Posted in General Medicine for OMFS

Principles Of Antibiotics In Maxillofacial Surgery

Introduction

Beginning with the early work of Sir Alexander Flemming in 1929, when penicillin became the first “miracle drug”, innumerable lives been saved from such scourges as pneumonia, wound sepsis and bacterimia. Dentists benefited greatly from the discovery of penicillin, because of most odontogenic infections are caused by penicillin sensitive microorganisms.

These are the substances produced by microorganisms which suppress the growth of or kill the other microorganisms at very low concentrations.

Classification:

  1. A) Chemical structure:
  • Sulphonamides and related drugs – Sulfadiazine and others.

Sulfones – Dapsone (DDS), Para aminosalicylic acid (PAS).

  • Diaminopyrimidines – Trimethoprim, pyrimethamine.
  • B-lactam antibiotics – Penicillins, cephalosporins, monobacteriums, carbapenams.
  • Tetracyclines : Oxytetracycline, doxytetracycline etc.
  • Nitrobenzene derivatives: Chloramphenicol.
  • Aminoglycosides: Streptomycin, gentamycin, neomycin etc.
  • Macrolide: Erythromycin, oleandomycin, roxithromycin.
  • Nitrofuran derivatives: Nitrofurantoin, furazolidone.
  • Nitroimidazoles: Metronidazole, Tinidazole.
  • Quinolones: Nalidixic acid, norfloxacin, ciprofloxacin.
  • Nicotinic acid derivatives – Isoniazid, pyrizinamide, ethionamide.
  • Polyene antibiotics – Nystatin, amphotericin-B Hamycin.
  • Imidazole derivatives: Miconazole, ketoconazole, clotrimazole.
  • Others Rifampin, clindamycin, spectinomycin, vancomycin, lincomycin, sodium fluridate, cycloserine, viomycin, ethambutol, thiacetazone, clofazimine, griseofulvin.
  1. B) Mechanism of Action:
    1. Cell wall action – penicillin, caphalosporins, vancomycin.
    2. Protein synthesis interference – Erythromycin, chloramphenicol tetracycline.
    3. Detergent effect – Polymyxin, nystatin, amphotericin.
    4. Nucleic acid metabolism interference – Ciprofloxacin metronidazole.
    5. Intermediary metabolism – Trimethoprim, sulfonamides.
    6. C) Spectrum of activity:

Narrow spectrum – penicillin G, streptomycin and erythromycin.

Broad spectrum – Tetracyclines, chloramphenicol.

Extended spectrum – Penicillins, new cephalosporins, aminoglycoside.

  1. D) Type of organisms against which:
  1. Antibacterial – Penicillin, Aminoglycosides, erythromycin etc.
  2. Antifungal – Griseofulvin, amphotericin-B, Ketoconazole etc.
  3. Antiviral – Idoxuridine, acyclvir, amantadine, zidovudine etc.
  4. Antiprotozoal – Chloroquine, pyrimethamine, metronidazole, diloxanide etc.
  5. Antihelminthic – Mebendazole, piperazine, pyrantel, niclosamide etc.
  6. E) Type of action:

Bacteriostatic – Sulfonamides, tetracyclines, Chloromphenicol, Erythromycin, ethambutol.

Bactericidal – Penicillins, polypeptides, rifampin aminoglycosides, cotrimaxozole, cephalosporins, vancomycin, nalidixic acid, ciprofloxacin, isoniazid.

Some primarily static drugs may become cidal at higher concentrations.

  1. F) Source:

Fungi- Penicillin, cephalosporin, Griseofulvin.

Bacteria – Polymyxin B, Colistin, Bacitran, Tyrothricin Aztreonam.

Actinomycetes – Aminoglycosides, tetracyclines, chloramphenicol macrolides, polyenes.

Antibiotics useful for orofacial infections:

  • Penicillins
  • Clindamycin and Lincomycin.
  • Newer beta-lactum antibiotics
  • Carbapenems
  • Monobactams
  • Fluoro quinolones – ciprofloxacin.
  • Sulfonamides and trimethoprim.


