ICU related bacterial ICU related bacterial infectioninfection

Janet Lee, Pharmacist, Janet Lee, Pharmacist, KWHKWH

ContentContent

• Bacterial infection in ICU • Why is it different ??• Treatment: Antibiotic• An impressive Case • Personal sharing• Conclusion

Bacterial infection in ICUBacterial infection in ICU

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Clin Infect Dis 1997;24:211-215Seminars in Respiratory and critical care med2003,24(1):3-22,

Though ICUs account for only 8% of hospital beds, 45% of infections in a hospital originate in an ICU

Distribution of major sites of Distribution of major sites of infection in medical ICUinfection in medical ICU’’ss

5%5%

6%

30%

30%

16%

3% 3%

CVS GI LRI PN UTI BSI SST EENT

Ref. : Seminars in Respiratory and critical care med 24(1):3-22,2003

Bacteria infection is common in Bacteria infection is common in ICUICU

• Seriously compromised or critically ill patients

• Invasive diagnostic or therapeutic procedures

Bacteria infection is common in Bacteria infection is common in ICUICU

• Patients at the extremes of ages• Most crowded place• Prolong hospitalization• Others: e.g multiple

sites of injury

Common infection in ICUCommon infection in ICU

• Low respiratory tract infection

• Urinary tract infection

• Primary bacteremia– Catheter-related infection

• Surgical wound infection

• Gastrointestinal tract infection

Why the infection is Different in ICU?

Multiple mechanism of infection

Pt usually cannot communicate

Inflammation mimics

infection

Why the infection is Different in ICU?

Skin integrity – operations, wounds, ulcers, poor perfusion, central lines, drains, tubes, catheters, stomas……

Immunosuppression and immunoparesis

TreatmentTreatment• Surgery:

• Get the pus out! All of it!

• Drug Tx: Antibiotics, Anti-fungal….– Empirical Tx– Base on microbiology results– Points to be considered:

• Pharmacokinetic• Pharmacodynamic• Side effect monitoring• duration• Resistance pattern

THE EARLIEST , THE BETTERTHE EARLIEST , THE BETTERTHE EARLIEST , THE BETTER

Empirical TreatmentEmpirical Treatment• Diagnosis

• Sources of infection

• Know your Local Pathogens

• Follow local and international guidelines

• Patient allergy record

Early VAP Late VAPAmp/sulb, ceftriaxone, ertapenem, or moxifloxacin (PCN all)

Imipenem or mero + vancomycin +/-aminoglycoside or ciprofloxacin

Standard duration of therapy 8 days except for Pseudomonas

De-escalation based on quantitative culture Consider linezolid for documented MRSA pneumonia

If GPC in clusters on gram stain, history of MRSA, or RF for MRSA, add vancomycin

Empiric to Specific Therapy in Empiric to Specific Therapy in VAPVAP

PharmacokineticsPharmacokinetics

• Renal adjustment following CrCl– CrCl = [(140 - age) x IBW] / (Scr x 72)

(x 0.85 for females)• Dose adjustment for hemodialysis

• Dose adjustment for other disease state, e.g. liver failure

• Obesity

Antibiotic PharmacodynamicsAntibiotic Pharmacodynamics

rate and extent of an antibiotic’s activity depend on:-drug concentrations at the site of infection,-bacterial load-phase of bacterial growth-MIC of the pathogen

PseudomonasPseudomonas and Fluoroquinolonesand Fluoroquinolones

Drug Dose Cmax MIC AUCfree:MICCiprofloxacin 400 q12 4.1 0.125 144

400 q8 4.1 0.125 184Levofloxacin 750 q24 12.1 0.5 152Gatifloxacin 400 q12 4.6 1.0 28Moxifloxacin 400 q24 4.2 2.0 10

New IDSA and ATS Guidelines recommend Ciprofloxacin 400mg IV q8hr or Levofloxacin 750 mg qdAm J Respir Crit Care med 2005;171:388-416

