antimicrobial agents for intra-abdominal infections ·...
TRANSCRIPT
Surgical infection
ผ.ศ. น.พ. ก ำธร มำลำธรรมหน่วยโรคติดเชื้อ ภำควชิำอำยุรศำสตร์
คณะแพทยศำสตร์ โรงพยำบำลรำมำธบิดี
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Scope
Surgical prophylaxis: Pharmacologic
approach to prevent SSI
Antimicrobial therapy for surgical
infections
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Surgical prophylaxis
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Principles of Antimicrobial Prophylaxis
Use an AMP agent for all operations
or classes of operations in which its
use has been shown to reduce SSI
rates based on evidence from clinical
trials or for those operations after
which incisional or organ/space SSI
would represent a catastrophe.
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Principles of Antimicrobial Prophylaxis
Use an AMP agent that is safe,
inexpensive, and bactericidal with an
in vitro spectrum that covers the most
probable intra-operative
contaminants for the operation.
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Principles of Antimicrobial Prophylaxis
Time the infusion of the initial dose of
antimicrobial agent so that a
bactericidal concentration of the drug
is established in serum and tissues
by the time the skin is incised.
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Principles of Antimicrobial Prophylaxis
Maintain therapeutic levels of the
antimicrobial agent in both serum
and tissues throughout the operation
and until, at most, a few hours after
the incision is closed in the operating
room.
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Choice of antimicrobial agents
Cefazolin: most surgery
AMC, AMS, cefoxitin: GI and
urogenital tract
Cefuroxime: GI and urogenital tract
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Modification of Antimicrobial
Prophylaxis Based on Rectal Culture
to Prevent Fluoroquinolone-
Resistant Escherichia coli Infections
after Prostate Biopsy
Suwantarat N et al Infect Control Hosp Epidemiol 2013;34(9):973-976 9
Suwantarat N et al Infect Control Hosp Epidemiol 2013;34(9):973-976 10
Effect of Preoperative Antibiotic
Prophylaxis on Surgical Site Infections
Complicating Cardiac Surgery
Finkelstein R et al Infect Control Hosp Epidemiol 2014;35(1):69-74 11
Results
2,637 patients
Overall SSI rate was 8.4%.
Superficial and deep/organ space
infection rates were 7.9% vs 10.0%;
4.7% vs 6.8%; and 3.3% vs 3.3%,
respectively for patients receiving
cefazolin or vancomycin.
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Suppurative thrombophlebitis
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Factors to consider in intra-abdominal
infection
Primary & secondary peritonitis
–Community-type organism
–Unusual presentation, e.g. TB
Tertiary peritonitis
–Nosocomial pathogens: MRSA, MDR A. baumannii, P. aeruginosa
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Antimicrobial agents for intra-
abdominal infection
Ceftriaxone + metronidazole
– Lowest cot, convenience
– Lac coverage for enterococci
Ampicillin/sulbactam or
amoxicillin/clavulanate
aminoglycoside
Others:
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Acute necrotizing pancreatitis
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Etiologic agents: pancreatic
abscess
Gram-negative enteric bacilli
– E. coli, Klebsiella spp., Enterobacteriaceae
Anaerobes
– Anaerobic GPC, Bacteroides spp.,
Actinomyces spp.
Gram-positive cocci
– Streptococci, Staphylococci, Enterococci
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Antibiotic prophylaxis in acute
necrotizing pancreatitis
Lack of consistent benefit
Variable inclusion criteria &
methodological quality
Different regimens
Potential for harm
Change pancreatic isolates (Gram-ve to
fungi and Gram+ve organisms)
Nathens AB., et al Crit Care Med 2004; 32:2524 –2536) 18
No reduction in mortality (RR, .76;
95% CI, .49 –1.16)
No protection against infected
necrosis (RR, .79; 95% CI, .56–1.11)
or surgical intervention (RR, .88; 95%
CI, .65–1.20).
Jafri NS. et al. The American Journal of Surgery (2009) 197, 806-813
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Post-operative infections
Surgical site
Tracheobronchitis/Pneumonia: A. baumannii
Urinary tract infection: E. coli
Catheter-associated infection
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Post-operative fever
Atelectasis
Blood transfusion
Phlebitis
–Chemical
– Infectious
Pseudogout/gout
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Ramabio: Antibiogram in your
hand
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Ramabio: Antibiogram in your hand
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Ramabio: Antibiogram in your hand
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Risk factors for MDR
Previous hospitalization in the past 3
months
History of exposure to antibiotics
Indwelling medical devices
ICU or other areas with high incidence of
MDR stay
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Susceptibility of E. coli
30
40
50
60
70
80
90
100
98 99 00 01 02 03 04 05 06 07 08 09 10 11
AMOX/CLAV CFR CRO CAZ NFX AMK GEN TMP/SMX
National Antimicrobial Resistance Surveillance Center, Thailand26
Susceptibility of P. aeruginosa
60
65
70
75
80
85
90
98 99 00 01 02 03 04 05 06 07 08 09 10 11
CAZ Cefepime IMP PIP CPX AMK GEN
National Antimicrobial Resistance Surveillance Center, Thailand27
Susceptibility of A. baumannii
0
20
40
60
80
100
98 99 00 01 02 03 04 05 06 07 08 09 10 11
CPZ/SUL
IMP
National Antimicrobial Resistance Surveillance Center, Thailand28
Available antimicrobial agents
Beta-lactam
– Penicillin: Amp/sulb, Amox/clav, Pip/tazo
– Cephalosporins: cefoxitin, ceftriaxone, ceftazidime,
cefoperazone/sulbactam, cefepime, cefpirome
– Carbapenems: imipenem, meropenem, doripenem
ertapenem
Fluoroquinolones: ciprofloxacin, ofloxacin,
levofloxacin, moxifloxacin
Aminoglycosides: amikacin, gentamicin
Miscellaneous: metronidazole, clindamycin
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b-lactam/b-lactamase inhibitor
Ampicillin/sulbactam
Amoxycillin/clavulanate
Piperacillin/tazobactam
Cefoperazone/sulbactam
Better anti gram –ve and anaerobic bacteria except P. aeruginosa
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Classification of Carbapenems
GROUP 1Carbapenems
(community
acquired
infections)
GROUP 2Carbapenems
(hospital acquired
infections –Pseudomonas and
Acinetobacter activity)
GROUP 3Carbapenems
(hospital acquired
infections –Pseudomonas and
MRSA activity)
Ertapenem Imipenem
Meropenem
Panipenem
Biapenem
Doripenem
CS-023
(investigational)
Shah PM and Isaacs RD. J Antimicrob Chemother 2003; 52:538-42.
