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    Add as FriendAnti-biotics drug- Therapeutic Considerations

    by: Gaurav

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    1 : Antibiotic Drugs – Therapeutic Considerations
    2 : Definition Anti-infective agents treat infection by suppressing or destroying the causative micro-organisms – bacteria, mycobacteria , fungi, protozoa or viruses Antibiotics – derived from natural substances Antimicrobials – produced from synthetic substances Terms interchangeable
    3 : Antimicrobial therapy is prescribed in three clinical circumstances To treat bacteriologically proven infection. Empirical use on the basis of clinical assessment of presumed infection. Chemoprophylaxis against infection
    4 : Indications Confirm presence of infection Detailed, complete history Physical examination Signs and symptoms of infection Predisposing factors Start antibiotics only when – significant infection diagnosed / strongly suspected Established indication for prophylactic therapy exists
    5 : Common clinical and laboratory findings associated with infection Clinical – Localized Inflammation at site of infection- RCDT Sputum production and cough Diarrhoea Vaginal and urethral discharges Skin lesions
    6 : Contd.. Systemic Fever, chills, rigor Increased heart rate, Increased respiratory rate Malaise Mental status changes, Hypotension Laboratory Increased WBCs, Immature neutrophil band, shift to left Positive cultures/ gram stains Increased ESR Positive antigen or antibody titres
    7 : Establish severity of infection Hemodynamic changes Cellular changes Respiratory changes Hematologic changes Neurologic changes
    8 : Problems in the diagnosis of infection Confounding variables Drug effects Fever
    9 : Determine the site of infection Respiratory UTI Skin Gastroenteritis Meningitis Intra abdominal
    10 : Determine likely pathogens Viral /bacterial/fungal/protozoal Gram negative/ positive Aerobes/ anaerobes
    11 : Susceptibility Tests Different strains of same pathogenic species have widely varying susceptibility to a particular anti-infective agent These tests determine microbial susceptibility to a given drug Used to predict whether the drug will combat the infection effectively.
    12 : Various methods of antibiotic susceptibility testing Quantitative Methods Qualitative Methods Automated Susceptibility Tests Newer Non-Automated Susceptibility Tests Molecular Techniques
    13 : The lowest drug concentration that prevents microbial growth after 18 – 24 hrs of incubation – minimum inhibitory concentration (MIC) The lowest drug concentration that reduces bacterial density by 99.9% - minimum bacterial concentration (MBC)
    14 : Quantitative Methods In these tests, the minimum amount of antibiotic that inhibits the visible growth of an isolate or minimum inhibitory concentration (MIC) is determined. Bacterial isolate is subjected to various dilutions of antibiotics. The highest dilution of antibiotic that has inhibited the growth of bacteria is considered as MIC. These tests can be performed on broth or agar. 1. Broth dilution methods a. Macrobroth dilution MIC tests b. Microbroth dilution MIC tests 2. Agar dilution methods
    15 : a.Macrobroth dilution tests A serial two-fold dilution of antibiotic are made in test tubes from 0 to maximum concentration that is achieved in vivo without toxic effect on patient. 1ml of bacterial suspension is added to rows of antibiotic solution and incubated at 37oC overnight. The lowest concentration of antibiotic that completely inhibits visual growth of bacteria (no turbidity) is recorded as MIC.
    16 : b.Microbroth dilution tests: A polystyrene tray containing 80 wells is filled with small volumes of serial two-fold dilutions of different antibiotics. The bacterial inoculum is then inoculated into the wells and incubated at 37oC overnight. MIC is determined as in macrobroth dilution test
    17 :
    18 : 2.Agar dilution method A serial two-fold dilution of the antibiotic is prepared in Mueller-Hinton agar. Using calibrated loops a volume of 0.001-0.002 ml is inoculated on the surface of agar and incubated at 37oC overnight. The lowest concentration of antibiotic that inhibits visible growth on surface of agar is taken as MIC
    19 : Qualitative Methods These tests categorize a bacterial isolate as sensitive, intermediate or resistant to a particular antibiotic Disk diffusion test: In this method the standardized bacterial isolate is spread on an agar plate and then paper disc containing specific concentration of antibiotics are placed and incubated at 37oC overnight
    20 : If the isolate is susceptible to the antibiotic it does not grow around the disk thus forming a zone of inhibition. Strains resistant to an antibiotic grow up to the margin of disk. The diameter of zone of inhibition must be measured and result read from the Kirby Bauer chart as sensitive, intermediate or resistant
    21 : Figure : Antibiotic susceptibility tests (Disk diffusion method)
    22 : Automated Susceptibility Methods Determination of bacterial growth in wells containing antimicrobial agent are performed in short period of time using computer-assisted instruments. Various techniques include: Turbidimetric detection: VITEK (report ready in 4-15 hours) Flourimetric detection: AutoSCAN Walkaway (report ready in 3.5-7 hours) Video Image processing: ALADIN (report ready in 18-24 hours)
    23 : Newer Non Automated Susceptibility Tests: Alamar system, E-test and Spiral gradient endpoint system Molecular Techniques: Detection of gene coding for resistance to one or several drugs by techniques such as PCR and DNA hybridization.