HighHigh--dose, Shortdose, Short--course course Levofloxacin forLevofloxacin for CAPCAP

• Attempt to increase AUC:MIC ratio while decreasing overall drug exposure

• Multi-center, randomized, double-blind study comparing 750 mg qd x 5 days vs. 500 mg qd x 10 days in the treatment of CAP

• Found equivalent clinical and microbiological outcomes

Clin Infect Dis 2003;37:752-60

Adverse effects MonitoringAdverse effects Monitoring

• A/E: e.g: Red man syndrome

• Ototoxicity and nephrotoxicity in aminoglycosides

• Cephalosporin associated with seizure

Duration of treatmentDuration of treatment

• In UK ICU median duration of antibiotic therapy is 6 days

• Range 0 to 29 days!!!!• Similar for both community and

nosocomial acquired infections. Anaesthesia. 2004 Sep;59(9):885-90.

Anaesthesia. 2004 Sep;59(9):885-90.

Duration of Therapy for VAPDuration of Therapy for VAP

Variable 8 Days (n=197) 15 Days (n=204)Mortality 18.8% 17.2%Recurrent infection 28.9% 26%Antibiotic free days 13.1 days 8.7 daysAntimicrobial resistance 42.1% 62.0%

Recurrence rate amongNon-lactose fermenters 40.6% 25.4%

JAMA 2003;290:2588-2598

Resistant StrainsRare

xx

Resistant Strains Dominant

Antimicrobial Exposure

xxxx

xx

xx

xx

Antimicrobial resistanceAntimicrobial resistance

Acinetobacter bacteremiaAcinetobacter bacteremia

Eur J Clin Microbiol Infect Dis. 27:607-612, 2008.

Colistin/Polymixin EColistin/Polymixin E

• Cationic polypeptide• Detergent-like disruption of outer

cytoplasmic membrane of Gram-negative bacteria

• Used in treatment of highly resistant Acinetobacter and Pseudomonas when no other options

• Can accumulate in tissues and continue to be released after discontinuing therapy

• Nephrotoxicity (20-30%), neurotoxicity (7%)

A CaseA Case• 55yr old male• SH: retiree• CC:• Patient was admitted for pneumonia with

prostrating high fever and arthralgia . He complained of headache and stiff neck when admitted, and therefore LP was ordered. However, it showed normal results.

• Allergic Hx: Penicillin

• Vital signs• Temp 39• RR 24 WBC 1300

A CaseA Case

• Day 1• Fever persists, WBC 13000• He presented as bacterial pneumonia.• Chest X ray shows patchy infiltrates• Amox/ clav was started due to empirical

choice, changed to Levofloxacin 500mg daily due to his allergy history

A CaseA Case

Day 3• Culture negative, no improvement• Step up to piperacillin/tazobactamDay 4, Day 5, Day 6 ???????????• Fever persists• He developed into severe pneumonia • X-ray showed increased infiltrates

A CaseA Case

• Day 8• Meet with relative , collected a history of

patient in contact with parrot before admission

• May be source of infection• Started doxycycline 100mg bd• Found culture of Chlamydia psittaci

Personal SharingPersonal Sharing

• Multidisciplinary approach– Nurses– Doctors– Physiotherapist– Pharmacist– Microbiologist

• Infection control

Infection control measures in ICUInfection control measures in ICU

• Eliminate risk factors when possible• Extubate• Remove NG tube• Care of catheter sites• Proper respiratory care

• Selective decontamination (Controversial measure)

• Control antibiotic use• Treatment of underlying diseases

ConclusionConclusion

• Infectious disease is common in ICU• Drug treatment remains the mainstay of

therapy• Proper use is of utmost importance• Multidisciplinary approach proves its

effectiveness in critical care• Pharmacist may take up a role

ReferencesReferences• Richards, M.; Thursky, K; Buising, K. Epidemiology, Prevalence, and Sites of Infections in Intensive Care Units.