Penicillins

Discovered in 1929, it was first antibiotic drug to be used.

Classification:

  1. Naturally occurring penicillins – penicillin G (t ½ 0.5hr), phenoxymethyl penicillin v. (t½ – 1hr) (0.1-3.0) MIC.
  2. Semisynthetic penicillins:
  3. Short acting – ampicillin (t ½ 0.7hr), amoxicillin, (1.0hr), amoxicillin with clavulanic acid, piperacillin and methicillin. They are stable to gastric acids and resistant to beta lactamase.
  4. Long acting – Procaine penicillin, procaine penicillin fortified and benzathine penicillin.

Penicillin is linked with procaine to provide a sustained release preparation which gives an effective level of penicillins over a period of 24 hours.

Route of administration:

Oral route is the safest and most frequently employed.

Broad spectrum I.V. administration. The spectrum of bacterial activity is much greater following IV use of penicillins because of higher serum levels achieved. The semisynthetic penicillins are well absorbed following oral administration.

Amoxycillin – Well absorbed orally.

Under GA or sedation or where atropine is used parental route should be employed.

Antibiotics should be continued for 4 to 5 days to prevent reinfection/ recurrence and to completely eradicate the disease.

Broad spectrum effect with clavulanic acid:

Clavulanic acid is derived from streptomycetclavuligerous. It acts by inhibiting beta lactamase enzymes. The result of combining with amoxicillin is to broaden antibacterial spectrum of amoxicillins to include organisms that are resistant to amoxicillin because of betalactamase production. Ex. Species of staphylococci, non-haemolytic streptococci (including strep faecalis) and some gram-ve bacteria like haemophilus, E.coli, klebsiela and proteus.

Adverse effects:

Hypersensitivity:

Anaphylaxis – Sudden onset, coughing, tonic spasms grasping, cyanosis, weak pulse and rapid drop in BP.

Allergy – Skin rashes, dermatitis, serum sickness, alteration of the efficacy of oral contraceptives.

Mechanism of action: Penicillin acts by interference of cell wall synthesis when bacteria divide in the presence of a beta-lactam antibiotics cell wall deficient forms are produced because the interior of bacterium is hyperosmotic, the CWD forms swell and burst leading to bacterial lysis.

Cephalosporins:

Similar structure to penicillin but have a difference source. Bactericidal MIC 2.8-8,

Indications:

Gram positive cocci (enterococci) and most staphylococci.

Alternate to penicillins.

Classification:

Ist Generation against gram positive

Gram +ve cocci except enterococci methicillin resistant staph aureus and straph epidermidis. Ecoli, Klebsilla, pneumonia and P.mirabilis.

Includes : Cephalothin ( t ½ 0.5) and cephalexin (t ½ 1.8hrs) cefazolin.

IInd  Generation of greater activity against gram +ve organisms to first generation cephalosporins includes cofaclor, cefuroxime.

IIIrd generation less activity against gram +ve than I generation drugs. More activity against enterobacteriacae including beta lactamase producing strains ceftriaxone, cefoperazone, cefotaxime.

Erythromycin: t ½ – 1.5 hrs; MIC 0.1-1:

Macrolide group of antibiotics. Bacteriostatic other macrolides are azithromycin and roxithromycin. Effective against – Gram +ve cocci including many penicillin resistant strains of staphylococcus and staph aureus, and many gram –ve bacteria in dental infections.

It is bacteriocidal in few circumferences.

It should be administered one hour before meal coz food may alter the absorption.

It is excreted unchanged via liver and partly kidneys.

Mechanism of action:

Acts by inhibiting protein synthesis. Combines with ribosomes and interferes with translocation. It suppresses the synthesis of larger proteins.

Toxic effects – Allergy – rare anaphyllaxis.

Nausea, vomiting, diarrhoea etc.

Cholestatic hepatitis – related to the use of estolate forms.

