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![IMIPENEM :
› Imipenem has a broad spectrum of activity
against aerobic, anaerobic[Gram-positive and Gram-
negative bacteria], It is particularly important for its activity
against Pseudomonas aeruginosa & Enterococcus faecelis.
› It is not active against MRSA,e faecium,
sternotropho,burkhlodheria,flavobacterium
› Imipenem is rapidly degraded by the renal
enzyme dehydropeptidase 1,so, is almost always coadministered
with cilastatin to prevent this inactivation.
› Indicated for cSSSI,LRTI,IAI,UTI
› DOSES : 500mg Q6h to 1gm TDS
› At high doses, imipenem caused myoclonus, seizures.](https://image.slidesharecdn.com/antibioticsinicu-180505115322/75/Antibiotics-in-icu-9-2048.jpg)
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Antibiotics in icu
- 1. ANTIBIOTICS IN ICU DrImran Gafoor Consultant intensive care medicine RKCH,Raipur (CG) april 2018
- 4. Barriers to timely antibiotics Delayed recognition of sepsis and septic shock • Infection • Hypotension Inappropriate antimicrobial therapy • Failure to use stat order • Unrecognized risk factors for MDR pathogens • No specifications for order of administration • Logistical delays Crit Care Clin 2011;27:53-76
- 5. Risk Factors MDR/Health-care associated pathogens Fungemia •broad spectrum antibiotics within 90 d • hospitalization >5 d • local high antibiotic resistance rates • residence in LTCF • chronic dialysis within 30 d • home wound care • family member with MDR infection • mechanical ventilation ≥5 d • immunosuppression • structural lung disease • IV drug use • COPD (Pseudomonas spp.) • Influenza infection (MRSA) • broad-spectrum antibiotics • central venous catheter • parenteral nutrition • renal replacement therapy in ICU • neutropenia • hematologic malignancy • implantable prosthetic devices • immunosuppression • chemotherapy Clin Infect Dis 2007;44:S27-72 Am J Respir Crit Care Med 2005;171:388-416 Clin Infect Dis 2009;49:1-45 Clin Infect Dis 2009;48:503-35
- 6. Below Figure describesthe most important antibiotic pharmacokinetics and pharmacodynamics parameters. These are the percentage of time that the antibiotic concentration remains above the minimum inhibitory concentration (T > MIC), the ratio of peak concentration to MIC (Cmax/MIC), and the ratio of the area under the concentration–time curve to MIC (AUC/MIC) T > MIC predicts the efficacy of time-dependent antibiotics (Fig). The ideal concentration is 2–4-fold the MIC of the pathogen throughout the dosing interval. T > MIC can be optimized by increasing antibiotic dose or frequency or using continuous or extended infusions . The Cmax/MIC predicts the efficacy of concentration-dependent antibiotics (Fig). Cmax is dependent on the dose and is inversely related to Vd. The AUC24h/MIC predicts the efficacy of antibiotics with mixed properties (Fig). AUC24h/MIC can be optimized by increasing the antibiotic dose. Obesity may decrease T > MIC, Cmax/MIC, and AUC24h/MIC mainly by affecting antibiotic Vd and clearance
- 7. Piperacillin tazobactam(BL/BLI) › pneumonia,peritonitis,diabetic foot,IAI,febrile neutropenia (empiric therapy),BSI in neutropenic cancer patients › Dose : 4.5 gm iv Q6H or 3.375 gm Q4H (2.25 gm Q6H if Crcl<40) › Empirical coverage CA aspiration pneumonia : c tri + clinda › empirical nosomial aspiration coverage : piptaz + aminogly,
- 8. MEROPENEM › meropenem isbactericidal except against listeria (bacteriostatic) › covers gram – including ESBL,gram +;e faecalis,anaerobes › meropenem is more active against enterobacteriacea & less active against gram + (as compared to imipenem) › Approved for cSSSI,intra abdominal infections,meningitis › DOSE : cSSSI,CAP– 500 mg TDS › IAI ,febrile neutopenia– 1 gm TDS › Seizures have been reported, most commonly in patients with CNS disorders (eg, brain lesions, history of seizures) or bacterial meningitis or compromised renal function
- 9. IMIPENEM : › Imipenemhas a broad spectrum of activity against aerobic, anaerobic[Gram-positive and Gram- negative bacteria], It is particularly important for its activity against Pseudomonas aeruginosa & Enterococcus faecelis. › It is not active against MRSA,e faecium, sternotropho,burkhlodheria,flavobacterium › Imipenem is rapidly degraded by the renal enzyme dehydropeptidase 1,so, is almost always coadministered with cilastatin to prevent this inactivation. › Indicated for cSSSI,LRTI,IAI,UTI › DOSES : 500mg Q6h to 1gm TDS › At high doses, imipenem caused myoclonus, seizures.
