By I. Knut. University of Minnesota-Morris.
Editorial comments • Amoxicillin–clavulanate is used for complicated or chronic sinusitis and otitis media because its spectrum includes S cheap 5mg provera with visa. It is the drug of choice for bite-related infections buy provera on line amex, as it provides coverage for oral anaerobes generic provera 5 mg with visa, streptococci, and Pasteurella multocida. Mechanism of action: Increases fungal cell membrane perme- ability causing cell death. Adverse reactions • Common: increased liver enzymes, tachycardia, azotemia, hypokalemia, hypotension, chills, fever, nausea, hyperbiliru- binemia. Clinically important drug interactions • Drugs that increase effects/toxicity of amphotericin B: amino- glycosides, cisplatin and other antineoplastic drugs, cyclosporine, corticosteroids, nephrotoxic drugs. Editorial comments • Currently two forms of amphotericin B are available on the market. While Ambisome is incorporated into a liposomal drug delivery system, Abelcet is combined with phospholipid. Fevers and chills have been reported to occur 1–2 hours after beginning intravenous infusion with Abelcet. Susceptible organisms in vivo: Streptococcus pneumoniae, beta- hemolytic streptococci, Enterococcus faecalis, viridans streptococci, Escherichia coli, Hemophilus influenzae, Neisseria gonorrhoeae, Proteus mirabilis, Salmonella (often resistant), Shigella (often resist- ant), Listeria monocytogenes, Neisseria meningitidis. Adjustment of dosage • Kidney disease: creatinine clearance <10 mL/min: increase dosing interval to 12 h. Consider skin testing, with major and minor antigenic components, of penicillin hypersensitivity in such patients to assess the possibility of a hypersensitivity reac- tion. If patient is given drug parenterally, observe for at least 20 minutes for possible anaphylactic reaction. Advice to patient • If you are receiving an oral contraceptive, use an alternative method of birth control. Clinically important drug interactions • Drug that increases effects/toxicity of penicillins: probenecid. Editorial comments • Ampicillin is added empirically for acute meningitis to cover for Listeria when the organism is a possible pathogen (neonate, adults >50 years, and immunocompromised patients). Adjustment of dosage • Kidney disease: creatinine clearance: 15–30 mL/min, dose every 12 hours; creatinine clearance: 5–14 mL/min, dose every 24 hours. Editorial comments • This antibiotic is used in mixed infections when Pseudomonas aeruginosa is not a pathogen. Onset of Action Peak Effect Duration 2–5 min 10 min 30 min–2h, depending on dose Pregnancy: Category C. Warnings/precautions • Use with caution in patients with the following conditions: atrial fibillation or flutter, hypertrophic obstructive cardiomyopathy. Clinically important drug interactions • Do not mix with furosemide; precipitate forms. While they enhance con- tractility and lower vascular resistance, they also have been associated with sudden death likely due to increasing meta- bolic demand. Amyl Nitrite Class of drug: Antianginal, nitrate vasodilator, antidote to cyanide poisoning. Mechanism of action: As antianginal agent, reduces peripheral resistance (arterial and venous) by vasodilation; decreases left ventricular pressure. As antidote for cyanide poisoning, pro- duces methemoglobin which binds and inactivates cyanide. If signs of poisoning reappear, administer 50% of initial dose of sodium nitrite and sodium thiosufate. Advice to patient: Advise patient that if pain is not relieved after 3 doses, call paramedics or to emergency room immediately. Mechanism of action: Competitive blocker of β-adrenergic receptors in heart and blood vessels. Adjustment of dosage • Kidney disease: creatinine clearance 15–35 mL/min: 50 mg/d; creatinine clearance <15 mL/min : 25 mg/d. If necessary to dis- continue, taper as follows: Reduce dose by 25–50% and reassess after 1–2 weeks. Advice to patient • Avoid driving and other activities requiring mental alertness or that are potentially dangerous until response to drug is known. Sit at the edge of the bed for several minutes before standing, and lie down if feeling faint or dizzy. Clinically important drug interactions • Drugs that increase effects/toxicity of β blockers: reserpine, bretylium, calcium channel blockers. If hypotension occurs despite correction of bradycardia, administer vasopressor (norephinephrine, dopamine, or dobutamine). Stop therapy and administer large doses of β-adrenergic bronchodilator, eg, albuterol, terbutaline, or aminophylline. Some advocate discontinuing the drug 48 hours before surgery; others recommend withdrawal for a considerably longer time. These drugs are also first choice for chronic stable angina, used in conjunction with nitroglycerin. Contraindications: Hypersensitivity to statins, active liver dis- ease or unexplained persistent elevations of serum transaminase, pregnancy, lactation. Warnings/precautions • Use with caution in patients with the following conditions: renal insufficiency, history of liver disease, alcohol abusers. Values should be obtained prior to and periodically after treat- ment begins to ascertain drug efficacy. It may be advisable to take a liver biopsy if transaminase elevation persists after drug is discontinued. Mechanism of action: Blocks nicotinic acetylcholine receptors at neuromuscular junction resulting in skeletal muscle relax- ation and paralysis. Editorial comments • This drug is not listed in Physician’s Desk Reference, 54th edi- tion, 2000. Mechanism of action: Blocks acetylcholine effects at mus- carinic receptors throughout the body. Adverse reactions • Common: Dry mouth, blurred vision (decreased accommodation), drowsiness, tachycardia, urinary hesitancy, dry skin, constipation. Parameters to monitor • Signs and symptoms of severe toxicity: tachycardia, supraven- tricular arrythmias, delirium, seizures, agitation, hyperthermia. Discontinue physostigmine if patient experiences dizziness, palpitations, rapid pulse. Editorial comments • This drug is not listed in the Physician’s Desk Reference, 54th edition, 2000. Mechanism of action: Inhibits phagocytosis, stabilizes lysoso- mal membranes, decreases rheumatoid factor levels.
Adverse Efects Ocular side-efects of mydriatcs and cycloplegics include transient stnging and raised intra-ocular pressure; on prolonged administraton purchase provera 5mg online, local irritaton order provera 10 mg with amex, hyperaemia discount provera 2.5 mg without a prescription, oedema and conjunctvits can occur. Contact dermatts can occur with the antmuscarinic mydriatc drugs, especially atropine. Systemic side-efects of atropine and cyclopentolate can occur in the young and the old; posterior synechia, headache, drowsiness, loss of taste, photophobia, brow ache, lacrimaton. Phenylephrine* Pregnancy Category-C Schedule H Indicatons Used in cough syrups, hypotension; mydriatc for eye conditons; uveits, wide angle glaucoma, refracton, ophthalmoscopic examinatons. Contraindicatons Hypertension (monitor blood pressure and rate of fow frequently); pregnancy (Appendix 7c); narrow angle glaucoma. Adverse Efects Headache, hypertension, bradycardia, arrhythmias, peripheral ischaemia. Treatment of anxiety should be limited to the lowest effective dose for the shortest possible time. The cause of insomnia should be established and appropriate treatment for underlying factors instituted before hypno- tics are considered. Tolerance and dependence (both physical and psychological) and subsequent difculty in withdrawing the drug may occur afer regular use for more than a few weeks. Patents with chronic anxiety, alcohol or drug dependence or those with personality disorders are more likely to become dependent. Anxiolytcs and hypnotcs should be prescribed in carefully individualized dosage and use should be limited to control of acute conditons such as panic atacks and acute anxiety and severe, incapacitatng insomnia. There is usually no justfca- ton for prolonging treatment with anxiolytcs and hypnotcs for more than one to two weeks. If used for longer periods, withdrawal should be gradual by reducton of the dose over a period of weeks or months, as abrupt discontnuaton may produce confusion, toxic psychosis, convulsions or a conditon resembling delirium tremens. The benzodiazepine withdrawal syndrome may develop at any tme up to 3 weeks afer stopping a long- actng benzodiazepine but may occur within a few hour in the case of a short-actng one. The syndrome is character- ized by insomnia, anxiety, loss of appette and body-weight, tremor, perspiraton, tnnitus and perceptual disturbances. These symptoms may be similar to the original complaint and encourage further prescribing. Patents should be warned that their ability to drive or operate machinery may be impaired and that the efects of alcohol may be enhanced. Contraindicatons Respiratory depression; marked neuromuscular respiratory weakness including unstable myasthenia gravis; acute pulmonary insufciency; sleep apnoea syndrome; severe hepatc impairment; not for chronic psychosis; should not be used alone in depression or in anxiety with depression; avoid injectons containing benzyl alcohol in neonates; narrow angle glaucoma, hypersensitvity. Precautons Respiratory disease; muscle weakness and myasthenia gravis; history of drug or alcohol abuse; marked personality disorder; pregnancy (Appendix 7c), lactaton; reduce dose in elderly and debilitated and in hepatc impairment, renal impairment; avoid prolonged use (and abrupt withdrawal thereafer); interactons (Appendix 6a); periodic blood count; liver functon test. Adverse Efects Drowsiness and lightheadedness on the next day; confusion and ataxia (especially in the elderly); amnesia; dependence; paradoxical increase in aggression; muscle weakness; occasionally: headache, vertgo, hypotension, salivaton