majorly used antibiotics in icu

1. ANTIBIOTICS IN ICU
Dr Imran 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 describes the 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 is bactericidal 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 :
› 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.

10. TEICHOPLANIN :
› used in 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 is used 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 is active 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 can be 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 polymyxin E (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
› It has 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 capacity to 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 (tetracycline derivative)
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 act on 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 inhibitor of 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 on multidrug-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 : respiratory quinolone
› 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 inhibits some 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)
› Used in : 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 active against 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. MENINGOENCEPHALITIS( Icu protocols)