- 10. TEICHOPLANIN : › usedin the prophylaxis and treatment of serious infections caused by Gram-positive bacteria, including methicillin- resistant Staphylococcus aureus and Enterococcus faecalis. It is a semisynthetic glycopeptide antibiotic with a spectrum of activity similar to vancomycin. › It is not suitable for use as a single agent › Inherently resistant to gram- & atypical bacteria › doses: Initially, 6 mg/kg on first day, followed by 3 mg/kg/day. Severe infection: 6 mg/kg every 12 hr for the 1st 3 doses followed by 6 mg/kg/day.
- 11. VANCOMYCIN › for serious,life-threatening infections by Gram- positive bacteria › for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, and meningitis caused by methicillin-resistant S. aureus › Only oral indication : Clostridium difficile colitis(125 mg Q6h) › Toxicity is best monitored by looking at trough values(15-20 mg/L) › red man syndrome or red neck syndrome : flushing and/or an erythematous rash that affects the face, neck, and upper torso (T/t : antihistamines,slow infusion) › Usual dose: 500 mg IV q6hr or 1 g IV q12hr
- 12. CLINDAMYCIN › Clindamycin isused primarily to treat anaerobic infections including dental infections, respiratory tract infections, skin & soft tissue infections, peritonitis › It is of the lincosamide class and works by blocking bacteria from making protein(bacteriostatic) › Most aerobic Gram-negative bacteria (such as Pseudomonas, Legionella, Haemophilus influenzae and Moraxella) are resistant to clindamycin, as are the facultative anaerobic Enterobacteriaceae(except capnocytophaga) › Clindamycin may be useful in skin and soft tissue infections caused by MRSA › SE :CDAD, Pseudomembranous colitis (potentially lethal) › Clindamycin has BLACK BOX warning for CDAD › Dose : 150-450 mg PO q6-8hr,600 mg iv TDS( not to exceed 1.8 g/day)
- 13. LINEZOLID › Linezolid isactive against most anaerobic Gram-positive bacteria including streptococci, VRE,MRSA › for VRE(faecium) ;MRSA nosocomial pneumonia,MRSA CAP; cSSSI including diabetic foot(septran +clinda??) , complicated by osteomyelitis,gram + CRBSI › “reserve antibiotic” › Linezolid is considered bacteriostatic › post-antibiotic effect(bacterial growth is temporarily suppressed even after the drug is discontinued) › Dose : 600 mg PO/IV q12hr for 10-14 days
- 14. › Linezolid canbe taken by mouth › SE :antibiotic candidiasis( thrush and vaginal candidiasis ), pancreatitis, transamnitis,reversible thrombocytopenia if taken › 14 days,irreversible peripheral neuropathy,lactic acidosis,optic neuritis (??avoid›28 days) › Serotonin syndrome with SSRIs, SNRIs, TCAs, MAOIs ,cheese,alcohol,smoked/pickled food
- 16. COLISTIN :OR polymyxinE (bactericidal FOR GRAM -) It remains one of the last-resort antibiotics for multidrug- resistant Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter,MDR enterobacteriacea Inherently resistant : › Brucella,Moraxella,morgenella,neisseriae › Burkholderia cepacian,proteus,serratia,providentia › Chryseobacterium indologenes,h pylori › Edwardsiella,some sternotrophomonos strains › Elizabethkingia meningoseptica › Francisella tularensis spp. › Gram-negative cocci
- 17. › Toxicity :neuro/nephro (both transient & reversible), bronchospasm for nebulized form (salbutamol??) DOSING : Cr 1.3-1.5 → 2MU TDS inhalational colistin : Cr 1.6-2.5 → 2MU BD ‹40 kg : 0.5 MU BD Cr ≥ 2.6 → 2 MU OD › 40 kg : 1 MU BD 2 MU after each HD recurrent/severe : 2MU TDS 2 MU daily during PD 2 MU TDS during CRRT ISCCM critical care update 2017
- 18. POLYMYXIN B › Ithas a bactericidal action against almost all Gram-negative bacilli except Proteus & Neisseria › Used for UTI, meningitis(only intra thecal), and BSI caused by pseudomonos,klebsiella,e coli › Dose :15,000 to 25,000 units/kg body weight/day(15L stat f/b 7.5L BD);if crcl < 20 give half dose › SE : neurotoxicity and acute renal tubular necrosis
- 19. Has the capacityto cross BBB has in vitro activity against MRSA,CRE(KPC),pseudomonos(XDR) studies suggest poly B +fosomycin has reduced ototoxicity dose : 4gm iv Q6h
