Table 3: The Bactericidal and Bacteriostatic Nature of Antibiotics Most Commonly Prescribed for the Treatment of Orofacial Infections Bactericidal Bacteriostatic • β -Lactam Antibiotics
• Clindamycin • Macrolides (erythromycin, clarithromycin, azithromycin) • Sulfonamides and Trimethoprim (Bactrim, Septra, Co-Trimoxazole) • Tetracyclines (tetracycline, doxycycline)
(amoxicillin, ampicillin, cloxacillin, cephradrine, cephalexin, cefadroxil, cefaclor, cefuroxime, dicloxacillin, penicillin G, penicillin VK) • Augmentin (amoxicillin plus clavulanate) • Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin) • Metronidazole
CONCENTRATION-DEPENDENT KILLING VERSUS TIME-DEPENDENT KILLING
Often, antibiotic failures are the result of inappropriately prescribing bacteriostatic antibiotics for the wrong indication or at the wrong (too low) dose. In the case of bactericidal agents, antibiotic failures are due primarily to inappropriate prescribing (typically a mismatch between an antibiotics’ spectrum of activity and the pathogens intended to be eradicated – in other words, “the wrong drug for the right bug”). Bactericidal antibiotics exert either concentration-dependent killing (e.g., the fluoroquinolones and metronidazole) or time-dependent killing (e.g., all β -lactam antibiotics: penicillins, cephalosporins, and amoxicillin/clavulanic acid). Concentration-dependent killing occurs with antibiotics that can achieve high concentrations The drugs While there are many antibiotics available, in the case of orofacial infections, the prudent prescriber need focus on only a handful of pertinent drug classes based on their spectrum of activity and the anticipated pathogens: penicillins, cephalosporins, tetracyclines, macrolides, fluoroquinolones, and nitroimidazoles. Interestingly, a recent systematic review published by Martins et al. (2017), which included over 1100 articles, found that in the case of dental infections, once drainage has been performed and/or the cause of infection has been removed, all antibiotics tested are equally effective with respect to clinical cure and that the choice of antibiotics is not as successful as the local intervention treatment procedure. Once the need for antibiotic therapy is detected, antibiotics should be used for the shortest time possible until the patient’s clinical cure is achieved (Martins et al., 2017). Table 2 describes the spectrum of activity for these most commonly used antibiotics in treating orofacial infections and the most common individually prescribed drugs within each drug class. Table 3 further categorizes these drug classes and the individual specific drugs in each category as either bactericidal or bacteriostatic in their action. Penicillins Penicillin is a narrow-spectrum antibiotic because it mainly targets gram-positive aerobic and facultative bacteria ( Staphylococcus spp., Streptococcus spp., Listeria ), most anaerobes (with certain exceptions, such as Bacteroides ), and spirochetes (B rachyspiraceae, Leptospiraceae, and Spirochaetaceae ). It is still considered the drug of choice for streptococcal infections and causes bacterial lysis by interfering with the synthesis of peptidoglycan, which is necessary for the formation of the bacterial cell wall. Penicillin G is the progenitor and is considered the “gold standard,” hence the inclusion of the initial “G” for “gold.” It is typically given parenterally, bypassing the alimentary tract, because it is unstable in the highly acidic environment of the stomach. Penicillin VK (penicillin V potassium) is the orally-stable formulation of penicillin G. The “V” comes from the Latin verb vesco/vescar , meaning, “eat.” Penicillins are sometimes referred to as β -lactam antibiotics because their chemical structure contains a β -lactam ring. β -lactam antibiotics inhibit the formation of peptidoglycan
at the infection site (i.e., greater than 10 times the minimum inhibitory concentration [MIC] of the infecting organism). Their rate and extent of microbial killing increases with increasing drug concentration, and these antibiotics can typically be administered just once or twice a day. Antibiotics that exert time-dependent killing must be given more frequently since their bactericidal activity does not rely so much on the size of the dose administered, but on how long the drug concentration is maintained above the minimum bactericidal concentration (MBC). This explains why, even today, penicillin G and penicillin VK cannot be given as one single large dose, but require re- dosing every 6 to 8 hours to be effective. cross-links in the bacterial cell wall, causing bacterial death via inhibition of cell wall synthesis. Cephalosporins Cephalosporins such as cephalexin are also called β -lactam antibiotics , based on their similar chemical structure, which causes them to have an analogous mechanism of action to penicillins. While all β -lactam antibiotics kill bacteria by the same mechanism of action, it is their individual chemical structures that determine their spectrum of activity. Ampicillin and amoxicillin are extended-spectrum penicillins, while the combination of antibiotics such as amoxicillin with the β -lactamase inhibitor clavulanate (Augmentin ® ) helps create a broad-spectrum antibiotic ( β -lactamase is an enzyme that some bacteria have developed to help resist the effects of β -lactam antibiotics). Nitroimidazoles, clindamycin, and the macrolides Other narrow-spectrum antibiotics include metronidazole (a nitroimidazole antibiotic); clindamycin (a lincosamide antibiotic); and the macrolides antibiotics erythromycin, clarithromycin, and azithromycin. Metronidazole is active only against obligate anaerobic bacteria such as such as Bacteroides, Campylobacter, Clostridium, Fusobacterium, Peptostreptococcus, Prevotella , and Veillonella , in which it interferes with nucleic acid synthesis, causing microbial death. Clindamycin and the macrolide antibiotics inhibit bacterial protein synthesis by affecting the function of 30S or 50S ribosomal subunits, leading to bacterial cell death. However, clindamycin has better activity against most strains of Staphylococcus aureus and is more active against gram-positive and gram-negative anaerobes. The macrolides are more effective against Streptococcus pneumoniae , as well as other typical ( Haemophilus influenzae and Moraxella catarrhalis ) and atypical ( Legionella pneumophila, Mycoplasma pneumoniae, Chlamydophila pneumoniae ) upper respiratory tract pathogens. Fluoroquinolones and tetracyclines The fluoroquinolones (e.g., ciprofloxacin, levofloxacin, moxifloxacin) are extended-spectrum antibiotics that act by interfering with bacterial nucleic acid synthesis. These agents are not typically used as first-line agents for orofacial infections, although ciprofloxacin may have a role in treating susceptible species of Pseudomonas . The fluoroquinolones and broad-
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