AMR: An Emerging Threat

Leprosy

Drug resistance has also come up in Leprosy. Earlier it occurred due to Dapsone monotherapy, but now is has been reported even after MDT [5]. Rifampicin (rpoB gene mutation) and Ofloxacin resistances are common (gyrA gene mutation).

Candida auris: Candida auris is a drug resistant and highly persistent yeast pathogen, discovered from the external ear of a person in 2009 in Japan [6]. Based on the CDC guidelines, about 90%, 30%, and 2% - 10% of  C.  auris  isolates are resistant to three major antifungal drug groups viz. fluconazole (FLU), amphotericin B (AMB), and echinocandins, respectively. Taken together, about 90% of C. auris strains are resistant to at least 1 drug, 30% - 41% to 2 drugs and about 4% to all 3 aforesaid antifungals [7]. It is highly prevalent in hospital settings like High Dependency Unit (HDU) and Intensive Care Unit (ICU). Patients may be colonized asymptomatically by C. auris on their skin, or in oropharynx, nostrils, rectum and other body sites. However, unlike most other  Candida  species, that colonize the gastrointestinal tract, C. auris predominately tends to colonize the skin [8]. C. auris grows appreciably at 40–42°C and is also able to survive in the environment and under alkaline conditions, although it does not tolerate anaerobiosis. The transformation of C. auris from an environmental fungus to a human pathogen is possibly due to the overuse of antifungals or due to the thermal adaptation owing to climate change.

Hence AMR is really a very serious public health problem now and hence it needs to be understood and mitigated. Also important is to know the mechanisms leading to AMR.

Mechanisms of AMR

• Mutations in drug target: This is commonly seen in cases of aminoglycoside and macrolide resistance in bacteria.
• Altered drug binding sites: MRSA is a good example of alteration of target site. Here the PBP or penicillin binding protein is altered to PBP-2a which does not effectively bind beta-lactam antibiotics.
• Drug modifying enzymes: Aminoglycoside modifying enzymes confer resistance to these antibiotics in Enterococci and other bacteria. In fact, aminoglycoside modifying enzymes are responsible high level aminoglycoside resistance (HLAR) in Enterococcus spp. This phenomenon renders the synergistic activity of bet- lactams and aminoglycosides on Enterococci ineffective [9]. Such modifying enzymes include acetyltransferases, phosphotransferases, and nucleotidyltransferases which can alter the effects of other aminoglycosides. Recently, a new antibiotic has been discovered, namely Plazomicin, which is not affected by aminoglycoside-modifying enzymes [10].
• Efflux pumps:- Tet efflux pumps mediate Tetracycline resistance in Staphylococcus aureus. Efflux pumps may also be important for Plazomicin resistance in Enterococci. These efflux pumps belong to the major facilitator superfamily of transporters, and are able to effectively decrease intracellular tetracycline concentration via exchange of a tetracycline molecule against a proton [11]. Also, tetracycline efflux genes are associated with mobile genetic elements, like plasmids or transposons, which helps in their wide dissemination across species or genus boundaries.
• Thickened cell wall impeding penetration of drug into target site:- This is seen in VISA or Vancomycin indeterminate Staphylococcus aureus. A thick cell wall impairs the entry f Vancomycin into target site. Also, increased cell wall turnover can be responsible.
• Intrinsic drug resistance:- Gram negative bacteria are always resistant to Vancomycin. Enterococus casseliflavus is always inherently resistant to Vancomycin. This resistance can be mediated by the vanC gene. The vanC resistance determinants are found on the chromosome in Enterococcus casseliflavus and Enterococcus gallinarum and are intrinsic characteristics of these species. VanC- harboring enterococci exhibit low-level resistance to vancomycin and are generally susceptible to teicoplanin [12]. Among yeasts, Candida krusei in intrinsically resistant to Fluconazole. The Table 1 below shows illustrative tabulation of infection, resistance to drugs and the mechanisms.

How to Reduce the Burden of AMR in the Community

Some steps can be taken to recue AMR burden in community, like:- I. Proper awareness needs to be generated about AMR in the community. Even today, many common people think that Paracetamol and Cetirizine are antibiotics. II. Resistance to antibiotics is very common in the community. In our experience, Nitrofurantoin resistance in uropathogenic Escherichia coli is not low (27.27%). This means that commonly used empiric drugs can no longer be safely used for treating common ailments like urinary tract infections. III. Data on antibiotic susceptibility patterns over time should be sought and antibiotics changed accordingly. Genetic methods should be used for surveillance of drug resistance, more commonly in Mycobacterium tuberculosis and M. leprae. Such methods include NAAT (Nucleic acid amplification tests)/PCR and Whole genome sequencing.

How to Reduce Burden of AMR in the Hospital

Some things have to be remembered and implemented for infection control in the hospital settings, like:- A. Proper antibiotic stewardship has to be there, along with other things that should be emphasized, like proper biomedical waste disposal and vaccination to prevent infections. B. Hand hygiene is also very important to prevent cross- transmission of resistant bugs(6 steps and 5 points of hand hygiene have to be kept in mind). C. Operation theatres should be kept free of trespassers as far as possible to prevent nosocomial infections by multidrug-resistant bugs. Air and surface microbial flora of operation theatres should, hence always be assessed before commencement of any operational procedure. D. Each hospital should have its own antibiotic registry and also do regular antibiotic audit. Also, periodical antibiotic ward rounds should be carried out to assess and ensure proper usage of antibiotics in the wards. E. Cleaning and disinfection should be stressed upon. Hydrogen peroxide and Povidone Iodine are good at reducing the burden of C. auris in hospitals by killing planktonic and biofilm cells of C. auris [13]. F. No cobweb should be allowed in hospitals to prevent accumulation of dirt and along with that, multidrug resistant microbes. For this reason only, hospital flooring should also be seamless wherever possible. G. Each hospital/healthcare facility should have its own antibiotic policy which should be periodically revised. This policy should be created and maintained by ICC (Infection control committee) of the healthcare facility, comprising one clinician, one Microbiologist and one nursing staff, along with others. It is to be headed by the Medical Superintendent of the hospital or equivalent person.