changes, gastro-intestnal disturbances, visual disturbances, dysarthria, tremor, changes in libido, incontnence, urinary retenton; blood disorders and jaundice reported; skin reactons; rarely, apnoea and insomnia. Dose Oral Adult- Anxiety: 2 mg 3 tmes daily, increased if necessary to 15 to 30 mg daily in divided doses. Contraindicatons Respiratory depression; acute pulmonary insufciency; sleep apnoea; severe hepatc impairment; myasthenia gravis; hypersensitvity. Precautons Respiratory disease; muscle weakness; history of alcohol or drug abuse; marked personality disorder; lactaton (Appendix 7b); reduce dose in elderly or debilitated and in hepatc impairment (avoid if severe, Appendix 7a); renal impairment; avoid prolonged use and abrupt withdrawal; porphyria; interactons (Appendix 6a, 6c); pregnancy (Appendix 7c); liver functon test to be done, least amount of drug should be given in patents in whom depression accompanies anxiety and suicidal tendencies. May impair ability to perform skilled tasks, for example operatng machinery, driving. Adverse Efects Drowsiness and lightheadedness the next day; confusion and ataxia (especially in the elderly); amnesia; dependence; paradoxical increase in aggression; muscle weakness; occasionally headache, vertgo, salivaton changes, gastrointestnal disturbances, visual disturbances, dysarthria, tremor, changes in libido, incontnence, urinary retenton; blood disorders and jaundice; skin reactons; raised liver enzymes; reduces refexes; jaundice; psychological dependence; physiological dependence, respiratory arrest. Dose 2 to 6 mg/day given in divided doses, inital dose of 2 to 3 mg/day given twice or thrice a day. Contraindicatons Severe hepatc impairment; respiratory depression; acute narrow angle glaucoma; pregnancy (Appendix 7c), lactaton. Precautons Hepatc dysfuncton; impaired ability to drive or operate machinery; interactons (Appendix 6a). Nitrazepam Pregnancy Category-D Schedule H Indicatons Insomnia; epilepsy, vertgo, infantle spasm. Child Infantle spasm- 125 µg/kg twice daily, gradu- ally increase to 250-500 µg/kg twice daily. Contraindicatons Respiratory depression; marked neuromus- cular respiratory weakness including un- stable myasthenia gravis; acute pulmonary insufciency; severe hepatc impairment; sleep apnoea syndrome; not for use alone to treat depression (or anxiety associated with depression) or chronic psychosis. Adverse Efects Drowsiness and lightheadedness the next day; confusion and ataxia (especially in the elderly); amnesia may occur; dependence; aggression, anaphylaxis, dysarthria, blurred vision, slurred speech. Zolpidem Pregnancy Category-C Schedule H Indicatons Short term management of insomnia. Dose Adult- 10 mg immediately before bed tme, maximum 10 mg/day, controlled release tablets 12. Precautons Myasthenia gravis; depressed patents; hazardous occupatons requiring complete mental alertness or motor coordinaton such as operatng machinery or driving a motor vehicle; obstructve sleep apnoea, compromised respiratory functon; pregnancy (Appendix 7c), lactaton, interactons (Appendix 6a,6c). The response to antdepressant therapy is usually delayed with a lag-period of up to two weeks and at least six weeks before max. It is important to use doses that are sufciently high for efectve treatment, but not so high as to cause toxic efects. The use of more than one ant- depressant at a tme is not recommended since this does not enhance efectveness and it may result in enhanced adverse efects or interactons. Treatment should be contnued for at least 4 weeks (6 weeks in the elderly) before considering whether to change to another antdepressant due to lack of efcacy. In the case of a partal response, treatment may be contnued for a further 2 weeks (elderly patents may take longer to respond). Treatment at full therapeutc dose should be contnued for at least 4-6 months afer resolu- ton of symptoms (about 12 months in the elderly). Treatment should not be withdrawn prematurely otherwise symptoms are likely to recur. Patents with a history of recurrent depres- sion should contnue to receive maintenance treatment (for at least 5 years and possibly indefnitely). Reducton in dose should be gradually carried out over a period of about 4 weeks or longer if withdrawal symptoms emerge (6 months in patents who have been on long-term maintenance treatment). Tricyclic and related antdepressants can be divided into those with more or less sedatve efect. Those with sedatve propertes include amitriptyline and those with less sedatve efects include imipramine. These drugs are most efectve in the treatment of depression associated with psychomotor and physiological disturbances. Adverse efects include ant- cholinergic (more correctly antmuscarinic) symptoms of dry mouth, blurred vision, constpaton and urinary retenton. Minimal quanttes of tricyclic antdepressants should be prescribed at any one tme because they are dangerous in overdose. Amitriptyline* Pregnancy Category-C Schedule H Indicatons Moderate to severe depression, migraine prophylaxis; tension, headache, enuresis. Dose Oral Adult- Initally 75 mg (adolescents 30 to 75 mg) daily in divided doses or as a single dose at bed tme increased gradually as necessary to 150 to 200 mg daily.
