The right drug for the right bug
Infection is a leading cause of morbidity and mortality in hospitals and empiric use of antibacterials is common. However, prescribers face a dilemma: initial antibacterial therapy must cover all the likely infective organisms for the presentation (inadequate initial therapy is associated with a poor outcome) but excessive use of broad-spectrum agents contributes to the selection of antibacterial-resistant organisms that are associated with increased morbidity, mortality and length of hospital stay. The 1998 House of Lords Select Committee on Science and Technology report into antimicrobial resistance estimated that up to 50 per cent of antimicrobials prescribed in hospitals may be inappropriate. This article aims to assist pharmacists in advising clinicians on choosing appropriate antibacterials.
Commensal or pathogen?
The human body carries a wide range of bacteria but few of these are able to cause infection in an immunocompetent host. Indeed, the majority are considered commensal or normal flora and can play an important role in host defence. For instance, eradication of the normal intestinal flora can permit overgrowth of pathogens such as Clostridium difficile, causing antibiotic-associated colitis. On the other hand, a commensal in the wrong place can be just as harmful as a true pathogen. For example, if Escherichia coli, an essential component of the intestinal flora, enters the bladder, a urinary tract infection can ensue.
Pathogens can produce a wide range of virulance factors, distinguishing them from commensals. Examples include the ability to interact with cell proteins, to adhere to host cells, to invade host cells to avoid phagocytosis or produce a polysaccharide capsule that gives protection from phagocytes. Examples of such encapsulated organisms include Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae.
Finally, some pathogens have the ability to produce either exotoxins (secreted during growth) or endotoxins (components of the Gram negative cell wall), which may be responsible for some, or all, of the clinical effects seen during infection.
Colonisation or infection?
The diagnosis of infection is often based on systemic signs, such as fever and tachycardia, and local symptoms, including production of coloured sputum, pain on urinating and white blood cells in the urine, and local erythema or presence of pus. Other investigations (eg, imaging and biopsies) can aid diagnosis. If a patient is colonised, as opposed to infected, such symptoms and signs are likely to be absent. Therefore, a nasal swab growing methicillin resistant Staphylococcus aureus (MRSA) is not grounds for treatment with intravenous vancomycin if the patient is otherwise well.
Raised white blood cell and platelet counts and elevations in inflammatory markers, such as C-reactive protein and erythrocyte sedimentation rate, can also suggest infection in an acutely ill patient, but the ability of an infection to mimic other conditions, such as connective tissue disorders (eg, systemic lupus erythematosus) or malignancy, introduces diagnostic uncertainty. In addition, some infective organisms can present in many ways. For example, S aureus can cause infections ranging from simple skin infections to septicaemia and toxic shock syndrome. It is also important to recognise that immunocompromised or severely ill patients may not be able to mount the immune response that causes such symptoms and signs.
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Citation: The Pharmaceutical Journal URI: 10997308
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