    24 : Intrinsic resistance means that the species was resistant to an antibiotic even before its introduction. Acquired resistance means that the species was originally susceptible to an antibiotic, but later became resistant. Bacteria can acquire antibiotic resistance either by mutation or through exchange of genetic material among same or closely related species. The sudden acquisition of resistance to antibiotics poses difficulties in treating infections. Bacteria demonstrate two kinds of resistance to antibiotics
    25 : Resistance to several different antibiotics at the same time is even more significant problem. It is because of the acquired resistance that bacterial isolates must be subjected to antibiotic susceptibility testing. Bacteria showing reduced susceptibility or resistance to an antibiotic implies that it should not be used on the patient
    26 : Culture and identification Bacteria can be identified by- Gram stain Growth characteristics (type of media, aerobic/anaerobic) Colonial morphology Biochemical profile
    27 : Determination of isolate pathogenicity Colonization Contamination Infection
    28 : Antimicrobial toxicities Adverse effects and toxicities Concomitant disease states
    29 : Route of administration and antimicrobial dosing Route Severity of infection Bioavailability Patient specific factors Dosing Site of infection Anatomic and physiologic barriers Route of elimination patient age Fever
    30 : Antimicrobial costs of therapy Usage frequency Single/ multiple doses Special administration procedures Monitoring cost (lab tests) Renal excreted drug (creatinine clearance)
    31 : Choice of agent Patient factors Immunologic status Presence of a foreign body Age Underlying disease – Kidney/ liver disease CNS disorder Neuromuscular disorders History of drug allergy/ ADR Pregnancy and lactation Genetic triats – G6PD defficiency Fast acetylators
    32 : Empiric Therapy In serious/ life threatening disease – AI therapy must begin before the infecting organism has been identified The choice of drug is based on clinical experience A broad spectrum antibiotic is the most appropriate choice Culture specimens must be obtained
    33 : Multiple antibiotic therapy Combination therapy – experience and effective – effective than single therapy Can increase the risk of toxic drug effects, drug antagonism and t’peutic ineffectiveness Indications – Need for increased antibiotic effectiveness- synergistic Treatment of an infection caused by multiple pathogens Prevention of proliferation of drug resistant organisms
    34 : Duration of anti – infective Therapy To achieve therapeutic goal – sufficient duration Acute uncomplicated infection – till afebrile and asymptomatic for atleast 72 hrs Chronic infection – require longer duration 4-6 weeks- with follow up analysis, culture tests for therapeutic effectiveness
    35 : Monitoring therapeutic effectiveness Fever curve Defervescence indicated favorable response White blood cell count Neutrophilia, immature neutrophil bands Radiographic findings Small effusions, cavities Pain and inflammation Evidence of swelling, erythema, tenderness Erythrocytic sedimentation rates elevations Serum complement concentrations Reduction in C3 component
    36 : Immature Neutrophil band
    37 : ESR ESR is increased in all conditions where there is tissue breakdown or where there is entry of foreign proteins in the blood, except for localized mild infections The determination is useful to check the progress of the disease. If the patient is improving, ESR tends to fall If patient condition gets worse the ESR tends to rise The changes of ESR however not diagnostic of any specific disease
    38 : Assessment of therapy (When the expected response is not observed, a review of the following is needed) Is the isolated organism really the causative one? Is another, previously unsuspected disease present? Is there accumulated pus (which needs drainage)? Is there a foreign body (e.g. unaccounted swab in the abdomen following surgery)? Has resistance to the drug or superinfection developed? Is there an iatrogenic complication (e.g. thrombophlebitis or drug fever)?
    39 : Lack of therapeutic effectiveness Misdiagnosis – Organism misidentified Improper drug regimen Wrong Dose, route, frequency, duration Inappropriate choice of antibiotic agent P’cological aspects, spectrum of activity Microbial resistance Excessive use Infection by two or more types of microorganisms
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