The lipid core material consists of cholesterol and other lipids (cholesterol esters buy generic provera on-line, triacylglycerols and phospholipids) which are transported in plasma and other body fluids in the form of lipoproteins buy provera american express. These endogenous lipid carriers have been studied for the site-specific delivery of lipophilic drugs buy provera with amex. This system is being investigated for the targeting of hydrophobic antiviral prodrugs to parenchymal liver cells in viral hepatitis. This can be chemically cross-linked by the addition of a cross-linking agent such as glutaraldehyde or butadione, or thermally cross-linked by applying heat. The size of the particles is based on the droplet size of the initial emulsion, and can range from 15 nm–150 µm. The preparation, properties and degradation of these polymers have been discussed extensively in Chapter 4 (see Section 4. They are based on several different families of synthetic, non-ionic amphipatic molecules. At present, there is rather limited experience with niosomes as a parenteral delivery system and no clear advantages over liposomal systems have been established yet. The typical pharmaceutical considerations described above were not dealt with seriously in the early days of drug carrier research, thus early drug-carrier systems were associated with long gestation periods from product development to product marketing. The time-frame associated with the development of a drug targeting concept to a targeted drug product can be illustrated by the “liposome story”. Liposomes were originally used as biochemical tools for the study of cell membrane behaviour in the 1960s; the idea to use them as drug carriers was subsequently developed in the early 1970s. It took more than twenty years to develop the system from a concept to the first commercial parenteral liposome preparation carrying a drug (amphotericin B). Although this may seem 127 like quite a long gestational period, it must be remembered that liposomes were one of the first colloidal carrier systems designed for targeted drug delivery. Comparatively little was known about such systems and many technological and biopharmaceutical hurdles had to be overcome before marketing authorization for the first product could be obtained. Some of these hurdles encountered and solved over the years while developing liposomes as drug carriers include: • Poor quality of the raw material: In the early 1980s, the quality of lipids of several suppliers could vary considerably, both in quantitative and qualitative terms. Interestingly, over the years, the price per unit has dropped considerably while the quality has improved. Therefore a full physicochemical characterization of pharmaceutical liposomes is required in early stages of a development program (Table 5. In later development stages, these quality control assays can be used to obtain regulatory approval and to ensure batch-to-batch consistency. Biochemists, who worked with drug-loaded liposomes in the early days, had a completely different perception of “stability”, reproducibility, upscaling and toxicity than pharmaceutical scientists, who are familiar with the development of pharmaceutical formulations. For example, for a biochemist, a shelf life of a week at −70 °C may be acceptable, whereas a pharmaceutical product would be expected to have a minimum shelf-life of two years, preferably without refrigerator cooling. It took several years and considerable “mental adaptation” to bridge this cultural gap. Currently, quality is ensured by improved purification schemes, the introduction of validated analytical techniques and a better insight into lipid degradation mechanisms leading to better shelf-life conditions (Table 5. In addition, liposomal development has provided fundamental knowledge on the fate of particulate systems in vivo and how this fate can be manipulated for therapeutic gain. It should not exert side-effects, neither on its way to the therapeutic target, nor at the target site, nor during the clearance process. These systems have in common that they are indicated for the treatment of life-threatening diseases like cancer, and severe infectious diseases and, therefore, contribute considerably to our therapeutic armamentarium. It has become apparent that multidisciplinary approaches, employing the combined forces of such disciplines as molecular biology, biotechnology, pathology, pharmacology, immunology, pharmaceutical sciences, engineering, clinical sciences etc. In particular, insights into the anatomical, physiological and pathological constraints to the