Seminars in Respiratory and critical care med 24(1):3-22,2003.• Soubrier, L. Hospital-acquired pneumonia: risk factors, clinical features, management, and antibiotic resistance.

Current Opinion in Pulmonary Medicine. 10(3):171-5, 2004.• Ibrahim EH. Sherman G. Ward S. Fraser VJ. Kollef MH. The influence of inadequate antimicrobial treatment of

bloodstream infections on patient outcomes in the ICU setting. Chest. 118(1):146-55, 2000.• Woodhead M; Welch CA; Harrison DA, et al. Community-acquired pneumonia on the intensive care unit:

secondary analysis of 17,869 cases in the ICNARC Case Critical Care (London, England). 10 Suppl 2:S1, 2006. • Cuthbertson, B; Thompson, M; Sherry, A. Antibiotic-treated infections in intensive care patients in the UK.

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Clin Infect Dis.37:1210-5, 2003.• Dunbar, LM; Wunderink, RG; Habib, MP, et al. High-Dose, Short-Course Levofloxacin for Community-Acquired

Pneumonia:A New Treatment Paradigm. Clin Infect Dis. 37:752-60, 2003• Chastre J; Wolff M; Fagon JY, et al. Comparison of 8 vs 15 Days of Antibiotic Therapy for Ventilator-Associated

Pneumonia in Adults. JAMA. 290:2588-2598, 2003• Manikal V; Landman D; Saurina G, et al. Endemic Carbapenem-resistant Acinetobacter species in Brooklyn, New

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• Wareham D; Bean DC; Khanna P, et al. Bloodstream infection due to Acinetobacter spp: epidemiology, risk factors and impact of multi-drug resistance. Eur J Clin Microbiol Infect Dis (2008) 27:607–612.

ReferencesReferences• Lowy FD. Staphylococcus aureus infections. N Engl J Med. 339:520-532, 1998• Cuthbertson BH; Thompson M; Sherry A, et al. Antibiotic-treated infections in intensive care patients in the UK

Anaesthesia. 59(9):885-90, 2004. • Papazian L, Bregeon F, Thirion X, et al. Effect of ventilator-associated pneumonia on mortality and morbidity. Am.

J. Respir. Crit. Care Med. 154: 91-97, 1996• Kollef MH. Ventilator-associated pneumonia: A multivariate analysis JAMA. 270(16), 1965-

1970,1993.• Morehead RS, Pinto SJ. Ventilator-Associated Pneumonia. Arch Intern Med. 160: 1926 – 1936, 2000 • Kollef MH; Sherman G; Ward S, et al. Inadequate antimicrobial treatment of infections: A risk factor for hospital

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Methicillin Resistance among Patients with Staphylococcus aureus Surgical Site Infection Clin Infect Dis 36:592-598, 2003.

• Cosgrove,SE, Sakoulas, G, Perencevich,EN, et al. Comparison of Mortality Associated with Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Meta-analysis. Clin Infect Dis. 36:53-9, 2003.

• Chaix, C; Durand-Zaleski, I; Alberti, C, et al. Control of Endemic Methicillin-Resistant Staphylococcus aureus. A Cost-Benefit Analysis in an Intensive Care Unit. JAMA. 282:1745-1751, 1999.

• Wilson, SJ; Knipe, CJ; Zieger, MJ, et al. Direct costs of multidrug-resistant Acinetobacter baumannii in the burn unit of a public teaching hospital. American Journal of Infection Control, 32: 342-344, 2004

• American Thoracic Society, Infectious Diseases Society of America. Guidelines for the Management of Adults with Hospital-acquired, Ventilator-associated, and Healthcare-associated Pneumonia Am J Respir Crit Care med 2005;171:388-416

• Appelbaum, PC. Resistance among Streptococcus pneumoniae: Implications for Drug Selection. Clin Infect Dis. 34:1613-20, 2002.

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