Drug Treatment for Multidrug-resistant Acinetobacter baumannii Infections

Matteo Bassetti; Elda Righi; Silvano Esposito; Nicola Petrosillo; Laura Nicolini

Future Microbiol. 2008;3(6):649-660.

Abstract and Introduction

Acinetobacter baumannii has emerged in the last decades as a major cause of healthcare-associated infections and nosocomial outbreaks. Multidrug-resistant (MDR) A. baumannii is a rapidly emerging pathogen in healthcare settings, where it causes infections that include bacteremia, pneumonia, meningitis, and urinary tract and wound infections. Antimicrobial resistance poses great limits for therapeutic options in infected patients, especially if the isolates are resistant to the carbapenems. Other therapeutic options include sulbactam, aminoglycosides, polymixyns and tigecycline. The discovery of new therapies coupled with the development of controlled clinical trial antibiotic testing combinations and the prevention of transmission of MDR Acinetobacter infection are essential to face this important hospital problem.

Acinetobacter baumannii is a ubiquitous pathogen that has emerged in the last few decades as a major cause of healthcare-associated infections (HAIs) and nosocomial outbreaks.^[1]A. baumannii's capability to replicate in the hospital environment is facilitated both by tolerance to desiccation and multidrug resistance, the latter also favoring endemic infections through antibiotic-selective pressure.^[2] Multidrug-resistant (MDR) A. baumannii is a rapidly emerging pathogen in the healthcare setting, where it causes infections that include bacteremia, pneumonia, meningitis, urinary tract infection and wound infection. Antimicrobial resistance poses great limits for therapeutic options in infected patients, especially if the isolates are resistant to carbapenems. Other therapeutic options include ß-lactamase inhibitors, aminoglycosides, polymixyn and tigecycline.^[3] The discovery of new therapies coupled with the development of controlled clinical trials on antibiotics combinations and the prevention of the transmission of MDR Acinetobacter infection are essential to face this important hospital problem. The epidemiology and the risk factors related to MDR A. baumannii infections, as well as the currently therapeutic options are revised in this article.

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Cite this: Drug Treatment for Multidrug-resistant Acinetobacter baumannii Infections - Medscape - Dec 01, 2008.

Abstract and Introduction
Epidemiology & Risk Factors Associated with A. baumannii Infections
Acinetobacter spp. Infections & Multidrug Resistance
Therapy
Future Perspective
References
Sidebar: Executive Summary

Risk Factors Associated with Outbreaks of Multidrug-resistant *Acinetobacter baumannii* Worldwide
Setting	Risk factors	Intervention	Ref.
Tertiary care (Turkey 2004) n = 66	Duration of hospital stay Previous antibiotic use ICU stay	n.d.	12
Surgical ICU (Greece 2003-2005) n = 52	Previous septic shock Previous ARDS Previous antibiotics use Previous aminoglycoside use Reoperation	n.d.	109
Tertiary care (Thailand 2003-2005) n = 899 (included colonizations)	Admission to ICU/RCU Use of antibiotics Previous use of imipenem	n.d.	120
ICU (USA 2004-2005) n = 67	High APACHE II Duration of incubation Exposure to bronchoscopy COPD Fluconazole and levofloxacin	Removal of items with upholstered surfaces Implementation of contact isolation (patients with suspected infection)	121
Neonatal ICU (Taiwan 2000-2005) n = 2 (two of nine colonization)	Ventilation tube Healthcare workers' hands	Re-inforcement of handwashing procedures Adherence to intervention detected	122
Tertiary care hospital (USA 2003) n = 11	Pulsatile lavage treatment for wound debridment	Infection control precautions during pulsatile lavage therapy Labeling included in pulsatile lavage equipment	123
Neonatal ICU (Brazil 2001-2002) n = 11	Exposure to antibiotics Invasive devices Birth weight < 1500 g Age ≤ 7 days Hospitalization ≥ 7 days Exposure to carbapenem Mechanical ventilation	Not indicated (possible source of transmission from another hospital)	124
Tertiary hospital (Spain 1997-1998) n = 153 isolates	Previous carriage of carbapenem-resistant A. baumannii Previous carbapenems Admission into a ward with a high density of patients infected with carbapenem-resistant A. baumannii	Restricted carbapenem use Closure of all ICUs for decontamination Strict compliance with cross-transmission Prevention protocols	125
Nursery (Bahamas 1998) n = 8	Air conditioners Intravenous catheters	Infection control of intravenous catheters Changing air conditioning	126

APACHE: Acute Physiological and Chronic Health Evaluation; ARDS: Acute respiratory distress syndrome; COPD: Chronic obstructive pulmonary disease; ICU:Intensive care unit ; n.d.: Not determined; RCU: Respiratory care unit.

