2. transfer of resistance between organisms can occur by transfer of naked DNA (transformation), by conjugation with direct cell-to-cell transfer of extrachromosomal DNA (plasmids), or by passage of the information by bacteriophage (transduction). In this way, transfer of genetic information concerning drug resistance (frequently to a group of several antibiotics simultaneously) may occur between species. Mechanisms of drug resistance can be broadly divided into three groups: 1. inactivation of the antimicrobial agent either by disruption of its chemical structure (e.g. penicillinase) or by addition of a modifying group that inactivates the drug (e.g. chloramphenicol, inactivated by acetylation); 2. restriction of entry of the drug into the bacterium by altered permeability or efflux pump (e.g. sulphonamides, tetracycline); 3. modification of the bacterial target – this may take the form of an enzyme with reduced affinity for an inhibitor, or an altered organelle with reduced drug-binding properties (e.g. erythromycin and bacterial ribosomes). DRUG COMBINATIONS Most infections can be treated with a single agent. However, there are situations in which more than one antibacterial drug is prescribed concurrently: • to achieve broad antimicrobial activity in critically ill patients with an undefined infection (e.g. aminoglycoside plus a penicillin to treat septicaemia); • to treat mixed bacterial infections (e.g. following perforation of the bowel) in cases where no single agent would affect all of the bacteria present; • to prevent the emergence of resistance (e.g. in treating tuberculosis; see Chapter 44); • to achieve an additive or synergistic effect (e.g. use of co-trimoxazole in the treatment of Pneumocystis carinii pneumonia). PROPHYLACTIC USE OF ANTIBACTERIAL DRUGS On a few occasions it is appropriate to use antibacterial drugs prophylactically. Wherever possible a suitably specific narrowspectrum drug should be used. ANTIBIOTIC PROPHYLAXIS OF INFECTIVE ENDOCARDITIS An important recent change is that fewer patients are deemed to require antibiotic prophylaxis against infective endocarditis; it should be restricted to patients who have previously had COMMONLY PRESCRIBED ANTIBACTERIAL DRUGS 325 endocarditis, cardiac valve replacement surgery (mechanical or biological prosthetic valves), or surgically constructed systemic or pulmonary shunts or conduits. In such patients, all dental procedures involving dento-gingival manipulation will require antibiotic prophylaxis, as will certain genito-urinary, gastrointestinal, respiratory or obstetric/gynaecological procedures. Intravenous antibiotics are no longer recommended unless the patient cannot take oral antibiotics. The latest guidelines (2006) by the Working Party of the British Society for Antimicrobial Chemotherapy can be found at http://jac.oxfordjournals.org/ cgi/reprint/dkl121v1. These are updated periodically. For dental procedures, in addition to prophylactic antibiotics, the use of chlorhexidine 0.2% mouthwash five minutes before the procedure may be a useful supplementary measure. PROPHYLACTIC PREOPERATIVE ANTIBIOTICS GENERAL PRINCIPLES 1. Prophylaxis should be restricted to cases where the procedure commonly leads to infection, or where infection, although rare, would have devastating results. 2. The antimicrobial agent should preferably be bactericidal and directed against the likely pathogen. 3. The aim is to provide high plasma and tissue concentrations of an appropriate drug at the time of bacterial contamination. Intramuscular injections can usually be given with the premedication or intravenous injections at the time of induction. Drug administration should seldom exceed 48 hours. Many problems in this area arise because of failure to discontinue ‘prophylactic’ antibiotics, a mistake that is easily made by a busy junior house-surgeon who does not want to take responsibility for changing a prescription for a patient who is apparently doing well post-operatively. Local hospital drug and therapeutics committees can help considerably by instituting sensible guidelines on the duration of prophylactic antibiotics. 4. If continued administration is necessary, change to oral therapy post-operatively wherever possible. The British National Formulary provides a good summary of the use of antibacterial drugs preoperatively, which may be varied according to local guidelines based on regional patterns of bacterial susceptibility/resistance. COMMONLY PRESCRIBED ANTIBACTERIAL DRUGS β-LACTAM ANTIBIOTICS These drugs each contain a β-lactam ring. This can be broken down by β-lactamase enzymes produced by bacteria, notably by many strains of Staphylococcus and Haemophilus influenzae, which are thereby resistant. β-Lactam antibiotics kill bacteria by inhibiting bacterial cell wall synthesis. Penicillins are excreted in the urine. Probenecid blocks the renal tubular secretion
