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Review of AntibioticsReview of Antibiotics
Zagorka Popovski, Pharm.D.
Clinical Pharmacist, Intensive Care
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CephalosporinsCephalosporins
Gram +
1st Generation
•Ancef
•Keflex
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LESS IS MORE!!!LESS IS MORE!!!
Timing of pre op antibiotic is key
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POPOVSKI and TEOHPOPOVSKI and TEOHSCCM 1993 SAN DIEGO CASCCM 1993 SAN DIEGO CAREDUCTION OF POST-OP
ANTIBIOTICS FROM 72 HR TO 48HRADMINISTER PRE-OP ANTIBIOTIC IN
ORWOUND INFECTION RATE REDUCED
FROM 2% TO 0.6%
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CephalosporinsCephalosporins
Gram + Gram + Coverage plus:
1st Generation •Ecoli
•Ancef •Proteus
•Keflex •Klebsiella
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CephalosporinsCephalosporins
Gram + 1st Generation 2nd Generation
•Ancef •Cefuroxime •Keflex •Cefamandole
•Cefotetan +/- anaerobe•Cefoxitin
H Flu
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CephalosporinsCephalosporins
Gram + Gram -
1st Generation 2nd Generation 3rd Generation
•Ancef •Cefuroxime •Ceftriaxone
•Keflex •Cefamandole •Cefotaxime
•Cefotetan •Ceftazidime
•Cefoxitin
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CephalosporinsCephalosporins Gram - Gram - Coverage *3rd Generation Acinetobacter
Serratia •Ceftriaxone (CNS penetration, gram neg.
alternative to amnioglycosides)•Cefotaxime
•Ceftazidime •Pseudomonas Aeruginosa
*not for enterobacter
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PenicillinsPenicillins
Penicillin Ampicillin Cloxacillin
Amoxillin Oxacillin
Nafcillin
Methicillin
®
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PenicillinsPenicillins Coverage
•Ampicillin •Enterococcus•Amoxicillin •Ecoli
•Klebsiella•Proteus•H. Flu
Clavulin®=amoxicillin+clavulinic acid
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Antipseudomonal PenicillinsAntipseudomonal Penicillins
Piperacillin (Pipracil)Piperacillin/Tazobactam (Tazocin)Ticarcillin (Ticar)Ticarcillin/Clavulante (Timentin)
Gram +/- (including Pseudomonas a.)
*anaerobic coverage
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+
R
R
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PenicillinsPenicillins
CloxacillinOxacillinNafcillinMethicillin
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CarbapenemsCarbapenems
Imipenem + Cilastatin (Primaxin)Meropenem (Merrem)Ertapenem (Invanz)
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MeropenemMeropenem
Very broad spectrum Gram negative including pseudomonas gram positive including staph and enterococcus Anaerobes
Indicated for “high-severity” intra-abdominal infections
Replaced imipenem//cilastatin at HHS
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5 7 15 30
FAILURE
A.P.A.C.H.E.
Imipenem
AA + AMG
Christou & Solomkin, 1990
(Intra-abdominal sepsis)
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Activity of Study Agents Against Activity of Study Agents Against Facultative Gram-Negative BacteriaFacultative Gram-Negative Bacteria
Bacteria
TobramycinMIC
ImipenemMIC
90 Resistant90 Resistant
E.Coli
Enterobacter
Klebsiella
Proteus
Pseudomonas a.
Citrobacter sp.
Other Gram Negative
Breakpoint…Tobramycin 4
Imipeneim 4
4.0
1.0
1.0
1.0
4.0
16.0
2.0
5
0
0
0
1
2
0
0.25
1.0
1.0
4.0
2.0
0.5
4.0
0
0
0
1
0
0
0
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Activity of Study Agents Against Common Activity of Study Agents Against Common Anaerobic BacteriaAnaerobic Bacteria
Bacteria
ClindamycinMIC
ImipenemMIC
90 Resistant90 Resistant
ß. Fragilis
Bacteroides sp.
