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Evaluation of Acinetobacter Infection

Sarah Nelson, Pharm.D.Pharmacy Practice Resident

Acinetobacter• Non-fermenting, non-motile, aerobic gram

negative coccobacilli

• Isolated from soil, water, animals, and humans

• Colonizes on inanimate objects with high stability

•Ventilators, mattresses, pillows, bed rails, urine collection jugs, IV equipment, nebulizers, etc.Giamarellou, H. et al. Acinetobacter baumannii: a universal threat to public health?

International Journal of Antimicrobial Agents.2008;32:106-119

Clinical Manifestations

•Pulmonary

•Bacteremia

•Skin & skin structure infections

•Urinary tract infections

•Post surgical meningitis

Giamarellou, H. et al. Acinetobacter baumannii: a universal threat to public health? International Journal of Antimicrobial Agents.2008;32:106-119

Mechanisms of Resistance

Munoz-Price, L. et al. Acinetobacter Infection. N Engl J Med. 2008;358(12):1271-81

Current Treatment Options

•Sulbactam based β-lactams

•Carbapenems

•Tigecycline

•Colistin

Background• 29 critically ill patients with pneumonia or

bacteremia causes by MDR Acinetobacter baumanii– Treatment: IV Colistin (2 million IU three times

daily) PLUS IV rifampicin (10mg/kg every 12 hours)

– Mean duration of treatment: 17.6 days (+/- 10.4)

– Clinical & microbiological response: 76% (22 pts)

– Infection-related mortality: 21% (6 pts)– Nephrotoxicity: 10% (3 pts)

Colistin and rifampicin in the treatment of multidrug-resistant Acinetobacter baumannii infections. J Antimicrob Chemother. 2008;61(2):417-420

Background

Kwon, KT et al. Impact of imipenem resistance on mortality in patients with Acinetobacter bacteremia. J antimicrob Chemother. 2007;59:525-530

• Higher 30 day mortality with:

• MDR strain of Acinetobacter caused infection (57.5% vs. 27.5%)

• Inappropriate empiric treatment was utilized (60% vs. 20%)

Objectives

• Characterize the extent of Acinetobacter infection at VCUHS

• Identify common treatment regimens currently utilized at VCUHS

• Delineate adverse effects associated with the most utilized treatment regimens

• Provide education regarding selection of treatment regimen if deemed necessary

Methods

• Retrospective– July 1, 2007- July 31, 2008

• Quality Improvement Project

• IRB Approval, expedited

Patients

• Inclusion Criteria– Adults (≥18 years of age)– ≥ 1 positive culture of Acinetobacter

calcoaceticus-baumannii complex– Received antimicrobial treatment for ≥ 2

days

• Exculsion Criteria– Infection with other species of Acinetobacter

•A. lwoffii•Undifferentiated specimens

Data Collection

• Demographics

• Specimen information•Source, sensitivities

• Antimicrobial Therapy•Empiric & final drug therapy

• Adverse Reactions•Serum Creatinine & BUN

Data Collection• Efficacy Outcomes

– Favorable vs. unfavorable response•Favorable:

– Signs & symptoms resolved within 48 hours of end of therapy

– Negative repeat culture

•Unfavorable:– Signs & symptoms persisted >48

hours after therapy ended– Required additional antibiotic therapy– Positive repeat culture

Statistical Analyses

• Descriptive statistics were used to describe variables

• Chi-squared test was used to identify significant outcomes

• Logistic regression was used to determine independent risk factors for favorable outcomes

Study Subjects

• 207 patients with ≥ 1 positive culture for Acinetobacter calcoaceticus-baumannii complex– 83 patients excluded

•Other species•<18 years old•Outpatients•23 hour observation

– 12 charts not available

• 112 patients included in study

Demographics

Overall

(n=112)Favorable

Outcome (n=76)Unfavorable

Outcome (n= 34)

Male 59 (53%) 38 (50%) 20 (59%)

Age (years) 52.6 51.4 57.1

LOS (days) 28.5 27.5 32

Days to positive culture

2.5 2.5 2.6

>1 source of Acinetobacter

22 (20%)

Source of Infection

0

10

20

30

40

50

Blood Urine Respiratory Wound Other

Locality of Infection

MRICU

Surgery/Trauma

NSICU

CTSICUBURN

General Medicine

SurgeryOncology

OrthoRehab Other

0

5

10

15

20

25

30MRICU BURN Ortho

Rates of ResistanceAntimicrobial 2007

AntibiogramStudy Group

Amikacin --- 72%

Cefepime 60% 74%

Ciprofloxacin 65% 76%

Gentamicin 58% 68%

Imipenem 31% 56%

TMP/SMX 50% 64%

Piperacillin/Tazobactam

48% 70%

Tigecycline --- 31%

Colistin --- 0%

Empiric Therapy• Appropriate empiric therapy is associated with a

favorable outcome (p<0.0001)

• 29 patients (26%) were treated with appropriate empiric therapy– 28 (97%) had a favorable outcome

• Inappropriate empiric therapy accounts for 33 of the 34 unfavorable outcomes (97%)

• 17% of patients were not started on empiric antimicrobial therapy

Tailored Antimicrobial Therapy

• Appropriate tailored therapy is associated with a favorable outcome (p<0.0001)

• 79 (72%) patients were treated with appropriate antimicrobial therapy– 65 (82%) patients had a favorable outcome

• Average duration of tailored antimicrobial therapy was 12.4 days

• Most common final antimicrobial therapy included imipenem (18), colistin (17), tigecycline (12), & piperacillin/tazobactam (10)– 14 patients were treated with combination therapy

Colistin

• 17 patients were treated with colistin– Never used as empiric therapy– Used as monotherapy in 9 (53%) patients– Most commonly used with tigecycline for

combination therapy

• Intravenous route most common; inhalation also utilized for respiratory infections

• 3 (18%) patients experienced an increase in serum creatinine & 4 (25%) patients experienced an increase in BUN

Limitations

• Retrospective analysis– Documentation of assessment and plan

• Evaluation of only Acinetobacter calcoaceticus-baumannii complex

• Withdrawl of care promoted an unfavorable endpoint

Conclusion

• Selection of correct empiric antimicrobial therapy is necessary for a favorable outcome

• No independent risk factors exist that demonstrate a favorable outcome

• Nosocomial strains of Acinetobacter calcoaceticus-baumannii complex exhibit increased resistance to common antimicrobials

• Colistin is an effective and safe antimicrobial with 100% susceptibility to the MDR Acinetobacter baumanii-calcoaceticus complex