Bacterial challenges and evolving antibacterial drug strategy.

In this paper, we attempt to summarize developments ofimportance for practising hospital clinicians and for primary care doctors who must be aware of the ever-widening spectrum of recognized pathogens. This article is restricted to considerations of pathogenic bacteria and antibacterial drugs that have obliged us to change our strategies or policies in the last decade or so. There have been many confusing developments. Whilst basically new antibacterial drugs are rare, variations on previously successful models have been very numerous and some significant progress has been made. Over the decade, several new infective challenges have posed problems for clinicians and microbiologists. It is recognized that communityacquired infections differ from hospital-acquired infections in the range and nature and antibiotic resistance profiles of the causative organisms. The inexorable progress of bacterial drug resistance has obliged us to reconsider first-choice therapy for some infections. Beta-lactamase production by various bacteria has restricted our therapeutic options or has obliged us to use new preparations. For example, our recognition of the pathogenic potential of Moraxella (Branhamella) catarrhalis has required modification of previous approaches to the antibiotic therapy of respiratory tract infections, and beta-lactamase-producing strains of Haemophilus influenzae have created further problems. Worrying outbreaks of a range of infections from legionellosis to salmonellosis have extended us to determine or define appropriate therapy. Our evolving awareness of human immunodeficiency virus (HIV) disease and associated opportunistic bacterial infections obliges us to consider a variety of new challenges, especially mycobacterial infections. Our relative lack of success in dealing with some aggressive infections, such as those caused by the meningococcus or Haemophilus influenzae, has called for a review of our prophylactic strategies, and this has been highlighted in the case of pneumococcal challenges in compromised (asplenic) patients. The common occurrence of polymicrobial or mixed bacterial infections has been acknowledged, and the neglected concept of pathogenic synergy has been revived. The problems of antibiotic-associated diarrhoea have necessitated scrutiny of precipitating antibiotics and studies of the most effective therapy. Meanwhile, the general acceptance of the principle of peroperative antimicrobial prophylaxis and its application to specific areas of operative surgery has had a major impact.