Clostridia sp.
Enterococci
Breakpint…Clindamycin 2
Imipenem 4
16.0
16.0
4.0
-
?
?
4
-
0.50
0.50
2.0
4.0
0
0
0
0
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CONDITIONS FOR WHICH CONDITIONS FOR WHICH THERAPEUTIC ANTIBIOTICS (24h) ARE THERAPEUTIC ANTIBIOTICS (24h) ARE
NOT RECOMMENDEDNOT RECOMMENDED Traumatic and iatrogenic enteric perf’n operated
on within 12h Gastroduodenal perf’n operated on within 24h Acute/gangrenous appendicitis without perf’n Acute/gangrenous cholecyswtitis without perf’n Transmural bowel necrosis from
embolic,thrombotic or obsstructive vascular occlusion without perf’n or established peritonitis or abcess
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FluoroquinolonesFluoroquinolones
Nalidixic acid (NegGram)Ciprofloxacin (Cipro)Norfloxacin (Noroxin) Levofloxacin (Levaquin)Gatifloxacin (Tequin)Moxifloxacin (Avelox)
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FluoroquinolonesFluoroquinolones
Ciprofloxacin (Cipro) - Ps. a.Norfloxacin (Noroxin)Levofloxacin (Levaquin) Gatifloxacin (Tequin) Moxifloxacin (Avelox)
CAP
Strep.
+ other gram neg atypicals
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FluoroquinolonesFluoroquinolones
Advantages (Bioavailability, IV/PO, tissue penetration)
Drug Interactions (Calcium, Iron, Magnesium)
(Theophylline,Methylxanthines)
Side Effects
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AminoglycosidesAminoglycosides
Gentamicin TobramycinAmikacin
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Aminoglycosides
MIC Serratia (Pseudomonas a.)
Gentamicin .5 2
Tobramycin 2 .5
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OthersOthers
VancomycinLinezolidSeptra
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SAVING ANTIBIOTICS SAVES SAVING ANTIBIOTICS SAVES LIVES!!!LIVES!!!
PRINCIPLES:For empiric therapy, reassess at day 4,
consult IDNarrow spectrum when bacteria identifiedConvert to oral therapy when possible
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SAVING ANTIBIOTICS SAVES SAVING ANTIBIOTICS SAVES LIVES!!!LIVES!!!
Clinical Pulmonary Infection Score (CPIS)Takes into account
temperature,wbc,secretions,ventilation,xray</- 6 ( treat with 3 days levofloxacin or
cefotaxime) >6 ( bronch and treat with 8 days
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SAVING ANTIBIOTICS SAVES SAVING ANTIBIOTICS SAVES LIVES!!!LIVES!!!
BENEFITS:Reduced use of broad spectrum agentsReduced resistanceReduced LOSReduced fungal infectionsReduced costs >$200,000
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CPIS Use for Non-invasive CPIS Use for Non-invasive Diagnosis of HAP/VAP Diagnosis of HAP/VAP
CPIS≤6CPIS≤6CPIS≤6CPIS≤6
Consider treatmentConsider treatmentConsider treatmentConsider treatment
Calculate CPISCalculate CPIS
CPIS>6CPIS>6CPIS>6CPIS>6
Gram stain of Gram stain of Tracheobronchial (TB) Tracheobronchial (TB)
secretionssecretions
Gram stain of Gram stain of Tracheobronchial (TB) Tracheobronchial (TB)
secretionssecretions
Treatment accordingTreatment according to Gram stainto Gram stain
Treatment accordingTreatment according to Gram stainto Gram stain
Recalculate CPIS daily, Recalculate CPIS daily, examine Gram stainexamine Gram stain
Recalculate CPIS daily, Recalculate CPIS daily, examine Gram stainexamine Gram stain
Pugin J. Am Rev Respir Dis. 1991;143:1121-9. Pugin J. Minerva Anestesiol. 2002;68(4):261-5.
