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3.2. Identificación de dispositivos en el superflujo
General:Antibiotics of this group are:
(i) penicillins and (ii) semisynthetic derivatives of penicillin, and (iii) cephalosporins.
a. Structure These substances and their derivatives have a molecular structure based on a nucleus of two fused rings, one of which is the beta-lactam ring.
This structure is common to all antibiotics in this group.
b. Antibacterial activity Beta-lactam antibiotics act by inhibiting cell wall synthesis of susceptible bacteria.
They are effective mainly during the growth phase when cell walls are being synthesized.
c. Bacterial resistance The bacteria can develop enzymes known formerly, as, penicillinase. These enzymes can destroy the beta-lactam ring in the nucleus of penicillins and it’s derivatives thereby rendering
Table 9.4. Microorganisms commonly found and implicated in orofacial infections
Dental caries Periodontal disease Apical abscess Other diseases
Strep.mutans group Porphyromonas gingivalis Streptococci species A. israelii
crown caries adult periodontitis Strep. intermedius actinomycosis
Strep.salivarius rapidly progressing periodontitis Strep. angiosus C. albicans
root caries Prevotella intermedia Strep. constellatus candidosis
Actinomyces species adult periodontitis Bacteroides species root caries juvenile periodontitis
Lactobacilli acute necrotizing ulcerative gingivitis fissure caries severe gingivitis
Fusobacterium
acute necrotizing ulcerative gingivitis Actinobacillus actinomycetecomitans juvenile periodontitis rapidly progressing periodontitis Borrelia vicenti
periodontitis
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them ineffective. Cephalosporins are generally more resistant to the effect of beta-lactamases.
d. Toxic effects The principal adverse effect of penicillin is allergy. Allergy established to one type of penicillin is likely to cause similar reaction to other penicillins and it’s derivatives.
e. Excretion These antibiotics are excreted unchanged through kidneys.
Penicillins
Penicillin was discovered in 1929, however, the clinical trials were performed in 1940. It is derived from a mould, penicillin notatum. It was the first antibiotic drug to be used; and is still the best.
Classification
1. Naturally occurring penicillins: crystalline penicillin (penicillin G), phenoxymethyl penicillin (penicillin V)
2. Semisynthetic penicillins:
a. Short-acting, e.g. ampicillin, amoxycillin, amoxycillin with clavulanic acid, piperacillin and methacillin. They have special properties and uses. They are stable to gastric acids, make oral administration reliable and are resistant to beta-lactamase.
b. Long-acting, e.g. procaine penicillin, procaine penicillin fortified and benzathene penicillin.
Penicillin is linked with procaine to provide a sustained release preparation which gives an effective level of penicillin over a period of 24 hours.
Administrations
Route of administrations The oral route is the safest and the most frequently employed. In cases where the intramuscular injections are given in surgeries which are adequately equipped to deal with emergencies which may arise following such injections. In situations where IV administrations is indicated the patient should be hospitalized.
Subsequent to parenteral administrations, or doses in excess of one gram taken orally, the patients should be kept under observation for at least 30 minutes until it is established that no immediate side effects are likely to occur.
Broad spectrum with IV administration Administration of penicillins through IV route achieves much higher serum levels. The spectrum of bactericidal activity is much greater following IV use of penicillins; because of higher serum levels achieved.
Oral Administration
Since the levels of penicillin G achieved following oral administrations are not reliable, it is no longer adminis-tered by this route.
The semisynthetic penicillin that is phenoxymethyl-penicillin and ampicillin are well absorbed following oral administration. However, should be administered at least one hour before meals or three hours after meals to obtain maximum effect. Amoxycillin is well absorbed orally and can compete with food for absorption. It can be administered independently of food taken. The absorption of orally administered drugs is not reliable, following administrations of atropine or atropine-like substances used in dentistry, as premedications; for either sedation or general anaesthesia. Under such circumstances parenteral route should be employed.
Length of Course
Antibiotics once instituted, should be continued for at least 4 to 5 days to prevent reinfection/ recurrence of disease and to completely eradicate the disease.