- 20. TIGECYCLINE It’s Glycylcycline (tetracyclinederivative) Licensed for complicatated SSSI(excluding diabetic foot), complicated IAI,CAP targets both Gram-positive and Gram-negative bacteria It has no activity against Pseudomonas or Proteus Black box warning: use only when alternative treatment is not suitable (↑mortality in HAP/VAP) Dosing : 100 mg bolus f/b 50 mg BD only dose modification is child pugh C (25 mg BD )
- 21. Trimethoprim-sulfamethoxazole/ cotrimoxaxazole/septran › doesn’t acton Pseudomonos,mycoplasmae,francisella › Used for sternotrophomonos › 20 mg TMP/kg/day IV divided q6hr in severe sepsis › Causes pseudo elevation in creatinine
- 22. Cefepime › fourth-generation cephalosporin, ›Not a β lactamase inducer;lower affinity for β- lactamase › for e coli & pseudomonos › Nosocomial pneumonia ,empirically for febrile neutropenia,complicated UTI,cSSSI.cIAI (+metronidazole) › Dose : 2 gm iv TDS (moderate infection 2 gm BD) › Can cause : NCSE,reversible encephalopathy › CEPHALOSPORINS ARE NOT ACTIVE AGAINST MRSA,ENTEROCOCCUS,STERNOTROPHOMONOS
- 23. Sulbactam › irreversible inhibitorof β-lactamase › not able to interact with the AmpC cephalosporinase so little protection against bacteria such as Pseudomonas aeruginosa, Citrobacter, Enterobacter, and Serratia, which often express this gene. › Resurgence for acineto septicemia › Dose : 2 gms iv tds (max 8 gms daily)
- 24. Amikacin › Acts onmultidrug-resistant, aerobic Gram-negative bacteria, especially Pseudomonas, Acinetobacter, Enterobacter, E. coli, Proteus, Klebsiella, and Serratia(only gram + affected are nocardia & staphylococcus) › BLACK BOX WARNINGS :Causes ototoxicity(viii cranial n,permanent),neurotoxicity,nephrotoxicity(proximal tubules damage,hypoK,avoid Lasix??),neuromuscular weakness(Ca salts might be helpful??) Dose :20 mg/kg/day IV; may administer with antipseudomonal beta- lactam or carbapenem May be effective in genta/tobra resistant gram - GENTAMICIN Dose : 4-7 mg/kg/day Gentamicin is not used for Neisseria or legionella (risk of endotoxin septicemia)
- 25. Metronidazole › antibiotic ,antiprotozoal medication for abscesses in the liver, pelvis, abdomen, and brain caused by susceptible anaerobic bacteria › mild-to-moderate Clostridium difficile colitis if vancomycin or fidaxomicin is unavailable › SE : Disulfiram like drug interaction with alcohol,propylene glycol
- 26. Levofloxacin : respiratoryquinolone › for CAP,CAUTI (first line T/t), VAP,HCAP,prostatitis,IAI › moxi & ampho B are not cleared by HD › Gemi/moxi is anti MRSA-levofloxacin isn’t › Levoflox needs renal adjustment;moxi doesn’t › levofloxacin exhibits greater activity towards Gram + but lesser activity toward Gram - especially Pseudomonas aeruginosa › Levo > moxi for acineto › C/I : epilepsy, Avoid with NSAIDS & QT prolongers (atypical antipsychotics,TCA) › SE : black boxed – tendinitis , Irreversible peripheral neuropathy, seizures & psychiatric issues,myasthenia exacerbation,S-J syndrome,hepatitis › Dose : 750 mg PO/IV once daily for 7-14 days
- 27. Azithromycin/clarithromycin › It inhibitssome Gram +, some Gram - & many atypical bacteria. › For CAP,PID › Dose azithro : iv 500mg OD for 7 days › Dose : clarithro 500mg BD › FDA warning : avoid in long QT,slower heart rate, (arrthymia??) › Clarithromycin has ↑ gram + activity than azithro › Azitro is more active against chlamydia trachomatisss › Azithro has ↑ gram – activity than clarithro
- 28. Amoxicillin/clavulanic acid(augmentin) › Usedin : CAP,UTI,LRTI,SSI,animal & human bites › SE : oral candidiasis,diarrhea,cholestatic jaundice › Dose : 1.2 gm IV TDS
- 29. MINOCYCLINE › FDA approval: MDR acineto, Burkholderia cepacia, Stenotrophomonas maltophilia. › Dose : 200 mg bolus f/b 100 mg BD › No dose modifications › minocycline contains magnesium sulphate (renal impairement ?? Heart blockage ??) › Has anti anabolic actions (BUN/creatinine ??)
- 31. › Antibiotics activeagainst MRSA : vancomycin,daptomycin,linezolid,Bactrim,clindamycin,minocy cline,tigecycline,doxycycline,rifampin › Antibiotics active against stenotrophomonos : Bactrim,cefepime,minocycline,tigecycline,levoflox,polymyxin › Acineto VAP : meropenem + colistin + sulbactam(/tigecycline) {ertapenem,Fosfomycin doesn’t act against acineto} › Antibiotics active against morgenella : cefepime,pip- tz,gentamycin,meropenem,aztreonam,levoflox
- 32.