___________________________________________________________________________ Antibiotics Review
Various strategies have been employed to circumvent these microbial adaptations. Altering the structure of the penicil- lin molecule to produce agents that are more resistant to the hydrolysis from the beta-lactamases has resulted in the develop- ment of the extended-spectrum penicillins. Another strategy has been to combine penicillins with other agents that block bacterial beta-lactamases [6]. Examples include amoxicillin plus clavulanic acid, ampicillin plus sulbactam, piperacillin plus tazobactam, and ticarcillin plus clavulanic acid. Clavulanic acid is produced by Streptomyces cla- vuligerus . Sulbactam and tazobactam are derived from the basic penicillin ring. These agents have little intrinsic antimicrobial activity, but they bind irreversibly to many beta-lactamases, preventing hydrolytic activity against the beta-lactam ring. PHARMACOKINETICS Penicillins can be separated into groups based on their phar- macokinetics and spectrum of antibacterial activity. These groups are the natural penicillins, the aminopenicillins, the penicillinase-resistant penicillins, and the antipseudomonal penicillins [15]. The Natural Penicillins The natural penicillins include various penicillin G prepara- tions and penicillin V potassium. Penicillin G is very unstable in stomach acid and must be given parenterally. Penicillin V potassium is more acid-stable and is the appropriate form for oral administration. The natural penicillins are active against gram-positive organ- isms such as streptococci, Enterococcus faecalis , and Listeria monocytogenes . However, most S. aureus isolates are now resis- tant. The natural penicillins are also active against anaerobic species, such as Bacteroides species and Fusobacterium species. At serum levels achieved by parenteral administration, the natural penicillins are effective against some gram-negative bacteria, such as Escherichia coli , H. influenzae , Neisseria gonorrhoeae , and Treponema pallidum . For the treatment of moderate-to-severe infections in which resistant organisms are considered a pos- sibility, reliance upon penicillin alone should be avoided unless the identity and sensitivity of the infecting organism have been confirmed. Labeled uses include treatments for infections of the upper and lower respiratory tract, throat, skin, and geni- tourinary tract and prophylaxis of recurrent rheumatic fever and pneumococcal infections [6].
CONSIDERATIONS FOR NON-ENGLISH- PROFICIENT PATIENTS Obtaining a detailed patient history is a vital aspect of the appropriate prescription of antibiotics, particularly in empiri- cal treatment. Furthermore, communication with patients regarding treatment regimens and compliance depends on clear communication between the patient and clinician. When there is an obvious disconnect in the communication process between the practitioner and patient due to the patient’s lack of proficiency in the English language, an interpreter is required. The interpreter should be considered an active agent in the diagnosis and/or treatment processes, negotiating between two cultures and assisting in promoting culturally competent communication and practice [10]. PENICILLINS Alexander Fleming discovered penicillin in 1928. After observing that Penicillium colonies inhibited the growth of staphylococci on agar plates, Fleming made an extract from the mold and proved that it inhibited bacterial growth. Penicillin became available for general use in the 1940s [11]. MECHANISM OF ACTION Penicillin is bactericidal, killing susceptible bacteria by inter- rupting cell wall synthesis. The drug exerts its effect by prevent- ing cross-binding of the peptidoglycan polymers necessary for cell wall formation and by binding with carboxypeptidases, endopeptidases, and transpeptidase (“penicillin-binding proteins” [PBPs]) that participate in cell wall synthesis [12]. Although the exact mechanisms involved are not known, the result is that the cell wall is structurally weakened and lyses, leading to cell death. The basic form of penicillin is structured around the beta- lactam ring (a thiazolidine ring) and can be altered by substi- tuting side chains. By doing so, the antimicrobial spectrum, absorption characteristics, and resistance to beta-lactamase deactivation can be favorably modified. Bacterial resistance to penicillins may take different forms. The most significant is the bacterial production of beta-lactamases, which can destroy the beta-lactam ring by means of hydrolysis, effectively preventing antimicrobial activity by the agent [13]. In addition, some bacteria are able to prevent binding to the PBPs by various means, including altered binding sites for the penicillins [14].
91
EliteLearning.com/Dental
Powered by FlippingBook