Broad spectrum effect with clavulanic acid Clavulanic acid is derived from streptomyceclavuligerous. It acts by inhibiting beta-lactamase enzymes. The result of combining with amoxycillin is to broaden antibacterial spectrum of amoxycillin to include organisms that are resistant to amoxycillin because of their beta-lactamase production, e.g. species of staphylococci, nonhemolytic streptococci (including Strep.faecalis), and some Gram-negative bacteria like Haemophilus, E. coli, Klebsiella and Proteus species.
Measurements of Penicillin (Units and Micrograms)
A standard method of expressing the potency of penicillin was adopted in 1944 using crystalline sodium penicillin G as the standard. It is expressed in
‘International units’(iu).
250 mg penicillin equals approximately 4,00,000 iu.
Toxic Effects
Penicillin is remarkably free of toxic effects even in large doses administered over long periods. However, hypersensitivity reactions, in the form of allergy and anaphylaxis are reported. In case of allergy to one type of penicillin, there is likelihood that the person is allergic to other penicillins and in some cases to cephalosporins.
There is an inherent risk with all antibiotics of superinfection by a resistant organism. Allergy is the
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most common side effect of penicillin therapy. It may manifest in the form of skin rashes, dermatitis, serum sickness. These effects can be controlled by withdrawal of penicillin and use of antihistaminics.
Anaphylaxis
Anaphylaxis can occur and is a life-threatening situation. It is sudden in onset, characterized by coughing, tonic spasms, gasping, cyanosis, weak pulse and rapid drop in blood pressure.
Other Effects
Pregnancy The absolute safety of any of the penicillins or their semisynthetic derivatives taken during preg-nancy is not established. Penicillin should be employed only if there is an infection caused by a susceptible organism. The first choice is amoxycillin.
Lactation Penicillin appears in breast milk as similar levels to serum levels. Phenoxymethyl penicillin is preferable because of lower concentration in breast milk than serum.
Oral contraceptives Penicillin may render oral contra-ceptives ineffective. However, it has been reported that ampicillin did not reduce efficiency of oral contraceptives in the limited number of cases studied.
Cephalosporins
Cephalosporins have similar structure to penicillin but have a different source.
Mode of action They are bactericidal. They act by inhibiting the cell wall synthesis in growing bacteria.
They should not be used with other bacteristatic agents which inhibit protein synthesis such as tetracycline, erythromycin and lincomycin, etc.
Spectrum of activity They are effective against most species of staphylococci and streptococci except some species of Strep faecalis.
Indications Cephalosporins are bactericidal antibiotics and effective against most Gram-positive cocci, including most division III streptococci (enterococci) and most staphylococci. Cephalosporins provide an alternative drug in cases where penicillins are contraindicated.
Cephalosporins because they are bactericidal, may be used as an alternative drug to penicillin for prophylaxis against infective endocarditis.
Classification Cephalosporins are arbitrarily classified by generations; which is based on general features of spectrum of activity.
First generation Cephalosporins of this generation are effective against Gram-positive microorganisms, most Gram-positive cocci except enterococci. Methicillin resistant Staph. aureus and Staph. epidermidis. They are also active against E.coli, Klebsiella, Pneumonia and P. mirabilis. This generation of cephalosporins includes cephalothin and cephalexin.
Second generation This generation of cephalosporins has greater activity against Gram- positive microorganisms than first generation cephalosporins. This generation of cephalosporin includes cefotaxime.
Third generation These cephalosporins have less activity against Gram-positive organisms than first generation and more activity against Enterobacteriaceae, including beta-lactamase producing strains.
Erythromycin
1. Erythromycin is the principal member of macrolide group of antibiotics. Other macrolides currently available are azithromycin and roxithromycin, both are available for oral administration.
2. Erythromycin is a broad spectrum antibiotic. It is effective against most Gram-positive cocci, including many penicillinase- resistant strains of staphylococci and Staph. aureus, and many Gram-negative bacteria encountered in dental infections.
Preparation
It is available in forms of oral, IM or IV administrations.
Mode of Action
Erythromycin is generally considered to be a bacteri-static agent, though in some circumstances it has bactericidal effect. It acts by inhibition of protein synthesis.