Recent *Acinetobacter baumannii* Outbreaks and Associated Resistances
Setting	Year	Susceptibility	Ref.
Tertiary hospital (Korea) n=53	2004	Imipenem (44/53), ampicillin/sulbactam (51/53), gentamycin (41/53)	16
Academic hospital (USA) n = 129 (isolates)	2006	Carbapenems, gentamicin (52/129)	81
ICU (USA) n = 67	2004-2005	Carbapenems, variably aminoglycosides	121
County hospitals (USA) n = 20	2005-2006	Tigecycline, tetracycline	127
ICU (Greece) n = 15	2002	Colistin	128
Tertiary care hospital (Italy) n = 38	2003-2004	Colistin	129
Burn unit (France) n = 6	2003-2004	Rifampin and colistin	130
ICU (Turkey)	2006	Colistin and tigecycline	131
Burn ICU (USA) n = 30	2004-2005	Colisitn	132

ICU: Intensive care unit.

Multidrug-resistant *Acinetobacter baumannii* Infection Monotherapy and Efficacy Reported
Drug	Setting	Toxicity	Efficacy	Development of resistance	Ref.
Sulbactam	VAP, n = 13 VAP, n = 14 Various, n = 40	Renal (15.3%) No major a.e. No major a.e.	61.5% clinical 64.3% clinical 67.5% clinical	n.d. n.d. n.d.	133 134 135
Carbapenems	VAP, n = 63 VAP, n = 14	n.d. Six of 14 renal failure	56% clinical 57% clinical	One rebound treated with ampicillin/sulbactam n.d.	65 77
Colistin	VAP, n = 15 Various, n = 12 Various, n = 30 Various, n = 71 VAP, n = 31	Renal (33%) Renal (2/27) Renal 10.9% Renal 30.8% No acute renal failure	60% clinical 85% clinical 71.7% clinical 80.8% clinical 75% clinical	n.d. n.d. n.d. n.d. n.d.	132 136 79 137 138
Tigecycline	VAP and sepsis, n = 25 HAP and sepsis, n = 42	No documented a.e. No documented a.e.	84% clinical 76% clinical	Two resistance, one patient with two recurrences and increased MIC Three resistance	106 107

a.e.: Adverse effects; HAP: Hospital-acquired pneumonia; MIC: Minimum inhibitory concentration; n.d: Not determined; VAP: Ventilator-associated pneumonia.

Multidrug-resistant *Acinetobacter baumannii* Infection Monotherapy and Efficacy Reported
Drug	Setting	Toxicity	Efficacy	Development of resistance	Ref.
Sulbactam	VAP, n = 13 VAP, n = 14 Various, n = 40	Renal (15.3%) No major a.e. No major a.e.	61.5% clinical 64.3% clinical 67.5% clinical	n.d. n.d. n.d.	133 134 135
Carbapenems	VAP, n = 63 VAP, n = 14	n.d. Six of 14 renal failure	56% clinical 57% clinical	One rebound treated with ampicillin/sulbactam n.d.	65 77
Colistin	VAP, n = 15 Various, n = 12 Various, n = 30 Various, n = 71 VAP, n = 31	Renal (33%) Renal (2/27) Renal 10.9% Renal 30.8% No acute renal failure	60% clinical 85% clinical 71.7% clinical 80.8% clinical 75% clinical	n.d. n.d. n.d. n.d. n.d.	132 136 79 137 138
Tigecycline	VAP and sepsis, n = 25 HAP and sepsis, n = 42	No documented a.e. No documented a.e.	84% clinical 76% clinical	Two resistance, one patient with two recurrences and increased MIC Three resistance	106 107

a.e.: Adverse effects; HAP: Hospital-acquired pneumonia; MIC: Minimum inhibitory concentration; n.d: Not determined; VAP: Ventilator-associated pneumonia.

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Drug Treatment for Multidrug-resistant Acinetobacter baumannii Infections

Abstract and Introduction

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Sidebar: Executive Summary

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