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Newer Antibiotics Newer Antibiotics NEWER ANTIBIOTICS NEWER ANTIBIOTICS B-LACTAMS QUINOLONES CEPHALOSPORINS LEVOFLOXACIN SPARFLOXACIN CEFDITOREN GATIFLOXACIN CEFEPIME GREPOFLOXACIN CEFEPIROME TRAVOFLOXACIN CARBAPENEMS MOXIFLOXACIN ERTAPENEM CLINAFLOXACIN MACROLIDES OXAZOLIDINONES DIRITHRMYCIN LINEZOLID STREPTOGRAMINS JOSAMYCIN DALFOPRISTIN AMINOGLYCOSIDES QUINPRISTIN ARBIKACIN GLYCO/LIPOPEPTIDES DAPTOMYCIN ORITAVANICIN GLYCINCYCLINS TEGICYCLINS CEPHALOSPORINS • The activity of cephalosporins increases over gram negative organisms as the generation passes • 4th generation are even resistant to b-lactamases and highely active against pseudomonas • They act by inhibiting cell wall synthesis • INDICATION DOSAGE :cefditoren at 200-400mg po12hly indicated for bronchitis, complicated sinusitis,otitis media,uti cefepime at 500-2g iv 8-12hly indicated for empirical therapy in febrile neutropenic patients and ABR gram-ve bacteremia • ADVERSE EFFECTS:git effects, thrombophlebitis(cfepime), rare ones like hypersensitivity,interstitial nephritis,anemia, leukopenia • CONTRAINDICATIONS: Decreased dosage in renal failure .cefepirome contra in pregnancy lactating .cefepime is to used with caution in lactating patients QUINOLONES • The activity of quinolones increases over gram +ve organisms as the generation increases .4th generation drugs are active against even anaerobic organisms • INDICATIONS: levofloxacin(250-750mg po od)for sinusitis, bronchitis, pneumonia, uti . Gatifloxacin(400mg po/iv od 7-14days) for LRTI,UTI, gonorrhea .moxifloxacin(400mg po/iv od) for sinusitis,bronchitis ,pneumonia • ADVERSE EFFECTS :most well tolerated drugs .nasuea ,rashes, cns disturbances . • INTERACTIONS: increases QT interval • CONTRAINDICATIONS:2nd,3rd generation decrease dosage in renal failure .4th generation decrease dosage in hepatic failure • Not to used in pregnancy lactating children below 18yrs GLYCINCYCLINS(TEGICYCLIN) • Bacteriostatic drug having good activity against gram+ve and gram – ve organisms • Activity similar to tetracyclins • Inhibits protein synthesis by binding with 30s subunit • INDICATION: complicated skin&intra abdominal infections caused by susceptable strains • DOSAGE:100mg stat followed by 50mg every 12th hly IV for 5-14days • ADVERSE EFFECTS: git side effects, irritation at injection site ,photosensitivity • INTERACTIONS: decreased elimination of warfarin • CONTRAINDICATIONS: not safe in pregnant lactating and children below 8 yrs KETOLIDE(TELITHROMYCIN) • Telithromycin has broad spectrum of activity against gram +ve bacteria ,active against most macrolide resistant pneumococci, but like erythromycin not active against staph aureus • INDICATION: for sinusitis, bronchitis , pneumonia • DOSAGE:800mg od daily dosage • ADVERSE EFFECTS: git side effects , vision problems , hepatotoxicity, pseudomembrane colitis • INTERACTIONS: inhibitor of cyp3a4 • CONTRAINDICATIONS: decreased dosage in hepatic failure, no data for pregnant, lactating, children OXAZOLIDINONES(LINEZOLID) • Outstanding activity against variety of gram positive organisms • Linezolid prevents formation of the 70S ribosome complex • No cross resistance • INDICAT/DOSAGE: at 10mg/kg iv/po for 10-14days is used as an alternative to vancomycin for MRSA pneumonia/enterococcal meningitis • Adverse effects: git side effects /oral moniliasis/ taste perverstion thrombocytopenia / myelosupression • Contraindications: pregnancy/lactation-caution .FDA has approved for treating infections in infants .NO contraindication in renal, hepatic failure • Interactions: MAO inhibitor STREPTOGRAMINS (DALFOPRISTIN-QUINPRISTIN) • Good activity against MDR gram +ve organisms except enterococcal feacalis active against gram –ve URT pathogens • Inhibits protein synthesis by binding to 50s ribosome • Both are static drugs individually but cidal when used in combination, • StreA:streB—30%:70% • INDICATION: VRSA ORSA VR enterococcal feacium infections • DOSAGE: 7.5mg/kg IV ever 8-12hly for 7das • ADVERSE EFECTS: thrombophlebitis, arthralgias ,myalgias • INTERACTIONS: inhibits cyt p3a4 • CONTRAINDICATIONS: hepatic failure , not safe in children pregnant ,lactating women GLYCO/LIPOPEPTIDE (DAPTOMCIN) • Bactericidal activity against wide variety of gran +ve bacteria including enterococi,staphylococci,streptococci that are even resistent to methicillin& vancomycin • Daptomycin bind to bacterial mambrane causes rapid depolarisation of membrane potential resulting in inhibition of dna rna protein synthesis • INDICATION: at dose of 4mg/kg iv od is approved for treatment of complicated skin infections • ADVERSE EFFECTS: git side effects , increased LFTS ,increased CPK with or with out myopathy • CONTRAINDICATIONS: renal failure ,inpregnant and lactitating no data CARBAPENEMS(ERTAPENEM) • Effective against gram –ve