author: - a) Objective evidence regarding the merits of newer drugs may be read from medical literature before starting them on the basis of what the Company manufacturing it says. b) Clinicians should resist the temptation of using new drugs unless the merits are clear. A newer drug with broader spectrum and longer half life does not necessarily mean greater clinical efficacy c) Clinicians should be familiar with local bacterial susceptibility patterns and should refrain from changing to a new drug if the organism is obviously sensitive to the older drug d) For empirical use a narrow spectrum is advisable e) Cultures should always be sent before starting antibacterial therapy: results if positive may be vital for management of the case! f) If antibiotic sensitivity is available, it is wiser to switch to a more specific agent rather than carry on with a broad spectrum agent: this will avoid undue selection pressure on the organism to mutate. If these guidelines are followed, the care of the patients will not be undermined, many unnecessary complications averted and the useful life of valuable drugs will be extended.