targeting concept have been growing fast over the past two decades. Moreover, progress in molecular biology and biotechnology allows the engineering of protein structures and their large-scale production, and will have a great impact on drug targeting concepts and the actual production of targeted drug delivery systems. In: Targeting of Drugs: Strategies for Stealth Therapeutic Systems (Gregoriadis, G. How can one realistically extend the blood circulation time of this particulate carrier system keeping in mind that this system should be used in patients? Both polymeric micelles and liposomes are being used as carrier systems for drugs. Human monoclonal antibodies are on the market both for therapeutic and diagnostic purposes. A hypothetical anti-leishmanial drug is strongly hydrophilic and positively charged at physiological pH. What targeting system would you recommend to develop if a fast market introduction is desirable? What is a prerequisite to use the concept of “macrophage mediated release of drugs” for therapeutic purposes? Moreover, the cost of oral therapy is generally much lower than that of parenteral therapy. Nevertheless, the oral route is not without disadvantages, particularly with respect to labile drugs such as peptide- and oligonucleotide-based pharmaceuticals. During the past two decades, numerous novel oral drug delivery systems, such as mucoadhesives, matrix systems, reservoir systems, microparticulates, and colon- specific drug delivery systems have been developed to overcome some of these limitations. It is appropriate to consider gastrointestinal structure in relation to gastrointestinal function. The function of the digestive system is to break down complex molecules, derived from ingested food, into simple ones for absorption into the blood or the lymph. This process occurs in five main phases, within defined regions of the gastrointestinal system: • ingestion (mouth); • fragmentation (mouth and stomach); • digestion (stomach and small intestine); • absorption (small and large intestine); • elimination of waste products (large intestine). There has recently been considerable interest in this site for the systemic delivery of drug moieties. The possibility of transmucosal delivery via the mucous membranes of the oral cavity is discussed in Chapter 7. The stomach The stomach is a sack that serves as a reservoir for food, where fragmentation is completed and digestion initiated. Digestion is the process by which food is progressively broken down by enzymes into molecules small enough to be absorbed; for example, ingested proteins are initially broken down into polypeptides, then further degraded into oligopeptides and finally into di- and tri-peptides and amino acids, which can be absorbed. Although the stomach does not contribute as much as the small intestine to the extent of drug 133 Figure 6. The small intestine The small intestine, comprising the duodenum, jejunum and ileum, is the principal site for the absorption of digestive products from the gastrointestinal tract. The first 25 cm of the small intestine is the duodenum, the main functions of which are to neutralize gastric acid and pepsin and to initiate further digestive processes. Digestive enzymes from the pancreas (which include trypsin, chymotrypsin, amylase and lipases) together with bile from the liver, enter the duodenum via the common bile duct at the ampulla of Vater (or hepatopancreatic ampulla). Bile contains excretory products of liver metabolism, some of which act as emulsifying agents necessary for fat digestion. The next segment of the small intestine, the jejunum, is where the major part of food absorption occurs. In addition to the great length of the small intestine, the available surface area is further enhanced by the presence of (Figure 6.
Advice to patient: Allow at least 1 hour between taking this medication and a bac- teriostatic antibiotic discount provera 2.5mg with visa, eg order provera 5mg otc, tetracycline or amphenicol discount 2.5mg provera fast delivery. Clinically important drug interactions • Drugs that decrease the effects/toxicity of ceftazidime: chlo- ramphenical. Editorial comments • Ceftazidime has excellent antipseudomonal activity (better than all other cephalosporins except for cefepime). Mechanism of action: Binds to penicillin-binding proteins and disrupts or inhibits bacterial cell wall synthesis. Adjustment of dosage • Kidney disease: Creatinine clearance <50 mL/min: 9 mg/kg or 500 mg q24h (normal dosing schedule); creatinine clearance 30–49 mL/min: 4. American Academy of Pedi- atrics considers cephalosporins to be compatible with breast- feeding. Contraindications: Hypersensitivity to other cephalosporins or related antibiotics, eg, penicillin. Mechanism of action: Binds to penicillin-binding proteins and disrupts or inhibits bacterial cell wall synthesis. American Academy of Pedi- atrics considers cephalosporins to be compatible with