326 ANTIBACTERIAL DRUGS of penicillin. This interaction may be used therapeutically to produce higher and more prolonged blood concentrations of penicillin. Antibiotics in this group include the penicillins, monobactams, carbapenems and cephalosporins. PENICILLINS Use Benzylpenicillin (penicillin G) is the drug of choice for streptococcal, pneumococcal, gonococcal and meningococcal infections, and is also useful for treatment of anthrax, diphtheria, gas gangrene, leptospirosis, syphilis, tetanus, yaws and Lyme disease in children. Adverse effects The adverse effects include: 1. anaphylaxis (in approximately 1 in 100 000 injections); 2. rashes (3–5% of patients) can, rarely, be severe (e.g. Stevens–Johnson syndrome – see Chapter 12); 3. serum sickness – type III hypersensitivity; 4. other idiosyncratic reactions including haemolytic anaemia and thrombocytopenia; 5. in renal failure, high-dose penicillin causes encephalopathy and seizures. Limitations of benzylpenicillin include: 1. It is acid labile and so must be given parenterally (inactivated in gastric acid). 2. It has a short half-life, so frequent injections are required. 3. Development of resistant β-lactamase-producing strains can occur. 4. It has a narrow antibacterial spectrum. Two preparations with similar antibacterial spectra are used to overcome the problems of acid lability/frequent injection: 1. Procaine benzylpenicillin – this complex releases penicillin slowly from an intramuscular site, so a twice daily dosage only is required. 2. Phenoxymethylpenicillin (‘penicillin V’) – this is acid stable and so is effective when given orally (40–60% absorption). Although it is useful for mild infections, blood concentrations are variable, so it is not used in serious infections or with poorly sensitive bacteria. Tablets are given on an empty stomach to improve absorption. β-LACTAMASE-RESISTANT PENICILLIN Flucloxacillin was developed to overcome β-lactamase-producing strains. Otherwise, it has a similar antibacterial spectrum to benzylpenicillin. It is effective against β-lactamase-producing organisms. It is used for the treatment of staphylococcal infections (90% of hospital staphylococci are resistant to benzylpenicillin and 5–10% are resistant to flucloxacillin). EXTENDED-RANGE PENICILLINS AMPICILLIN/AMOXICILLIN Uses In addition to streptococcal (including pneumococcal) strains, ampicillin and amoxicillin are also effective against many strains of Haemophilus influenzae, E. coli, Streptococcus faecalis and Salmonella. They are used for a variety of chest infections (e.g. bronchitis, pneumonia), otitis media, urinary tract infections, biliary infections and the prevention of bacterial endocarditis (amoxicillin). Amoxicillin is somewhat more potent than ampicillin, penetrates tissues better and is given three rather than four times daily. Both are susceptible to β-lactamases. Adverse effects Rashes are common and may appear after dosing has stopped. There is an especially high incidence in patients with infectious mononucleosis or lymphatic leukaemia. Pharmacokinetics The half-life of each drug is about 1.5 hours and they are predominantly renally excreted. CO-AMOXICLAV Co-amoxiclav is a combination of amoxicillin and clavulanic acid, a β-lactamase inhibitor. In addition to those bacteria that are susceptible to amoxicillin, most Staphylococcus aureus, 50% of E. coli, some Haemophilus influenzae strains and many Bacteroides and Klebsiella species are susceptible to co-amoxiclav. Adverse effects are similar to those of amoxicillin, but abdominal discomfort is more common. ANTIPSEUDOMONAL PENICILLINS Standard penicillins are not effective against Pseudomonas. This is not usually a problem, as these organisms seldom cause disease in otherwise healthy people. However, Pseudomonas infection is important in neutropenic patients (e.g. those undergoing cancer chemotherapy) and in patients with cystic fibrosis. Penicillins with activity against Pseudomonas have been developed and are particularly useful in these circumstances. These include piperacillin, azlocillin and ticarcillin. Uses These expensive intravenous penicillins are not used routinely. Their efficacy against Gram-positive organisms is variable and poor. They are useful against Gram-negative infections, particularly with Pseudomonas and they are also effective against many anaerobes. These drugs have a synergistic effect when combined with aminoglycosides in Pseudomonas septicaemias. Combinations of ticarcillin or of piperacillin with β-lactamase inhibitors designed to overcome the problem of β-lactamase formation by Pseudomonas are commercially available. Adverse effects These drugs predispose to superinfection. Rashes, sodium overload, thrombocytopenia and platelet dysfunction can occur.
Soliman s Auricular Therapy Textbook: New Localizations and Evidence Based Therapeutic Approaches was created ( M.D. Nader Soliman )
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Soliman s Auricular Therapy Textbook This textbook is considered the finest ever written in the field of auricular therapy. The auricular acupuncture microsystem is one of the most widely used special acupuncture techniques. This textbook is dedicated to teaching the sound foundations of this unique approach as introduced by its founder Dr. Paul Nogier of France. The scientific bases of the acupuncture microsystem with its three dime... Full description
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