Antibiotics basics for clinicians

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  • 1.Dr. LokeshGargM.B.B.S. M.D.

2. One of the most commonly used group of drugs. A medical doctor has to know the definite clinical pharmacologyof antibiotics, how to select & use them rationally.- Avoid adverse effects on the patient- Avoid emergence of antibiotic resistance- Avoid unnecessary increases in the cost of health care 3. DefinitionAntibiotics are substances that kill or inhibit the growthof micro-organisms. BacteriostaticBactericidal 4. Based on their mechanism ofaction, antibiotics can be dividedinto the following classes: Inhibitors of Cell Wall synthesis Inhibitors of Protein synthesis Inhibitors of Nucleic Acid synthesis 5. This class includes: Penicillin Cephalosporin Carbapenems Monobactams Vancomycin Beta lactamase inhibitorsB lactamantibiotics 6. Category Parenteral Agents Oral AgentsNatural Penicillins Penicillin G Penicillin VAntistaphylococcalpenicillinsNafcillin, oxacillin DicloxacillinAminopenicillins Ampicillin Amoxicillin andAmpicillinAminopenicillin + -lactamase inhibitorAmpicillin-sulbactam Amoxicillin-clavulanateExtended-spectrumpenicillinPiperacillin, ticaricillin CarbenicillinExtended-spectrumpenicillin + -lactamaseinhibitorPiperacillin-tazobactam,ticaricillin-clavulanateTHE PENICILLINS 7. Class Examples Routes ofadministrationFirst generation Cephalexin/cefadroxilCefazolinOrali.v.SecondgenerationCefuroximeCefoxitinOral/ i.v.Third generation CefiximeCeftriaxone/cefotaximCeftazidimeOrali.v.i.v.FourthgenerationCefipime i.v. 8. Adverse Effects Allergic reactions: itch, rash,fever, angioedema, rarelyanaphylactic reaction GI upset and diarrhoea Interstitial nephritis andincreased renal damage incombination withaminoglycosidesPharmacokinetics Bactericidal Safe in pregnancy Dosage needs to bereduced in cases ofimpaired renal function. 9. This class includes:- Macrolides- erythromycin, clarithromycin, azithromycin Lincosamides- clindamycin Aminoglycosides- gentamicin, tobramycin, amikacin,netilmicin,neomycin, streptomycin. Tetracyclines- tetracycline, doxycycline,minocycline Chloramphenicol 10. Pharmacokinetics: Bacteriostatic Dose adjustment in renalfailure is not necessaryAdverse Effects : GI upset Cholestatic jaundice Prolongation of QT interval(erythromycin) Theophylline, oral anticoagulantscannot be administeredsimultaneously 11. PharmacokineticsPharmacokinetics Bectericidal Negligible oral absorption Dose adjustment iscritical in renalimpairmentAdverse Effects Ototoxic (permanent)Avoid concurrent use ofother ototoxics drugs for eg.Lasix , minocycline Nephrotoxic ( reversible):use cautiously with othernephrotoxic drugs 12. PharmacokineticsBacteriostaticBest oral absorption in fastingstate Adverse Effects Contraindicated in renal failure(except doxycycline and minocycline) Nausea, diarrhoea Binds to metallic ions in bones and teeth (tobe avoided in children andin pregnancy) Phototoxic skin reactions 13. This group includesThis group includes :: Sulphonamides: Sulfamethoxazole, sulfadoxine Trimethoprim Quinolones: Ciprofloxacin, levofloxacin, pefloxacin, ofloxacin, norfloxacin,gatifloxacin, moxifloxacin, sparfloxacin RifampicinAzoles: This group includes- Antibacterial- Metronidazole, secnidazole, tinidazole, Antihelminth- Albendazole, Mebendazole, thiabendazole 14. Pharmacokinetics Bactericidal Well absorbed orally withgood bioavailability Dose reduction necessary inrenal failureAdverse Effects Fatal marrow dysplasia andhaemolysis in G6PDdeficiency Skin and mucocutaneousreactions: Stevens- Johnsonsyndrome Contraindicated inpregnancy 15. Pharmacokinetics Bectericidal Well absorbed after oraladministration Dose adjustment requiredin renal impairment(except moxifloxacin and trovafloxacin) These two drugs arecontraindicated in hepaticAdverse Effects GI side effects CNS effects such as restlessness,headache, insomnia, confusion andseizures in the elderly Rare skin reactions Should be avoided in pregnancy Not routinely recommended for use inpatients under 18 yearsof age 16. Pharmacokinetics Almost completelyabsorbed after oraladministration (60% afterrectal administration).Adverse Effects Metallic taste Severe vomiting if taken withalcohol (disulfiram likesyndrome ) 17. CNS: Meningitis, brain abscess etc Respiratory: URTI, Pneumonia, Lung abscess, Bronchiectasis CVS: Acute rheumatic fever, Infective endocarditis GIT and HBS: Cholera, Bacillary dysentery, Enteric fever,gastroenteritis, peritonitis,liver abscess Genitourinary: UTI, pyelonephritis, STDs Skin : Cellulitis necrotizing fascitis Musculoskeletal: Osteomyelitis, Septic arthritis Mycobacterial Infections: Tuberculosis, Leprosy Chlamydial Infections Systemic Infections: Sepsis syndrome 18. 