The Topic of This Month Vol. 31, No. 7 (No. 365)

Multi-drug resistant Acinetobacter
(IASR 31: 192-193, July 2010)

Acinetobacter is a genus of bacteria, which are ubiquitous in environment; they are isolated easily from soil, river water (see p. 194 of this issue).  Being non-invasive and producing no exotoxin or other pathogenic factors, Acinetobacter is non-pathogenic to healthy humans.  However, as in the case of other Gram-negative bacteria like Pseudomonas aeruginosa , once it enters the blood stream, its endotoxin (lipopolysaccharide) causes endotoxin shock and/or multiple organ failure, which is often fatal.

Acinetobacter species belong to an aerobic glucose-non-fermenting Gram-negative rod, but A. baumannii can resolve glucose by oxidation under aerobic condition, and this character is different from other Acinetobacter species.

Nosocomial infections : Since late 1980's, A. baumannii has increasingly been noted as an agent causing nosocomial infections in hospitals and other medical facilities, particularly causing ventilator associated pneumonia (VAP) in intensive care units (ICU).  Genomic species 3 and 13TU which are close to A. baumannii cause nosocomial infection less frequently than A. baumannii .

Emergence of multi-drug resistant strains: Since 1990's, multi-drug resistant A. baumannii showing resistance to fluoroquinolone, wide-spectrum cephalosporin, imipenem, amoxicillin-clavulanic acid, aminoglycoside, etc. has increasingly been isolated from clinical specimens in Germany, USA or other countries, and has become a serious clinical concern.  Since 2002 when many US soldiers wounded in Iraq War contracted such strains and died of the infection, the multi-drug resistant A. baumannii has become a general concern.

Highly aminoglycoside-resistant strains are increased in China, USA and other countries and we should watch their spreading from now on.

Incidence of multi-drug resistant Acinetobacter abroad: In USA, ventilator-associated multi-drug resistant Acinetobacter pneumoniae has tended to increase rapidly since 1990's.  It is suggested that most of the causing strains are genetically homologous or closely related to clones which spread in Europe (see p. 194 of this issue).  Not only Europe where initially multi-drug resistant A. baumannii become problem, but also China, Korea and Southeast Asian countries have reported detection of multi-drug resistant A. baumannii and outbreaks of its infection (see p. 196 of this issue).

Incidence of multi-drug resistant Acinetobacter in Japan: Compared with the high incidence abroad (see p.194&196 of this issue), the incidence of multi-drug resistant Acinetobacter is still low.  However, imported cases of multi-drug resistant Acinetobacter infections have been reported in 2008 (see p.197 of this issue), 2009 (see p.199 of this issue) and 2010 (see p.200 of this issue), and one case actually led to an outbreak of hospital infection involving 26 patients in ICU.

Japan Nosocomial Infection System (JANIS; Ministry of Health, Labour and Welfare) started in July 2000.  The laboratory section of JANIS, using the data obtained from July 2007 to December 2009, analyzed detection of Acinetobacter (A. baumannii , A. calcoaceticus , A. lwoffii , and Acientobacter sp.), and prevalence of multi-drug resistant Acinetobacter (Table 1).  The total number of bacterial isolations reported from the designated medical facilities from July 2007 to December 2009 was 3,218,820, 2.2% of which were Acinetobacter .  Sixty percent of Acinetobacter were A. baumannii .  The percentage of multi-drug resistant strain among all the Acinetobacter isolates was 0.14% (98/71,657) and about half of them were A. baumannii .  Ninety percent of the isolated multi-drug resistant Acinetobacter were derived from hospitalized patients (see p.201 of this issue).

Molecular epidemiology of multi-drug resistant strains: Since 1980's, A. baumannii has been typed according to biotype and/or genetic type.  Since early 2000's, the multi-drug resistant A. baumannii strains currently circulating in Europe have been analyzed by amplified fragment length polymorphism (AFLP), which identified presence of special clones called “pan-European clones” prone to spread in the community (European clones I-III, so far).  More recently, multi-locus sequence typing (MLST) that utilizes the polymorphism of a set of seven house keeping genes such as (gltA , gyrB , gdhB , recA , cpn60 , gpi , rpoD ) or (cpn60 , fusA , gltA , pyrG , recA , rplB , rpoB ) has been introduced (Table 2).  Strains currently spreading to the world are European clone II, which are, according to MLST typing, ST92 (identified as ST22 previously) and related strains, collectively called clonal complex 92 (CC92).  These strains have been already detected not only in Europe but also in China and other Asian countries (see p.196 of this issue).  In recent years, strains that belong to CC92 have been found in Japan.

Treatment of multi-drug resistant Acinetobacter infection: Multi-drug resistant Acinetobacter strains that produce OXA-type β-lactamase are resistant to nearly all of the antibiotics approved by health insurance coverage for treatment of infection with Gram-negative bacilli in Japan.  Therefore, for severe cases that require chemotherapy, the doctors have to import antibiotics unapproved in Japan, such as, injectable colistin, Polymyxin B, etc (see p. 194 of this issue), from abroad in his/her private capacity.  However, strains resistant to these drugs are already isolated at high frequency in Korea and other neighboring countries.  In some case, arbekacin that is used for MRSA is used to treat the multi-drug resistant Acinetobacter cases (see p. 200 of this issue).  However, arbekacin is not effective to the strains that produce ArmA (see p. 199 of this issue). 

Conclusion: Multi-drug resistant Acinetobacter is still low in prevalence in Japan.  However, as illustrated by the imported case that caused hospital infection outbreak, and in view of globally spreading multi-drug resistant Acinetobacter , medical facilities in Japan are under threat.  The role of nosocominal infection surveillance, JANIS, will become ever more important.

Hospital infection prevention measures undertaken at the level of individual hospitals and at the level of communities or as a nation should be intensified, particularly because the control of Acinetobacter is extremely difficult on account of long survival in the environment, such as clothing, bedclothes, ventilators, sinks, doorknobs, etc.

A. baumannii and A. calcoaceticus are genetically close to each other, and in the routine laboratory practice these bacteria are identified as A. calcoaceticus-baumannii complex.  Genomic species close to A. baumannii are 3 and 13TU, which are difficultly differentiated from A. baumannii .  In consideration of the difference on pathogenesis, easy differentiation method practicable in medical laboratories should be developed.

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