Download Printable Version

Write short notes on antimicrobial resistance with reference to:
(a)
(b)
(c)
Tuberculosis
Malaria
Staphylococcal infection
Outline:
 Mechanism of resistance
 Drugs in which resistance has developed
 Alternative drugs
Suggested Answer:
(a)
Multiple-drug resistance (MDR) explains the reason in the emergence of resistant strains of
mycobacteria in up to 70% of patients after 3 months of therapy. Multiple-drug resistance in
mycobacteria is apparently the result of the step-wise accumulation of resistance to individual drugs.
For example, mutations in the catG and inhA genes are associated with isoniazid resistance, while
the rpoB gene responsible for RNA polymerase is altered in many clinical isolates resistant to
rifampin. The threat of drug-resistant tuberculosis has made susceptibility testing mandatory for all
initial isolates. Antimicrobial resistance to tuberculosis is often the result of non-compliance of
patients which allow drug-resistant strains to survive and grow at a later date. Directly observed
therapy (DOT) has been instituted in high prevalence areas, especially among recalcitrant patients,
as the only reliable means of ensuring that patients complete their treatment successfully. Resistance
to the first-line drugs of isoniazid, ethambutol, rifampicin and pyrazinamide is common and secondline drugs such as ethionamide, amikacin, ofloxacin and cycloserine may have to be used.
(b)
Resistance of malaria parasites to antimalarials may be complete or relative; relative
resistance can be overcome by raising the dose of the antimalarial. The choice of blood
schizonticide depends upon the clinical condition of the patient, infecting species and possibility of
drug resistance. Parenteral therapy is reserved for patients unable to take medications by mouth and
for those with complicated malaria. Chloroquine-resistant P falciparum is widespread and currently
exists in all malarious areas of the world except Mexico, Central America, the Caribbean and parts
of the Middle East. P falciparum resistant to multiple drugs is most prevalent in S.E. Asia but is also
present in Africa and Brazil. Therapy of chloroquine-resistant P falciparum is complicated and
depends primarily on area of disease acquisition. Patients with uncomplicated disease acquired in
areas of chloroquine resistance can be treated with one of several regimens effective against
chloroquine-resistant parasites: mefloquine alone, or quinine, plus doxycycline or
pyrimethamine/sulfadoxine (FansidarR). Other effective drugs include halofantrine, artemisinin
(qinghaosu) derivatives, and clindamycin. Chloroquine-resistant P vivax is prevalent on the island of
New Guinea. Primaquine-resistant P vivax is most prevalent in S.E. Asia and Oceania and is
reported from other areas. Halofantrine, and chloroquine plus primaquine are highly effective
against these resistant strains. Drug resistance has not been reported for P ovale or P malariae. If
ever in doubt as to infecting species or presence of resistance, clinicians should assume the infection
to be chloroquine-resistant P falciparum. Such therapy will cover all malaria species, although side
effects may be more common.
(c)
Most staphylococci strains are now resistant to penicillin by producing a bete-lactamase
enzyme which destroys penicillin. Alternative antibiotics such as cloxacillin, nafcillin, erythromycin
and cephalosporins have been used to treat staphylococcal infection. However, hospital strains of S
aureus are often resistant to many different antibiotics. Indeed strains resistant to all clinically useful
drugs, apart from the glycopeptides vancomycin and teicoplanin, have been described. The term
MRSA refers to methicillin resistance and most methicillin-resistant strains are also multiply
resistant. Plasmid-associated vancomycin resistance has been detected in some enterococci and the
resistance determinant has been transferred from enterococci to S aureus in the laboratory and may
occur naturally. S epidermidis nosocomial isolates are also often resistant to several antibiotics
including methicillin. In addition, S aureus expresses resistance to antiseptics and disinfectants, such
as quaternary ammonium compounds, which may aid its survival in the hospital environment.
Since the beginning of the antibiotic era S aureus has responded to the introduction of new
drugs by rapidly acquiring resistance by a variety of genetic mechanisms including acquisition of
extrachromosomal plasmids or additional genetic information in the chromosome via transposons or
other types of DNA insertion and by mutations in chromosomal genes.
There are essentially four mechanisms of resistance to antibiotics in staphylococci:
enzymatic inactivation of the drug, alterations to the drug target to prevent binding, accelerated drug
efflux to prevent toxic concentrations accumulating in the cell, and a by-pass mechanism whereby
an alternative drug-resistant version of the target is expressed. Numerous approaches have been tried
to prevent the spread of antibiotic resistance such as isolation of patients with resistant organisms,
use of narrow-spectrum antimicrobial agents and rotating the range of agents available.