antimicrobial agents for intra-abdominal infections ·...

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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