Pharmacology
i. Oral preparation salts Erythromycin is available as stearate or estolate salt. The stearate salt is acid-labile, but less readily absorbed than the estolate form. The estolate form is well-absorbed, but in adults is associated with cholestatic hepatitis.
ii. Intramuscular preparations Erythromycin (base or plain) is utilized for intramuscular injections.
iii. Intravenous preparations Erythromycin lactobio-nate is used for intravenous administration slowly, in conjunction with intravenous infusion.
Absorption
Erythromycin is absorbed from upper part of small intestine. Food may delay absorption, and, it is
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mended that erythromycin be given one hour before meals.
Excretion
Erythromycin is excreted unchanged, in bile via liver.
Approximately, a quarter of the total dose is excreted through kidneys. Impaired liver, or to a lesser extent, impaired kidney function, could increase toxic effects of erythromycin. Hence patients with hepatic or renal dysfunction who are taking erythromycin should be observed for adverse effects.
Toxic Effects
Allergy to erythromycin is rare. Allergic reactions repor-ted are skin rash and other skin symptoms. Anaphy-laxis is reported.
Gastrointestinal effects These include nausea, vomiting and diarrhoea, etc.
Cholestatic hepatitis Erythromycin has been associated with cholestatic hepatitis in adults only. It is almost always related to the use of estolate forms.
Interactions
i. With antihistaminics and sympathomimetics Erythromycin in conjunction with astemizole causes increased levels of astemizole, leading to serious arrhythmias. Erythromycin , concurrently used with terfenadine may produce serious prolongation of QT interval (ECG). There is a potential for arrhythmia with sympathomimetic drugs. Hence such combinations are contraindi-cated.
ii. With theophylline Erythromycin when given with high doses of theophylline, may produce theophylline toxicity; including arrhythmias.
Further, theophylline may reduce the serum concentration of erythromycin to subtherapeutic levels.
iii. With carbamazepine Erythromycin when adminis-tered along with carbamazepine may increase the risk of carbamazepine toxicity.
iv. With warfarin Patients taking erythromycin and warfarin concurrently, there is increase in prothrombin time, leading to an increased risk of bleeding.
v. With benzodiazepines There is an increase in half-life of some benzodiazepines including midazo-lam and triazomidazo-lam.
vi. With oral contraceptives Erythromycin may affect the action of oral contraceptives.
Use during Pregnancy and Lactation
There are no teratogenic effects reported with the use of erythromycin. Erythromycin appears in breast milk.
No adverse effects have been reported on infants fed by mothers taking erythromycin.
Concomittant Use of Other Antibiotics
As the mechanism of action of erythromycin is different from that of penicillin and cephalosporins, these anti-biotics may be less effective when used together.
Lincomycin and clindamycin appear to compete with erythromycin, hence these antibiotics should not be used alongwith erythromycin.
Sulfonamides and Trimethoprim
Sulfonamides were first introduced in 1935. These agents are bacteristatic; and get inactivated by presence of pus. Sulfonamides act by inhibition of bacterial synthesis of folic acid from para-aminobenzoic acid (PABA).
Absorption, Distribution and Excretion
• Sulfonamides are well-absorbed after oral admini-stration and widely distributed through all body fluids.
• They cross placental barrier and also appear in breast milk.
• They are excreted through kidneys by glomerular filtration with preferential water reabsorption. The concentration of sulfonamides in urine is greater than that in blood. This leads to formation of crystals of sulfonamides; termed as crystalluria; and leads to renal damage. This can be avoided by excessive fluid intake and by administering substances which increase urine alkalinity.
Toxic Effects
Allergic reactions They include skin rashes, exfoliative dermatitis, S-J syndrome, polyarteritis nodosa and peri-pheral neuritis and photosensitivity.
Hemopoietic system Prolonged therapy can lead to macrocytic anaemia, due to inhibition of conversion of folic acid to folinic acid; rarely depression of bone marrow or selective blood dyscrasias like acute haemolytic anaemia, agranulocytosis and aplastic anaemia.
Renal damage Crystallization of sulfonamides may lead to renal damage. The signs include blood stained urine, renal pain and reduced urinary flow.
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Prolonged therapy should be accompanied by regular blood investigations including a differential white cell count.