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CPIS Antibiotic StudyCPIS Antibiotic Study
Inclusion Criteria:– Clinical Pulmonary infection score (CPIS) 6– Ventilated or non-ventilated
Exclusion Criteria:– Infected with HIV 18 years of age
Singh N, et al. Am J Respir Crit Care Med. 2000;162:505-511.
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CPIS Antibiotic Study: CPIS Antibiotic Study: Trial DesignTrial Design
CPIS≤6CPIS≤6
Standard Standard TherapyTherapy
(antibiotics for (antibiotics for 10-21 days)10-21 days)
Standard Standard TherapyTherapy
(antibiotics for (antibiotics for 10-21 days)10-21 days)
Experimental Experimental TherapyTherapy
Experimental Experimental TherapyTherapy
Ciprofloxacin for 3 daysCiprofloxacin for 3 daysCiprofloxacin for 3 daysCiprofloxacin for 3 days
CPIS >6CPIS >6CPIS >6CPIS >6
Treat as Treat as pneumoniapneumonia
Treat as Treat as pneumoniapneumonia
Singh N, et al. Am J Respir Crit Care Med. 2000;162:505-11.
CPIS ≤6CPIS ≤6CPIS ≤6CPIS ≤6
Discontinue Discontinue treatmenttreatment
Discontinue Discontinue treatmenttreatment
CPIS calculated at 3 days
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CPIS Antibiotic Study: CPIS Antibiotic Study: OutcomesOutcomes
Experimental Therapy
(n=39)
Standard Therapy (n=42)
p Value
Deaths at 3 days 0% (0/39) 7% (3/42) NS
CPIS >6 at 3 days 21% (8/39) 23% (9/39) NS
Extrapulmonary infections
18% (7/39) 15% (6/39) NS
Antibiotic continuation >3 days
28% (11/39) 97% (38/39) 0.0001
Data for patients with entry CPIS 6 subject to standard and experimental therapy
Singh N, et al. Am J Respir Crit Care Med. 2000;162:505-511.
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CPIS Antibiotic Study: CPIS Antibiotic Study: OutcomesOutcomes
Experimental Therapy
(n=39)
Standard Therapy (n=42)
p Value
Antibiotic continuation > 3 days
0% (0/25) 96% (24/25) 0.0001
Mean duration of antibiotics, day
3 9.8 0.0001
Mean cost $259 $640 0.0001
Data for patients with CPIS 6 at the 3-day evaluation point and no extrapulmonary infections
Singh N, et al. Am J Respir Crit Care Med. 2000;162:505-511.
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CPIS Antibiotic Study: CPIS Antibiotic Study: ConclusionsConclusions
Prolonged (i.e. >3 days) use of antibiotics in patients with an initial CPIS ≤6 may be unnecessary and inappropriate
Singh N, et al. Am J Respir Crit Care Med. 2000;162:505-511.
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FUNGAL INFECTIONSFUNGAL INFECTIONS
RISK FACTORSTPNSteroidsBroad spectrum antibioticsAbdominal involvementImmunosuppression
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ANTIFUNGAL AGENTSANTIFUNGAL AGENTS
Polyenes: Amphotericin B (binds to sterols and disrupts barrier resulting in leakage of intracellular contents
For hemodynamically unstable, systemic infections
Adverse effects may limit treatment
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ANTIFUNGAL AGENTS cont’dANTIFUNGAL AGENTS cont’d
Azoles: Fluconazole, voriconazole, itraconazole (inhibit p450-mediated 14-alpha demethylase in the sterol)
Good activity vs C. albicans, resistance to Krusei, Glabrata
Numerous drug interactions
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ANTIFUNGAL AGENTS cont’dANTIFUNGAL AGENTS cont’d
Echinocandins: Caspofungen (inhibit fungal cell wall synthesis)
Active against C. albicans, krusei, glabratacost