Pharmabiz
 

Tackling beta-lactamase bugs

Dr Mahender NayakThursday, December 1, 2005, 08:00 Hrs  [IST]

The emergence of ESBL producing organisms presents significant diagnostic and therapeutic challenges in the management of infections. Infection with ESBL producing bacteria results in prolonged hospital stay, increased costs and fatal consequences, with a reported mortality rate between 15-46%. Beginning with the introduction of penicillin half a century ago, the beta -lactams have remained the largest antibiotic class of clinical relevance, comprising four major families: the penicillins, cephalosporins, carbapenems and monobactams. In 1983 the plasmid-mediated ESBL enzymes were first observed in Germany. Since then, the number and variety have increased rapidly and their distribution is now worldwide. In India, ESBL producing gram-negative bacteria -commonly Klebsiella pneumoniae, Escherichia coli and other species of Enterobacteriaceae -are rapidly emerging therapeutic challenge, escalating in hospitals and emerging in the community with an incidence rate as high as 59 to 68% in hospital settings. Global incidence varies between 5% in the US to 11% in Europe. These gram-negative bacteria produce enzymes that break down beta-lactam antibiotics, that include all penicillins, cephalosporins and monobactams (aztreonam) and render them ineffective with the exception of the carbapenem group (Meropenem and Imipenem) that are considered as the drugs of choice From several documented accounts, a definite pattern is beginning to emerge; while there is evidence that these organisms can spread from hospital to hospital (making infection-control measures relevant to their containment), cases are now being seen in the community that is spilling over to the hospitals and vice versa. Common infections with ESBL-producing organisms include hospital-acquired infections, especially in the ICUs, hospital acquired pneumonia, septicaemia, peritonitis, intra-abdominal abscesses, UTI and bacterial meningitis. Due to the poor prognosis for patients and limited number of treatment options available, detection and prevention of ESBL infections remain of primary importance. Unfortunately, clinically relevant ESBL mediated resistance is not always detectable in routine susceptibility tests. Many clinical microbiology laboratories continue to mistakenly report these gram-negative bacillary isolates as susceptible to cephalosporins, penicillins and monobactams due to difficulties in clearly identifying isolates that possess these ESBLs. An essential component to the control of these outbreaks has included the judicious use of antibiotics, that would mean, a reduction and even elimination of use of cephalosporin and beta-lactamase inhibitor combinations and concomitant substitution with drugs such as carbapenems that are more stable against beta-lactamase patterns including ESBLs. According to the National Standard Methods guidelines 2005 developed by the Health protection agency - UK, two approaches have shown promise. The first strategy involves the use of carbapenems in serious infections due to ESBLs, while the second involves adherence to basic infection control guidelines together with local, relevant, timely, and robust surveillance involving clinicians. - (The author is Therapy Area Leader - Critical Care, AstraZeneca Pharma, India Ltd)

 
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