β-Lactam resistance in Haemophilus influenzae

• Main Author: Vali, Leila
• Published: University of Edinburgh 2005
• Subjects: 616.9
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.663170

<I>Haemophilus influenzae</I> is the most important pathogen of <I>Haemophilus</I> genus in humans. Resistance to β-lactams has been documented in this species, however, most β-lactam antibiotics are still widely used for treatment of <I>H.influenzae</I> infections. In order to minimise treatment failure, the anti-microbial efficiency of drugs should be monitored regularly. In this study the prevalence of β-lacam resistance in clinical strains of <I>H.influenzae</I> was determined in Scotland. Six hundred and sixteen isolates were collected from four hospitals during 1993-1995. 20.5% of the strains contained a β-lactamase enzyme. There are marked regional differences in the proportion of β-lactamase producing isolates which ranges from 9.6% in Glasgow Royal Infirmary to 33.3% in Edinburgh Royal Infirmary. The concentrations required for ampicillin, amoxycillin/clavulanic acid, cefuroximine, ceftazidime, cefotaxime, cefaclor and imipenem to inhibit 50% and 90% of the isolates were determined and compared to the surveys in other countries. <I>H.influenzae</I> biotypes I, II and III are the most prevalent biogroups in Scotland especially among the over 50 year old adults. β-lactam resistance was observed in all biogroups of <I>H.influenzae</I>. Among the clinical isolates, one strain from Glasgow Southern General Hospital, although remained sensitive to ampicillin, was found to be β-lactamase positive. A cell free extract of this strain was examined by isoelectric focusing and β-lactamase activity was visualised at a pI of 7.9. This novel enzyme, VAT-1, did not cofocus with any of the controls or any of their extended spectrum derivatives, nor was it indicative of plasmid encoded β-lactamases associated with other respiratory pathogens. Biochemical analysis indicated that VAT-1 had a substrate profile of a cephalosporinase that hydrolysed first generation cephalosporins. Inhibitor analysis demonstrated that VAT-1 was a class C β-lactamase and it is only the third β-lactamase that has been described in <I>H.influenzae</I>.