Pregnancy and Lactation
Sulfonamides, including the combination with trime-thoprim may cause kernicterus by displacing bilirubin from plasma albumin in babies during their initial month of intrauterine life. Sulfonamides may cause increase in incidence of foetal malformations.
The drugs also are present in breast milk and may lead to diarrhoea, rash, jaundice, or kernicterus.
Sulfonamides or trimethoprim, or their combinations are not recommended for use in pregnancy or lactation.
Oral Contraceptives
Sulfonamides and trimethoprim may render oral contraceptives ineffective.
Sulfadiazine
It penetrates blood-brain barrier and achieves high levels in CSF. It is commonly used for prophylaxis to post-traumatic meningitis. A loading dose of 3 g is followed by 1 g, 6 hourly for 7 to 10 days. The drug can be administered by IV route; 1 g, 6 hourly. Caution should be exercised by taking a fluid intake of at least 2 liters/day to avoid crystalluria and renal damage.
Cotrimoxazole (Combination of Sulfamethoxazole and Trimethoprim)
This agent inhibits the conversion of folic to folinic acid which is important for bacterial synthesis of DNA and RNA. In this way, two bacteristatic agents join to form a bactericidal combination, cotrimoxazole (bactrim or septran).
Spectrum of activity It is active against Strep. pyogenes and most staphylococci and haemophili.
Indication Useful in acute exacerbation in post-irradiation osteomyelitis secondary to osteoradio-necrosis. It is also used in mixed actinomycotic infections along with penicillin.
Preparations It is available for oral administration.
Adult 80 mg of trimethoprim and 400 mg of sulfamethoxazole tablets are available. Two tablets are taken 12 hourly.
Child 20 and 100 mg respectively. The tablets can be dissolved in water; and, therefore, useful in patients with intermaxillary fixation.
Quinolones
Mechanism of Action
Inhibit synthesis of bacterial DNA.
Nalidixic Acid
Spectrum of activity It is effective against Gram-negative bacteria especially E. coli; Shigella and many strains of Proteus; and less effective against Aerobacter and Klebsiella species.
Absorption, distribution and excretion It is easily absorbed from gastrointestinal tract. It remains bound to plasma proteins; and excreted through kidney.
Adverse reactions Include nausea, vomiting and diarrhoea. Allergic reactions include pruritus, rash, urti-caria, fever, eosinophilia and photosensitivity. CNS manifestations include headache, malaise, drowsiness and myalgia. Overdosage may lead to convulsions in children.
Dosage It is available as 250 and 500 mg tablets and syrup. The dose is 4 g daily in 4 divided doses. It should not be prescribed in cases of cerebral arteriosclerosis, parkinsonism, impairment of hepatic and renal functions. It should be avoided during pregnancy and young children.
Fluoroquinolones
They are chemically related to nalidixic acid; and have fluorine in their chemical structure and hence the name.
The commonly used fluoroquinolones are: acrosoxacin, enoxacin, cinaxon, norfloxacin, ciprofloxacin, ofloxacin, pefloxacin, lomefloxacin and sparfloxacin.
Antibacterial spectrum They have broad spectrum of activity; and are bactericidal against most Gram-positive and Gram-negative organisms. It is effective against staphylococci including methicillin resistant Staph aureus (MRSA); and against streptococci including Strep pneumoniae. They have good activity against Enterobacteriaceae (E. coli, Klebsiella and Proteus mirabilis), including many organisms which are resis-tant to penicillins, cephalosporins and aminoglycosides.
Absorption, distribution and excretion They are adequately absorbed from gastrointestinal tract and distributed in body fluids. Most of them, except pefloxacin are excreted by kidney.
Therapeutic uses These drugs, except norfloxacin, are useful in treating systemic and serious infections.
Norfloxacin, because of it’s low serum levels is not
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useful in systemic infections; is effective in infections of urinary and gastrointestinal tracts.
Adverse reactions Generally, these drugs are well-tolerated.
1. GI tract toxicity includes nausea, vomiting, diarrhoea, anorexia and abdominal discomfort.
2. CNS toxicity includes confusion, nervousness, agitation and hallucinations.
3. Allergic reactions are rare.