bacteria and anaerobic bacteria • It inhibits cell wall synthesis • INDICATION: indicated only for community acquired infections because of its lack activity against pseudomonas • DOSAGE:1gm iv once aday • ADVERS EFFECTS: diarrhoea • seizeures(older,renal failure,cns pathology) • pseudomembrane colitis • CONTRAINDICATIONS: renal failure, no data in pregnant lactating and children Why? •Increasing resistance patterns among both community and hospital acquire infections •Judicious use will prevent resistance strains to emerge INDICATIONS 1.Clinical scenario 2.Organisms common in that scenario 3.Antibiotic resistance patterns 4.Pharmacokinetics of the drug 5.Clinical trials Community infections •Pneumonia •Meningitis •Osteomyelitis COMMUNITY ACQUIRED PNEUMONIA Core pathogens •Streptococcus pneumonia •Mycoplasma pneumoniae (during epidemics) •Haemophilus influenzae •Staphylococcus aureus •Chlamydia pneumonia •Legionella pneumophila Pencillin resistance is a major problem in these cases So the drug used should take into account of the organism, risk factors for atypical organisms,anti biotic resistance With no risk factors • Patient can be treated with • Ketolides(telithromycin) • New extended spectrum fluroquinolones • Ertapenem if there is e/o of vancomycin resistance Fluoro quinolene should not be used in patients with Rhinitis,sinusitis,Pahryngitis unless there is evidence of pneumonia……………ACP recommendation. Meningitis Mc organisms • Strep.pneumoniae • H.influenza • Neisseria meningitidis • Streptococcus agalactiae • Listeria monocytogenes Pencillin resistance is also major problem So empirical therapy is started with 3rd generation cephalosporins But if risk factors are present for listeria ampicillin with gantamycin should be used as empirical therapy Cephalosporins are ineffective AFTER GRAM STAIN AND CULTURE EMPIRICAL THERAPY CAN BE CHANGED TO MORE SPECIFIC THERAPY In adults penetration of vancomycin is not good especially if dexamethasone is being used So in such cases ceftriaxone plus rifampcin is used Newer antibiotic LINEZOLIDE irrespective of dexamethasone therapy reaches high concenteration in CSF fluid so can be used in stead of ceftriaxone +rifampcin Osteomyleitis Acute haematogenous infection : Staph.aureus Secondary to contagious focus of infection Polymicrobial: staphylococci, streptococci, enteric organisms, and anaerobic bacteria. P. aeruginosa is frequently associated with puncture wounds of the foot (especially by a nail through a sneaker) Penicillin-resistant, methicillin-sensitive (MSSA ) --- ceftriaxone, 1 g IV q24h Methicillin-resistant (MRSA ) --- Vancomycin Vancomycin alone always not effective in such cases. Rifampcin can be added New antibiotics like daptomycin is effective osteomyelitis due to Enterobacteriaceae ---- Extended spectrum β-lactam antibiotics fluoroquinolone Hospital acquired infections Most common are •UTI •Pneumonia •Surgical site infections UTI Mc organisms are E.coli, enterobacteracea enterococci pseudomonas Risk factors for uti include catheterization,instrumentation,diabetes Most are resistant to tmp-smx,amoxiciliin In such cases Fluroquinolones, extende spectrum b-lactams likeTicarcillin Carbapenem—(Imipenem) Fosfomycin has been recently approved for uncomplicated UTI Hospital acquired pneumonia Most common organisms are ; •Pneumococcus •Staph areus •Enterobacteriacea •Pseudomonas •Anaerobes Many are resistant to pencillin, Enterobacteriacea are resistant to cephalosporins Pseudomonas to cephalosporins,pencillin HAP is classified into 3 types based on risk factors and severity of pneumonia And the time of development of pneumonia(<5days >5days) 1.Moderate to MILD ,early onset, no risk factors treated like CAP Rx: 3rd generation cephalosporins or fluroquinolones 2.Moderate to severe,early onset, if risk factor present additional antibiotic is added If risk factors … Anaerobes…… Clindamycin Pseudomonas Extended spectrum Blactam+aminoglycoside Staph.aureus Vancomycin,linezolid,ortitavanicin Entero bacteriacea cephamycins 3.Severe H.A.P Use amino glycoside with carbapenems or extended blactams Surgical site infections Most common G+cocci. Staphyloccoccus aureus, Staphylococcus epidermidis, Enterococcus faecalis and Escherichia coli, the latter two of which are common pathogens after clean-contaminated surgery. Antibiotic chosen should be active against Staph 1 generation cephalosporins CEFAZOLIN commonly used The antibiotic should be given within two hrs of sugery Single dose prophylaxis is enough Unless if the patient is undergoing transplant surgery(48 hrs) Immunocompromised Individuals Patients with neutropenia neutropenia is common in hematological malignancies: Such patients predisposed to both gram +Coagulase – staph Stre. viridans and g- infections Especially to pseudomonas Patient
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