Interactions:

  1. With antihistamines and sympathomimetics. When used in conjunction with astemizole leads to increased levels of astemizole leading to serious arythmias. When used with terfenadine – potential for arythemias.
  2. With theophyline – Erythromycin when given in high concentrations of theophylline may produce theophylline toxicity including arythmias.
  • With carbamazapine – carbamazapine toxicity.
  1. With warfarin – increased prothrombin time and increased risk of bleeding.
  2. With benzodiazepines – increases the half life of benzodiazepines (midazolam and triazolam).
  3. With oral contraceptives – Alters the actions.

They are less effective when used with penicillins and cephalosporins, lincomycin and clindamycin should not be used along with erythromycin.

  1. Lincomycin and clindamycin (t ½ 2.7 hr) MIC 0.1-3.1:

Lincomycin is reserved for parenteral administration and clindamycin is more active and has less side effects as for oral administrations. They are bacteriostatic acting by inhibiting protein synthesis. They are effective against most gram+ve and many gram-ve bacteria including bacteriodes, anaerobic streptococci and clostridia.

They are very effective in bone infections and form a second line of treatment is osteomyelitis.

Mechanism of action – Similar to erythromycin i.e. inhibits protein synthesis by binding to ribosomes and interferes the translocation.

Toxic effects: Nausea, vomiting, diarrhea, candidaisis may occur and neither antibiotic may be used in presence of candida infections.

Neutropenia, leucopenia, agranulocytosis and thrombocytopenic purpura, pseudomembraneous colitis characterized by diarrhea, abdominal pain, fever and blood and mucus faeces.

  1. Metronidazole (t ½ 4.0hr) MIC<3.0:

Effective in anaerobic infections and ANUG. It is used with one of the penicillins to treat orofacial infections. It can also be used with cephalosporins in penicillin allergic patients.

It is effective against gram +ve and –ve bacteria including bacteriodes, clostridia and spirochetes.

It is absorbed from GIT and competes with food. It is excreted in urine which may be coloured red brown. Impaired renal and hepatic function can prolong presence of drug in serum. Also excreted in saliva and breast milk in similar concentration to plasma.

Toxic effects:

Teratogenic effects are possible:

Blood dyscrasias, if therapy exceed ten days. It will affect patients with CNS pathology such as depression or psychosis.

Convulsions, dizziness, vestibular symptoms, hypotension and hallucinations.

It is contraindicated in patients taking phenytoin. It may enhance the effects of warfarin and prolong coagulation time.

Mechanism of action : It enters the microorganisms by diffusion, gets reduced to intermediate compounds which causes cytotoxicity by damaging DNA. It also inhibit cell mediated immunity to induce mutagenesis and cause radiosensitization.

  1. Aminoglycosides: MIC 0.1-3.0

Includes gentamycin, vancomycin, streptomycin, kanamycin, neomycin and tobramycin. These are bactericidal and effective against many gram negative bacteria, especially those resistant to penicillins. These are potentially toxic and are administered parenterally. These drugs are used in treatment and prevention of severe infections. They act by inhibition of protein synthesis.

Mechanism of action: They combine with ribosomes and induce misreading of mRNA codons: one or more wrong aminoacids are entered in the peptide chains. When exposed to these drugs, sensitive bacteria becomes more permeable ions aminoacids and even proteins leak out, followed by cell-death.


Gentamicin (t ½ 2.0 hrs):

Administered IM as there is a better control on absorption and avoids high serum concentration. It is effective against gram positive and negative bacteria including penicillinase resistant staphylococci. The combined effects of ampicillins and gentamicin are effective against a wide spectrum of gram +ve bacteria including streptococci and staphylococci and gram-ve bacteria. Gentamicin and ampicillin should be administered separately coz gentamicin gets destroyed.

It is indicated in severe anaerobic infections.

Dose –        Adult – 3-7mg/kg/day in 2-3 divided dose.

Child – 1-3mg/kg/day in 2-3 divided dose.

Toxicity – It causes ototoxicity (vestibular and cochlear). If serum concentrations exceeds 10mg/ml transient tinnitus may occur.

When used over a weak, nephrotoxicity occurs.

Allergic reactions – not recommended in lactating mothers.

Vancomycin (t ½ 6 hours)

It has similar properties to gentamicin.

Indications – Severe orofacial infections.

Patients allergic to penicillins.