62 year old male presents to your clinic with c/o: Cough withexpectoration x 4days Intermittent fever, measured to 100.8 Chest pain Rt side PMHx Healthyo No H/O hospitalization in recent pasto not on any medication Drink socially , non smoker 19. ExamVS temp 100.3, P 92, RR 18, Spo2 - 96% on room air, BP123/75HEENT normalNeck normal w/o palpable LN or TMGLungs Bronchial breath sound in I/S , I/A on Rt side, clear atbases,CV normalLegs no edema 20. Case 1 21. Community acquired Pneumonia (CAP) Recent onset of- Fever- Productive cough- TLC- CXR Why CAP- Healthy adult with no H/O hospitalization in recent past& was not taking any antibiotics 22. Common Outpatient Bacterial Etiologies 23. AntibioticsAntibiotics Oral macrolide Erythromycin Azithromycin ClarithromycinThis patients pneumonia is mildPreviously healthyNo antibiotics in past 3 months 24. In patients who are older, have comorbid illnessesLevofloxacin Moxifloxacin In patients treated with antibiotics within the last 90 days. Respiratory quinolonesMoxifloxacinLevofloxacinGemifloxacinor B- lactamAmoxicillin + ClavunateCefuroxime 25. Beta-lactam + macrolideCeftriaxone or cefotaximeErythromycin, azithromycin, or clarithromycinOR Fluoroquinolone with antistreptococcal activityLevofloxacin or moxifloxacin 26. Trimethoprim/sulfamethoxizole x 3 dayswomen with risk factors, complicated UTIFluoroquinolone x 3 days: Ciprofloxacin Norfloxacin OfloxacinNitrofurantoin x 7 days 27. Initial drug selections:FluoroquinolonesCiprofloxacinLevofloxacinCephalosorinCeftriaxoneCefotaxime+ Amikacin 28. 57 years male painful rash on his right leg. 5 daysago he developed a blister on his foot after wearing anew pair of shoes.c/o fever with chills PMHx COPD, high cholesterolSocial stopped tobacco two years ago. 29. Exam Temp 101.2 otherwise stable , APPP Exam unremarkable except for Lungs few inspiratory rales Right leg 30. Outpatient Treatment: non-MRSAAntistaphylococcal penicillinDicloxacillinFirst-generation cephalosporinCephalexin Inpatient Treatment: non-MRSA Amoxicillin + Clavunate Clindamycin is a good alternate with penicillin allergy Surgical opinion 31. A 43 year old male presents with 10 days of purulentrhinorrhea, subjective fevers, and facial headaches. PMHx HTN, high cholesterol Meds lisinopril/HCTZ FamHx noncontributory 32. Exam HEENT VS normal tenderness over right maxillary sinus Exam otherwise unremarkable Diagnosis? Sinusitis 33. Mild Acute Bacterial Sinusitis (ABS)AmoxicillinAmoxicillin/clavulanateCefuroxime axetilCefpodoximeOrantistrep. fluoroquinolones:LevofloxacinMoxifloxacin 34. Drug option in the case of allergies to penicillinand cephalosporin with Mild ABS: Doxycycline Trimethoprim/sulfamethoxizole Azithromycin Clarithromycin 35. Drug option in the case of allergies to penicillin andcephalosporin with Moderate to Severe ABS: Antipneumococcal fluoroquinolone: Levofloxacin Moxifloxacin 36. 42 years male with 5 days of progressive diffuseheadache, mildly stiff neck,fever vomiting, confusion.PMHx none knownPSHx - none 37. Exam VS: T 100.9, Pulse 96, RR 16, BP 138/82 Gen: mildly ill appearing Mental status: orientation to place & person not time HEENT: mild photophobia Neck: mild pain with flexion (kernig sign +ve ) Skin: no rash 38. Lab.- TLC - 16000 DLC - N80 L18 CECT Head - normal study CSF - TLC 412DLC N 96 L4protein 110mg/dlsuger - 23 mg/dl 39. Adults(3 months old: High dose ceftriaxone or cefotaxime+ Vancomycin 1gm IV BD Adults > 55years of age , patient with alcoholismor other debilitating illness High dose ceftriaxone /cefotaxime+ Vancomycin 1gm IV BD+ Ampicillin 2gm/ 4horly2gm IV BD 40. Cholera:Tetracycline 250 mg 6-hourly for 3 days,Doxycycline 300 mg single dose or Ciprofloxacin 1g in adultsBacillary Dysentery:Ciprofloxacin 500 mg 12-hourly for 3 daysHelicobacter pylori Infection:Two antibiotics (from amoxicillin, clarithromycinand metronidazole) for 7 days 41. Aetiology: Salmonella typhi and Salmonella paratyphi A and BCiprofloxacin 500 mg 12-hourlyOfloxacin 400 mg every 12 hourlyCeftriaxone 2gm IV BDAzithromycin 1gm once daily x 5 daysTreatment should be continued for minimum 10 days.Or5 days after resolution of fever 42. Aetiology (pyogenic): E.coli, various streptococci(amoebic): Entamoeba histolytica Management:o Pyogenic: Combination of antibiotics e.g3rd gencephalosporin, gentamicin and metronidazoleo Amoebic: Metronidazole (800 mg 8-hourly for 10 days)or tinidazole (2 g daily for 3 days)Luminal amoebicide-diloxanide furoate (500 mg 8-hourly for 10 days) 43. Gastro-Intestinal:Ancylostoma, Ascaris:Albendazole 400 mg single dose or Mebendazole 100mg 12 hourly for 3 daysTissue parasite:Filariasis: Caused by Wuchereria bancrofti Treatment: Diethylcarbamazine 6 mg/kg body wt.orally in 3 divided doses for 12 days. 44. Avoid tetracycline Staining of teeth and bones in babies Acute yellow atrophy of lever , pancreatitis in mother Avoid sulfa drugs in the third trimester May be associated with kernicterus Avoid aminoglycosides Kidney toxicities Can cause foetal ear damage FluoroquinolonesConcerns about cartilage development 45. Treat the Mother first and the baby will appreciate it Penicillins and cephalosporins are generally safe inpregnancy. Macrolides are generally safe- They may increase nausea early on 46.