1942, Selman Maksman coined the word antibiotics. They are substances that are produced by microorganisms. They either slow down the growth of other bacteria or kill them right away. Examples include the beta-lactam antibiotics which consist of the penicilins. Others include the Carbapenems, the cephalosporins, the aminoglycosides, quinolones, sulfonamides and the oxazolidinones. Also, they could be classified as either bacteriostatic agents that slow down or inhibit the growth of bacteria or bactericidal agents which kill bacteria. Their discovery and use in medical science is of immense magnitude. They equally reduce the rate of mortality and morbidity of patients infected by bacteria. Their mode of administration could be oral, intravenous or even topical.
Timing of the dosing interval is dependent on; likelihood of toxicity to the patient, patients age and weight, cost of the drug, drug adherence, possibility of adverse drug interactions within the system, severity of the infection, site of the infection, route of drug administration, the most likely causative organism, the pharmacokinetics which includes the administration, distribution, metabolism and elimination of the antibiotics.
Patient’s age and weight are both important. For the paediatric age group, the age and weight are used in calculating the dosage of the antibiotics. The dosage in conjunction with the infecting organism(s) and the severity of the infection are used to calculate the dosing intervals. Those that are severely ill are often times infused with intravenous antibiotics so as to eliminate the slow absorption associated with oral administration of drugs. In such cases, the dosing interval could be altered from the conventional so that the therapeutic levels are achieved quickly.
Toxicity is very important in formulating dosing intervals. Especially when the patient is being given more than one antibiotic. Also, toxicity should be borne in mind in cases of severely ill and debilitated patients. They are likely to have weakened or already damaged organs. Hence, least toxic effects is a major factor in determining the dosing interval.
Cost of the antibiotics is another major factor in determining the dosing interval. If an antibiotic is a bit expensive, the likelihood that the patient stops taking the drugs when he or she is relieved is high. To prevent this, another antibiotic which is cheaper and is equally effective against the offending organism(s) is prescribed.
The moment an antibiotic is chosen based on suspicion or identification of the offending organisms through culture and sensitivity, the goal of therapy is the delivery of the antibiotic to the infection site. For antimicrobial therapy to be effective, the antibiotic must be greater than the MIC (Minimal Inhibitory Concentration) of the pathogens at the infection site. Hence, a factor in determining dosing intervals. Some antibiotics like the B- Lactams make no difference even with higher levels of MIC, but once the steady state is achieved and maintained higher than the MIC, efficacy is increased.
Drug administration either through the intravenous route, oral and intramuscular route determine the dosing interval. Antibiotic administration through the intravenous route goes directly into the bloodstream, has a faster onset of action, and therapeutic levels are achieved quicker than intramuscular and oral. The dosing interval is likely to be longer than intramuscular and oral. Antibiotics taken through the intramuscular route are likely to be twice daily compared to thrice or more of the oral route.
Drug delivery to the infection site is dependent on circulation. Once the antimicrobial agent gets to the blood stream, it gets to the infection site. In a situation where the infection site is poorly vascularised, drug delivery is compromised and the effective concentrations may not be achieved. To overcome this, the dosage and the number of times the drug is administered can be increased as long as the therapeutic index is safe.
In conclusion, the dosing interval is dependent on factors such as seriousness of the infection, offending pathogens and the pharmacokinetics of the drug. Effective dosing interval will in no small means cure the patient of the infection.
M Trexler Hessen and Kaye Principles of use of antibacterial agents Infectious Disease Clinics of North America Infect Dis Clin N Am 18 (2004) 435–450
T O'Callaghan (2012) Should weight factor into antibiotic dosage http://healthland.time.com/2010/01/14/should-weight-factor-into-antibiotic-dosage/
Richard Quintilani Pharmacodynamics of Antimicrobial Agents: Time-Dependent vs Concentration-Dependent http://www.antimicrobe.org/history/pk-pd%20quint.asp
C McKenzie (2012) Antibiotic dosing in critical illness http://jac.oxfordjournals.org/content/66/suppl_2/ii25.full