Patients with risk for endocarditis.

 

Dose:

Adult IV 500mg (IV infusion) 6th hourly or 1gm 12th hourly.

Child – 44mg/kg/day in divided doses.

Adverse reactions – Anaphyllaxis, deafness, tinnitus, hypotension and irritation at the site of injection.

Rapid administration may lead to pruritis, generalized flushing and erythrematous macular rashes and superficial thrombophlebitis.

Fluoroquinolones:

They are chemically related to nalidixic acid and have fluorine in their chemical structure and hence the name.

Commonly used fluoroquinolones are: Acrosaxacin, enoxacin, cinaxon, norfloxacin, ciprofloxacin (t ½ 3.3hrs), ofloxacin pefloxacin, lomefloxacin and sparfloxacin.

They have broad spectrum activity and bactericidal against most gram +ve and –ve organisms. Effective against staphylococci including methicillin resistant staph aureus and against streptococci including strep pneumonia. They have good activity against enterobactericae (E. coli, Klebsilla and proteus mirabilis) including many organisms which are resistant to penicillins, cephalosporins and aminoglycoside.

They are absorbed from GIT and distributed in body fluids. Most of them except pefloxacin are excreted by kidney.

These drugs except norfloxacin are useful in treating systemic and serious infections. Norfloxacin, because of low serum levels it is not effective in systemic infections, it is much effective in urinary and GIT infections.

Mechanism of action: They are bactericidal, they inhibit bacterial DNA gyrase, an enzyme which nicks double stranded DNA. The DNA gyrase reseals the nicked ends of DNA during replication or transcription.

Adverse reactions: GIT, Nausea, vomiting, diarrhea, anorexia, and abdominal discomfort CNS Toxicity – confusion nervousness, agitation and hallucinations. Allergic reactions are rare

Sulfonamides and trimethoprim:

These agents are bacteriostatic and gets inactivated by presence of pus. They act by inhibition of bacterial synthesis of folic acid from paraamino benzoic acid (PABA).

They are well absorbed by oral administration and widely distributed through all body fluids. They cross placental barriers.

They are excreted through kidneys by glomexular filtration with preferential water reabsorption. The concentration of sulfonamides in the urine is greater than in blood this leads to formation of crystals of sulfonamides termed as crystalluria and leads to renal damage. This is avoided by excessive fluid intake and by administering substances which increase urine alkalinity.

Toxic effects:

Allergic reactions – Skin rashes, exfoliative dermatitis, S-J syndrome, polyarteritis nodosa – and peripheral neuritis and photosensitivity.

Prolonged therapy can lead to macrocytic anorexia due to inhibition of conversions of folic acid to folinic acid; rarely depression of bone marrow or selective blood dyscrasias like acute hemolytic anaemia, agranulocytosis and aplastic anaemia.

Renal damage

They may also cause kernicterus by displacing bilirubin from plasma albumin in babies during intrauterine life. They may also cause foetal malformation.

These drugs present in breast milk may lead to diarrhea, rash, jaundice or kernicterus. They may also alter the actions of oral contraceptives.

Sulfadizine: It penetrates blood brains barrier. It is commonly used in traumatic meningitis.


Contrimoxazole (Sulfamethoxazole and Trimethoprim) t ½ 10-hrs

This agent inhibits the conversion of folic acid to folinic acid which is important for bacterial synthesis of DNA and RNA.

It is active against strep pyogens and most staphylococci and haemophili.

It is indicated in acute exacerbations in postirradiation osteomyelitis secondary to osteoradionecrosis. It is also used in mixed actinomycotic infections along with penicillin.

Dose 80mg of Trimethoprim + 400mg of sulfamethoxazole 2 tabs 12 hrly. Child 20mg + 100mg.

Mechanism of actions of sulfanamides:

Sulfanomides being structural analogues of PABA inhibit bacterial folate synthetase. Also being chemically similar they themselves get incorporated to form an altered folate which is metabolically injurious.


PRINCIPLES OF ANTIBIOTIC THERAPY

Principles of appropriate antibiotic use:

Several principles are to discussed that would serve as guidelines in making a decision to give an antibiotic.

