• In Vivo – three way struggle between the host, microbe and the drug; drug dosing must account for bacteria and antimicrobial agents in man, the metabolism of the drugs, and the organisms defenses against the hosts attack
• In Vitro – static lab test, artificial situation which does not represent the host environment
• Minimal inhibitory concentration (MBC) – the lowest concentration of antibiotic sufficient to inhibit bacterial growth
• Minimal bactericidal concentration (MBC) – the lowest concentration of antibiotic sufficient to kill bacteria plate and counting the number of colonies formed
• Killing curve – a known number of bacteria are inoculated into liquid media containing antibiotic(s) in varying concentrations and at frequent intervals, an aliquot of the mixture is removed and plated and a colony count is performed to reveal the exact number of viable organisms remaining (expressed as a % of the original inoculum)
• Bacteriostatic – agents that cause an organism to cease growth and multiplication, but do not kill it
• Bactericidal – agents that render organisms nonviable, even after the drug is taken away
• in vivo, the distinction between bacteriostatic and bactericidal is not straight forward, and an agent may be static is some situations and cidal in others depending on the drug concentration and host defenses

Chemoprophylaxis – administration in the absence of infection or contamination

• most successful when a single drug is given to prevent infection by a specific organism
• antimicrobial prophylaxis is not effective against viral disease; it is also not effective in clean abdominal surgery and CHF because infections may be caused by multiple agents and a specific bacteria can not be targeted
• with "blanket" coverage one agent is likely to fail causing an Ý infection rate; the organisms also become resistant
• Antimicrobial prophylaxis for surgical wounds – only necessary for a surprisingly short period of time
• helpful for hysterectomy, C-section, microneurosurgical craniotomy, biliary tract surgery and total joint replacements
• ß post-op wound infections, but must weigh against the risks of drug side effects
• clean wound operations do not benefic from systemic prophylactic antibiotics
• EXAMPLES OF MEDICAL ANTIMICROBIAL PROPHYLAXIS:

• Colonization versus Superinfection – antimicrobial agents later the normal resident flora and can encourage the overgrowth of resident bacteria such as staphylococci, gram (-) rods and yeasts
• if infection occurs then cultures are performed to determine if the organism is part of the normal flora Þ continued recovery of an organism, sensitive to the antimicrobial agent the patient is receiving, suggests the organism is a colonizer rather than a pathogen
• "Committed" inflammation – fever is a process of inflammation rather than a process of infection and treatment with an antibiotic may ß the infection, but many not ß the inflammatory process
• Antibiotic-resistant bacteria are usually less virulent
• slower growth rate, ß output of pathogenic enzymes, altered biochemical profile
• so why are they are problem? Þ they attack immunocompromised
• Subinhibitory Antibiotic Concentrations
• 1/2 MIC – concentrations do not inhibit bacterial growth but produce profound morphologic, biochemical alterations
• alter adherence to target cells and alter resistance to phagocytosis which may be enough to control the infection
• Clinical examples of synergy, antagonism
• used initially in seriously ill patients (before a diagnosis is established) to prevent superinfection, to delay the emergence of resistant bacteria (tuberculosis), in mixed infections (peritonitis) or to achieve synergy vs. resistant bacteria (enterococcal endocarditis)
• multiple bacteriostatic antibiotics may be worse in situations where the drugs poorly penetrate the area of infection (meningitis or endocarditis); chloramphenicol and ampicillin together have been show to produce worse results than ampicillin alone in the treatment of bacterial meningitis in children
• Dangers of Antibiotic Overuse – Ex of a Klebsiella aerogenes outbreak in Glasgow
• Prophylactic broad-spectrum antibiotics (ampicillin, cloxacillin) were routinely prescribed to patients considered at high risk of meningeal infection in the Glasgow Institute of Neurological Sciences. Due to this widespread use of antibiotics, from 1967-1969 there was a huge outbreak of Klebsiella aerogenes highly resistant to most antibiotics. After temporarily closing the wards and many attempts to eradicate the organism with Ý antibiotic usage, the institute realized that the organism was probably an opportunistic organism colonizing the respiratory tracts of patients whose normal bacterial flora had been suppressed by the broad-spectrum antibiotics. They decided to discontinue the use of both prophylactic and therapeutic antibiotics and there was an immediate ß in incidence of Klebsiella infections.