Part I: Antibiotic resistance - Local scenario
1.6 Carbapenem-resistant Acinetobacter baumannii (CRAB)
Multidrug-resistant Acinetobacter baumannii (MRAB) is a widely used, and yet ill-defined and non-specific term (Figure 1.4). There is no internationally agreed definition for MRAB. Carbapenem is a critically important class of antimicrobial in the treatment of infection caused by Acinetobacter baumannii (86–87). Therefore, resistance to the carbapenems have been defined as a sentinel event (88–90). Using the term CRAB allows better communication and surveillance data could be comparable between different centres (Figure 1.4). Moreover, the recent rise in resistant strains of A. baumannii seen worldwide is mainly due to the dissemination of strains possessing the Class D OXA type ß-lactamase (91–94). Therefore, for surveillance purpose, the term CRAB reflects the current situation more accurately than MRAB. In February 2017, the World Health Organization published a list of antibiotic-resistant priority pathogen for which new antibiotics are urgently needed; the term CRAB is used.
- Resistance to carbapenem can be due to enzymatic degradation and efflux pump. However the recent spread in resistant strains of A. baumannii is mainly due to strains producing the class D OXA type ß-lactamase (95–96). OXA-23, OXA-24 and OXA-58 are the most common type of carbapenemase produced by A. baumannii. They contribute to carbapenem resistance in A. baumannii globally (96).
- The metallo-ß-lactamases are class B ß-lactamases which contain at least one zinc ion at their active sites (Table 1.8). They are more potent carbapenemases and can hydrolyse all ß-lactamase except the monobactam, aztreonam (96). However, metallo-ß-lactams is less commonly seen in A. baumannii. Due to the simultaneous presence of resistance determinants often carried on integrons, CRAB has concomitant resistance to other classes of antibiotics (19).
- In a local survey of CRAB in 2010, majority of the strains belonged to HKU1 and HKU2 clones (89). OXA-23 was found in all HKU1 isolates and correlated with high level of resistance to carbapenems. OXA-51 was found in both HKU1 and HKU2 clones. Chronic wounds were found to be associated with MRAB colonisation or infection, which acts as a potential reservoir for MRAB. This study demonstrated the spread of CRAB is due to the dissemination of two novel clones (91).
- Imipenem resistance was found to have a significant impact on the mortality of Acinetobacter bacteraemia (97), which is mainly accounted by the higher rate of discordant antimicrobial therapy. Acinetobacter resistant to imipenem was also found to have a higher rate of resistance to other classes of antimicrobial agents.
- There is an increasing endemicity of CRAB ST457 in HK, the incidence of CRAB bacteraemia was 0.27/100,000 patient-days in 2009. A rapid increase of incidence to 1.86/100,000 patient-days occurred in 2013. The increase in the absolute number of CRAB bacteraemia better reflects the true burden to the healthcare system caused by CRAB. Risk factors include resident of elderly home, use of carbapenem and ß-lactam/ß-lactamase inhibitor combinations 90 days before admission (98).
- A recent local study screened 17,760 faecal specimens for CRAB and MRAB from 9,469 patients over a 7-month study period in a 3,200-bed healthcare network. Screening result showed that 2.6% (244/9,469) patients were CRAB carriers, where 0.57% (54/9,469) were MRAB carriers. Quantitative bacterial counts in various body sites were performed in 33 of the 54 MRAB carriers. Use of fluoroquinolones 6 months before admission was the only significant factor associated with high bacterial load in nasal and rectal swabs (99).