  • Presence of infection: In most clinical situations, it is easy to determine if a patient has an infection. The clinical signs and symptoms of infections are pain, swelling, surface erythema, pus formation and limitation of motion. Systemically fever, lymphadenopathy, malaise, a toxic appearance and an elevated WBC counts are found, oral surgeons frequently face patients with some of the signs of infection such a situation occurs with a patient with a painful tooth but has no swelling or other signs of infection. It could be just an inflammatory condition like pulpitis, rather than an infection. In such conditions antibiotic therapy stands inappropriate.

In some patients pain and swelling observed postoperatively after a surgical removal of third molars or extensive maxillofacial surgery, the signs and symptoms of infections may not be elicited completely, it could be because of the surgery.

When a patient operated under GA develops pain and swelling along with fever but without the other signs of infection, may be because of surgical stress. Fever could be in result of insufficient postoperative pulmonary care.

Thus the diagnosis of infection and the clinicians judgement should be based on a logical process of elimination.

  • State of host defense : Host defense mechanisms are the most important factors in the final outcome of a bacterial insult. The inflammatory response and production of antibiotics provides most of this protection. If this mechanism or other host defenses are impaired, infections may result. Thus when forced with the issue of prophylactic therapy of infection, the surgeon must evaluate the general state of the host defense mechanisms.

Antibiotics help in situations in which the host has been overwhelmed by bacteria or when especially virulent bacteria are involved when defense mechanism are impaired antibiotics play a more important role in the control of infection.

The causes of depressed defenses can be divided into four categories.

Physiologic, disease related, defective immune system related and drug suppression related (anticancer drugs).

When dealing with an established infections in patients who fit into any of these categories, aggressive antibiotic therapy should be employed. Bactericidal rather than bacteriostatic antibiotics should be used.

When surgery is required in any compromised host antibiotic prophylaxis of wound infection must be considered.

  • Surgical drainage and incision:

Surgical intervention is necessary in both chronic abscess and acute indurated cellulitis. Many infections demonstrate both abscess formation and indurated cellulitis. In such situations incision and drainage of the abscess result in reduction of pressure in the area of cellulitis. It may also obviate the use of an antibiotic or may increase the effectiveness of an antibiotic as the vascular flow is restored. The host defense mechanisms are also restored with the incision and drainage.

  • The decision to use antibiotic therapy:

When the clinician is confronted with a patient with a possible infection, each of the proceeding factors must be weighed carefully. Only this can an appropriate decision be made about whether antibiotic therapy is necessary.

Minor infections in patients with depressed host defenses must be treated aggressively with antibiotics and surgery as early as possible (bactericidal) surgical intervention of the moderate or severe infections is much important along with or without use of antibiotics.

In some case like minor infections or moderate infections, where the host defense is intact surgical drainage will be sufficient without the use of antibiotics (controversial).

Principles for choosing the appropriate antibiotic:

Once the decision has made to use antibiotics as an adjunct to treating as infection, the antibiotic should be properly selected. The following guidelines are useful in making this decision.

  1. Identification of the causative organism:

The identity of a pathogen may be scientifically determined either in the laboratory, where the organism can be isolated from pus, blood or tissue or empirically based upon the knowledge of the pathogens and clinical presentation of specific infection. Antibiotic therapy is then either initial or definitive depending upon whether or not the organism is diagnosed precisely.

Initial empirical therapy can be instituted if the following criteria are met:

  • The site and feature of the infection have been well defined.
  • The circumstances leading to the infection are well known.
  • Organisms that most commonly cause such infections.

The typical odontogenic infections are caused by a mix of both aerobic and anaerobic, bacteria. About 70% of these infections are caused by this mixed flora.

Pure anaerobic infections are seen in only 25% of odontogenic infections.

Bacteria found in the well circumscribed chronic non-advancing abscess are almost always anaerobic bacteria. In cellulitis type infections aerobic bacteria is the shown cause. As the infection becomes more severe the microbiology becomes a mixed flora of aerobic and anaerobic bacteria. If the infection process subsides and controlled by the body’s defense mechanisms, the aerobic bacteria no longer survives due to hypoxic and acidotic environment.