breast- feeding. Mechanism of action: Binds to penicillin-binding proteins and disrupts or inhibits bacterial cell wall synthesis. Susceptible organisms in vivo • Gram positive: excellent against streptococci and Streptococ- cus pneumoniae. American Academy of Pedi- atrics considers cephalosporins to be compatible with breast- feeding. Contraindications: Hypersensitivity to other cephalosporins or related antibiotics, eg, penicillin. Warnings/precautions • Use with caution in patients with the following conditions: kidney disease, penicillin allergy, elderly. For group A beta-hemolytic streptococcal infections, therapy should be continued for 10 days. Anegative response to penicillin does not preclude allergic reaction to a cephalosporin. Clinically important drug interactions • Drug that increases effects/toxicity of ceftriaxone: probenecid. Editorial comments • Uses for ceftriaxone are as follows: Acute bacterial meningitis: effective against Neisseria meningitidis, Hemophilus influenzae, and, most importantly, Streptococcus pneumoniae even when not susceptible to penicillin. Community-acquired pneumonia: effective against all important pathogens other than atypical organisms for which a macrolide or a quinolone is added (Legionella, Mycloplasma, Chlamydia). Mechanism of action: Binds to penicillin-binding proteins and disrupts or inhibits bacterial cell wall synthesis. Cefuroxime axetil tablets • Pharyngitis, tonsillitis Ð Adults, children >13 years: 250 mg q12h for 10 days. Cefuroxime suspension • Pharyngitis, tonsillitis Ð Children 3 months–12 years: 20 mg/kg/d in 2 divided doses. Adjustment of dosage • Kidney disease: Creatinine clearance <20 mL/min: 750 mg– 1. American Academy of Pedia- trics considers cephalosporins to be compatible with breastfee- ding. Contraindications: Hypersensitivity to other cephalosporins or related antibiotics, eg, penicillin. Warnings/precautions • Use with caution in patients with the following condition: kidney disease. For group A beta-hemolytic streptococcal infections, therapy should be continued for 10 days. A negative response to penicillin does not preclude allergic reaction to a cephalo- sporin. Advice to patient: Allow at least 1 hour between taking this medication and a bacteriostatic antibiotic, eg, tetracycline or amphenicol. Clinically important drug interactions • Drug that increases effects/toxicity of cefuroxime: probenecid. In children, however, ceftriaxone is superior to cefuroxime in the treatment of H. Advice to patient: Report to treating physician if you experience any of the following symptoms: dyspepsia, changes in stool, abdominal pain, swelling of ankles. Clinically important drug interactions • Drugs that increase effects/toxicity of celecoxib: rifampin, aspirin, fluconazole, inhibitors of cytochrome P450 2C9. Mechanism of action: Binds to penicillin-binding proteins and disrupts or inhibits bacterial cell wall synthesis. Susceptible organisms in vivo • Very active against Staphylococcus aureus and streptococci. Adjustment of dosage • Kidney disease: Creatinine clearance 50–80 mL/min: 2 g q6h; creatinine clearance 25–50 mL/min: 1. American Academy of Pedi- atrics considers cephalosporins to be compatible with breast- feeding. Contraindications: Hypersensitivity to other cephalosporins or related antibiotics, eg, penicillin. Warnings/precautions • Use with caution in patients with the following condition: kidney disease. For group A beta-hemolytic streptococcal infections, therapy should be continued for 10 days. Anegative response to peni- cillin does not preclude allergic reaction to a cephalosporin. Advice to patient: Allow at least 1 hour between taking this med- ication and a bacteriostatic antibiotic, eg, tetracycline or ampheni- col. Clinically important drug interactions: Probenecid increases effects/toxicity of cephalexin. Editorial comments • Oral cephalosporins are used for Staphylococcus aureus and streptococcal infection, when penicillins are to be avoided. They should not be used for sinusitis, otitis media, or lower respiratory infections because of poor coverage of Streptococcus pneumoniae, Moraxella catarrhalis, and Hemophilus influenzae. They are not suitable coverage for bite wounds as they do not cover Pasteurella multocida. Mechanism of action: Binds to penicillin-binding proteins and disrupts or inhibits bacterial cell wall synthesis. Susceptible organisms in vivo • Very effective against staphylococci and streptococci, poten- tially active against Streptococcus pneumoniae, active against enterococci. Adjustment of dosage • Kidney disease: Creatinine clearance less than 80 mL/min: usual adult dose; creatinine clearance 50–80 mL/min: ≤2 g q6h; creatinine clearance 25–50 mL/min: up to 1. American Academy of Pedi- atrics considers cephalosporins to be compatible with breast- feeding. Contraindications: Hypersensitivity to other cephalosporins or related antibiotics, eg, penicillin.