CHAPTER 1: INTRODUCTION, LITERATURE REVIEW AND
1.2 Literature review
1.2.12 Problem statement
MDR, XDR and PDR Acinetobacter spp. isolates are on the rise worldwide (Begum et al., 2013;
Ogutlu et al., 2014) and pose a great challenge for physicians and clinical microbiologists regarding Antibiotic Stewardship Programs (ASWPs), both globally and locally. Successful ASWPs are crucial in making sure that available treatment options are preserved (Manchanda et al., 2010; Barlam et al., 2016). The emergence and spread of drug-resistant (MDR, XDR, PDR) Acinetobacter spp. are alarming, since the organism is responsible for many healthcare-associated infections (Manchanda et al., 2010; Gonzalez-Villoria and Valverde-Garduno, 2016; Samawi et al., 2016). Moreover, the resistance patterns of Acinetobacter spp. present a high-risk global infection control challenge (Coelho et al., 2006; Cheon et al., 2016). Despite the prevalence of infection, there is limited scientific data and a lack of a standardised management guideline to assist ASWPs and help the clinician select optimal therapy in local hospital settings.
32
ASWPs in hospitals aim to optimise antimicrobial prescribing so that individual patient care is improved, antimicrobial resistance is decreased and hospital costs are reduced (MacDougall and Polk, 2005). Guidelines from the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA) (2016) recommends preauthorisation and prospective review of antibiotics as a measure to improve the efficacy of ASWP (Barlam et al., 2016).
Preauthorisation means that providers need approval before prescribing antibiotics, while prospective audit allows antibiotic stewards to communicate with clinicians after the antibiotic has been used in order to optimise treatment. These strategies may be used alone or in combination to prevent antibiotic misuse and resistance. Hospitals should use one or both of these methods based on their local resources and expertise (Barlam et al., 2016). However, it is difficult to differentiate between isolates that cause sepsis versus colonisation when establishing the decision to treat, which is a major part of ASWPs (Swe Swe-Han and Pillay, 2015).
Although Acinetobacter was previously, and even now in some units, ignored when isolated from clinical samples, there are now over 1000 references to ‘infections and resistant Acinetobacter’
in the international literature. In addition, the type of infections caused by Acinetobacter has changed over the past 30 years (Joly-Guillou, 2005; Mathai et al., 2012; Begum et al., 2013;
Ogutlu et al., 2014). The literature has explored Acinetobacter spp. as a successful pathogen; its biological aspects; epidemiology and pathogenicity factors; global spread and surveillance and multilateral system and related outbreak investigation (Naas et al., 2005; Higgins et al., 2010;
Antunes et al., 2014; Kim et al., 2015). The literature shows that standard treatment and clinical decisions are difficult in Acinetobacter spp. infection due to its ability to develop resistance with unusual resistance patterns, and lack of standard guidelines to determine significant infection (Ogutlu et al., 2014; Cheon et al., 2016). In order to plan health care policies, a standardised management approach and intervention measures need to be implemented to reduce Acinetobacter spp. sepsis in resource-poor settings. It is necessary to have evidence of the prevalence, proportion of sepsis and colonisation groups; drug resistance patterns; effectiveness of synergy of colistin with other drug combinations; and characterisation of Acinetobacter spp.
isolates in local hospitals to initiate the health care policies (Ntusi et al., 2012).
In the KZN province of South Africa, there is a paucity of such data and no guidelines to differentiate the Acinetobacter spp. isolates that cause infection versus colonisation. Data on the prevalence of resistance patterns of Acinetobacter spp. and their significance with regards to sepsis and colonisation is limited in South Africa.
33
The increasing prevalence of carbapenem-resistant Acinetobacter spp. isolates that are also resistant to all commonly available antibiotics is of particular concern. Colistin is the only drug of choice for the treatment of MDR Acinetobacter spp. (Moffatt et al., 2010). However, its resultant renal toxicity and neurotoxicity makes it an unattractive alternative (Arıdoğan, 2012).
In addition, Acinetobacter isolates that are resistant to colistin have also been observed (Moffatt et al., 2010). Therefore, therapy using combinations of antimicrobials (including carbapenems, colistin, rifampicin, and ampicillin-sulbactam) has been suggested as the best approach. The clinical utility of these combinations against PDR Acinetobacter spp. remains to be determined (Doughari et al., 2011). The limited available options are major concern and further work on the use and efficacy of combination therapies, as well as on clinical outcomes, is warranted (Doughari et al., 2011). The synergistic effects of colistin in combination with various other agents has been reported, but there is a lack of a standard approach in the treatment and management of infection (Almasaudi, 2016; Gonzalez-Villoria and Valverde-Garduno, 2016).
Drug-resistant Acinetobacter spp. presents a serious global infection control challenge (Fishbain and Peleg, 2010; Ghafur et al., 2014; Phee et al., 2015; Almasaudi, 2016). Previous studies have examined its spread and identified genes encoding drug resistance. However, characterisation of Acinetobacter spp. clinical isolates in the local academic hospital in Durban (South Africa) has not been previously reported.
With an exponential rise in infections over the past decade, clinicians and microbiologists face the task of choosing optimal antimicrobial agents for treatment regarding ASWPs. Antibiotic resistance is a major challenge to the healthcare system and it is difficult to provide optimal treatment options due to changes in resistance patterns, increased costs and the availability of new agents (Diekema et al., 2004; Fishbain and Peleg, 2010; Ghafur et al., 2014; Phee et al., 2015).
Historically, it has been shown that if an optimal antibiotics usage guideline is not developed, this can lead to overuse of antimicrobial agents and the loss of their efficacy (Ventola, 2015).
In order to address the above, this study investigated the clinical significance of Acinetobacter spp. infections; criteria for colonisation versus significant sepsis based on clinical and microbiological data, determined the most effective combinations of drugs and characterised Acinetobacter spp. isolates phenotypically and genotypically. A standard approach for the treatment and management of Acinetobacter spp. infections for community-centred academic complex hospitals was developed for implementation in the local setting. This was an analytical, observational, experimental study performed at the Microbiology laboratory, NHLS academic complex hospital IALCH, in Durban (South Africa). This research provides a valuable
34
standardised approach to assist the clinician to select optimal therapy in the form of a standardised algorithm for the management of patients with significant Acinetobacter spp. infections, including a synergy test protocol at this unit.