The aerobic bacteria found in odontogenic infections are primarily gram positive cocci most of which are viridans type of streptococci. They account for approximately 85% of the aerobic bacteria found in odontogenic infections. These organisms are susceptible to penicillins and other antibiotics with an antimicrobial spectrum similar to that of penicillins.

Anaerobic bacteria, gram +ve cocci is seen in approximately 1/3rd of all odontogenic infections and other gram –ve rods are seen in 50% of odontogenic infections. The main species of the gram positive cocci are strep intermedius and peptostreptococcus species. The main gram –ve rods are porphynomonas, prevotella and fusobacterium. The fusobacterium species appear to be the most virulent and when in conjunction with strep milleri, are associated with the most aggressive odontogenic infections.

In mixed odontogenic infections

Early cellulitis is caused by streptococcus and chronic abscess is caused primarily by anerobic bacteria only. Hence the antibiotic useful for odontogenic infections must be effective against streptococcus and against anaerobes. In the later stage chronic abscess situation, anti anaerobic activity is the major antibiotic goal.

Culture should be performed in situations like compromised host defenses, patients received antibiotics for 3 days but no improvement, postoperative wound infection, recurrent infection, suspected actinomycosis and osteomyelitis. More precise information about the bacteria must be available for adequate treatment.

  1. Determination of the antibiotic sensitivity:

When treating an infection that has not responded to initial antibiotic therapy or when treating a postoperative wound infection, the causative organism must be precisely identified and the antibiotic sensitivity must be determined.

Most odontogenic infections are caused by streptococci which do not vary much in antibiotic sensitivity patterns. Staphylococcus must be treated with susceptibility information. Penicillin G can be used only if sensitivity studies supports its effectiveness, otherwise penicillanase resistant penicillins should be used. Recent reports indicate that about 20% of B.melaninogenesis is resistant to penicillins.

Penicillin is excellent for streptococcus and major anaerobes:

Erythromycin is very effective against streptococcus, peptostreptococcus and fusobacterium, clindamycin is very good for streptococcus and for the five major anaerobic groups.

Cephalexin is only moderately active against streptococcus and is good against five groups of anaerobes. Metronidazole has no activity against streptococcus but has excellent activity against the five anaerobic groups.

Several tests should be performed to provide information about the plasma level necessary to kill or inhibit growth of a bacteria by disclosing the minimal inhibitory concentration (MIC) of a specific antibiotic for the specific organisms.

  1. Use of a specific, narrow-spectrum antibiotic / selection should be based on consideration of several factors. The antibiotic with the narrowest spectrum should be choosen because if broad spectrum antibiotic is used then they might lead to resistance of other bacteria which are not involved in the infection.

The use of narrow spectrum antibiotics also minimizes the risk of superinfections.

  1. Use of the least toxic antibiotic: Select the least toxic drug from among those that are effective.

Antibiotics are used to kill living bacteria, but some antibiotics also kill or injure human cells, thus they can be highly toxic. The clinician should continuously be alert for signs of toxicity and also instruct the patient to look for and report them as well.

  1. Patients drug history:

Review of previous allergic reactions and previous toxic reactions should be done. Patients who have a history of previous major toxic or minor side effects from an antibiotic are likely to experience the same problem again. Attempts should be made to identify the drug and the precise reactions. An alternative drug should be used if possible, potential interactions with other drugs that the patient intaking must be considered. Antibiotics may prolong enhance or interface with the other medications that the patient is taking.

  1. Use of a bactericidal rather than a bacteriostatic drug:

Antibacterial therapy reduces the bacterial challenge and allows host defenses to complete the treatment.

Bactericidal is the most preferred one because of the following advantages:

  1. There is less reliance on host resistance.
  2. The antibiotic itself kills the bacteria.
  3. The drug works faster than bacteriostatic drugs.
  4. There is greater flexibility with dosage intervals.

The bacteriostatic drug exert their influence only when present in the patients tissues. Thus the bacteria resumes normal growth after the drug is eliminated.