Not allcarbapenems are the same
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Comparison of Carbapenems
Nicolau DP. Pharmacochemother 2008;9:23-37. 32
In vitro activities of carbapenems
Organism
MIC (mg/ml)
Meropenem Imipenem Ertapenem
S. aureus 0.25 0.06 0.25–0.5
S. pneumoniae PS 0.25 0.06 0.03
S. pneumoniae PR 1 0.5 1.0–2
S. pyogenes <0.06 <0.06 0.016–0.06
E. faecalis 8 2 16
Norrby SR Infect Dis Clin Practice 1997;6 : 291 – 30333
Imipenem/cilastatin
Warnings and Precautions
Seizures
– Patients at risk: Pre-existing CNS disorders
Impaired renal function
Hemodialysis patients
Low body weight
Drug Interactions
– Ganciclovir (increased seizures)
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Meta-analysisClinical Response in Severe Infections
Meropenem vs. Imipenem
Edwards SJ et al. Curr Med Res Opin 2005;21:785-94.
Favors meropenemImipenem35
Ertapenem Pharmacokinetics Absorption: IM bioavailability = 90%; Cmax ~ 2.3h
Distribution:– Serum concentrations
1G IV: 155 ug/mL @ 0.5h
1G IM: 67 ug/mL @ 2 h
– Non-linear PK due to concentration-dependent protein binding 95% protein bound at conc < 100 ug/mL
85% protein bound at conc ~ 300 ug/mL
Metabolism: hydrolysis of beta-lactam ring
Elimination: – t 1/2 = 4 hours in adults and peds > 12 yo
– t 1/2 = 2.5 hours in peds 3 months - 12 years old
– 80% excreted in urine, 10% in feces36
Ertapenem Dosing and Administration
Usual dosing:– Adults and peds > 12 yo: 1G IM/IV qd
– < 3 months - 12 years: 15 mg/kg IM/IV BID (not to exceed 1G/d)
Dosage adjustment in renal dysfunction (adults):– Clcr </= 30 ml/min or ESRD: 500 mg IM/IV qd
– HD: if dose given < 6 hours prior to HD, give 125mg supplemental dose following HD.
There is no data in pediatric patients with renal dysfunction
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Das I et al J Hosp Infect 2002; 50:110-114 39
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Ceftazidime & Cefepime
Ceftazidime
– Anti-pseudomonal 3rd generation
cephalosporin, no anti-staph activity
Cefepime
– 4th generation cephalosporin
– Anti-pseudomonal
– Anti-staph
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Piperacillin/tazobactam
Activity against – gram-positive species (streptococcus)
– Neisseria
– Haemophilus
– Enterobacteriaceae spp.
– Anaerobes
Acts synergistically against Pseudomonas and some Enterobactericeae species when it is combined with an aminoglycoside
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Cefoperazone-sulbactam
Enhanced potency against Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis
Another third generation cephalosporin
with modest activity against P. aeruginosa
Used to treat intra-abdominal, biliary and
gynecologic infections
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Cefoperazone-sulbactam
Usual Adult Dose
– Mild-moderately severe 1 –2 g q12h
– Severe Disease 2 – 4 g q8h
Peak serum concentration (1g): 153ug/mL
t 1/2: 1.6 - 2.1 hrs
Serum protein binding: 90%
Route of excretion : hepatic 80%; renal 20%
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Fluoroquinolones
Ciprofloxacin: +ve anti-pseudomonal
activity
Ofloxacin, levofloxacin
Moxifloxacin (some anti-
anaerobic/Gm +ve bacteria)
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Effective use of antimicrobial agents
Ascertain the diagnosis
– Lower resp. tract infection:
Symptoms and signs: O2 requirement,
amount and character of resp. secretion,
VS, breath sound
Lab: CXR, Gram stain and culture
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Effective use of antimicrobial agents
Ascertain the diagnosis
– Surgical site infection
Symptoms and signs: vital signs, inflamed
site, purulent drainage
Lab: Gram stain and culture
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Effective use of antimicrobial agents
Ascertain the diagnosis
–UTI
Symptoms and signs: vital signs
Lab: Urinalysis, culture
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Effective use of antimicrobial agents
Ascertain the diagnosis
– Bloodstream infection
Symptoms and signs: vital signs
Lab: blood culture
– Paired simultaneous peripheral and central
venous blood
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Thank you for your attention
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