  1. Use of antibiotic with a proven history of success:

The best evaluation of the efficacy of a drug in a particular situation is the critical observation of its clinical effectiveness over a prolonged period of time. This helps in the assessment of the frequency of treatment success and failure, the frequency of adverse reactions and the side effects. By such observations, a few drugs become standardized for use and should not be put aside for an unproven drug without good reasons.

Also, with increasing exposure, initially sensitive bacteria become more resistant to the antibiotics being used. This development of resistance to an antibiotic may be slowed by limiting its use on it may be hastened by its wide use.

Newer antibiotics should be used only when they offer clear advantages over older ones. They may be effective for bacteria against which no other antibiotic is effective, as was the case when methicilin became available for penicillinase producing staphylococcus. In such a situation, that antibiotic must be reserved for those patients with infections caused by bacteria that have a proven sensitivity to that antibiotic.

Additionally a new antibiotic may be more active at lower concentrations (thus reducing cost and dose related toxicity reactions).

  1. Cost of antibiotics: The use of a drug should always consider the patients compliance and maximum effectiveness.

PRINCIPLES OF ANTIBIOTIC ADMINISTRATION

  1. Proper dose:

The goal of any drug therapy should be to prescribe or administer sufficient amounts to achieve the desired therapeutic effect, but not enough to cause injury to the host.

The laboratory studies play an important role in helping the clinicians decision on the dose.

Determination of MIC (minimum inhibitory concentration) of an antibiotic should be done. For therapeutic concentrations the MIC of an antibiotic at the site of infection should be three to four times the MIC.

Therapeutic levels greater than 3-4 times MIC generally do not improve the therapeutic levels but rather causes likelihood to toxicity.

In situations in which the site of infection may be isolated from the blood supply as in abscess formation or in non-vital tissue, increased doses may be justified than high plasma concentrations may allow a greater amount of antibiotic to reach the sealed off bacteria by diffusion. In these cases surgical interventions must be implicated. Sufficient antibiotic must be given to reach the therapeutic levels cause the subtherapeutic levels may mask the infection and suppress the clinical manifestations without killing the bacteria and can lead to recurrence of the infection once the drug is eliminated.

  1. Proper time interval:

Just as there is a usual recommended dose of antibiotic, there is a usual recommended dosage interval, knowledge of pharmacokinetics of the drug is important.

Each antibiotic has an established half life, during which one half of the absorbed dose is excreted. The usual dosage interval for the therapeutic use of antibiotics is four times the T ½. At five times the T ½, 95% of the drug is excreted. Ex: the T ½ for cefazolin is almost 2 hours. Thus the time interval between doses should be 8 hours.

Most antibiotics are eliminated via the kidneys, the patients with pre-existing renal disease and subsequent decreased clearance may require longer intervals between doses to avoid overdosing, to maintain usual dosage schedule, excessive plasma levels and toxicity.

  1. Proper route of administration:

In some infections only parenteral administration produces the necessary serum level of antibiotic. The oral results in the most variable absorption. Most antibiotics should be taken in the fasting state to ensure maximum absorption.

In long term parenteral administration is necessary. Repeated IM is poorly accepted in patients in such situations IV is the best rate to administer.

The parenteral administration should not be changed to oral for atleast 5 to 6 days (i.e. till we get the maximum therapeutic blood levels). In mild infections it can be changed after 2-3 days.

  1. Combination antibiotic therapy:

In addition to treating infections with the most specific antibiotics possible and avoiding broad spectrum antibiotics, combination drug therapy should also be avoided. They might result in the depression of the normal host flora and increase opportunity for resistant bacteria to emerge. For routine infections, the disadvantage of combination therapy outweigh the advantages.

 

It is indicated in few situations like in:

  1. Situations of life threatening situations of unknown cause.
  2. To increase the bactericidal effect of a specific organism.
  3. Prevention of the rapid emergence of resistant bacteria.
  4. Empiric therapy of certain odontogenic infections like when the infection progresses to the lateral and retropharyngeal spaces and caused by aerobes and anaerobes.

Monitoring the patient:

Monitoring related specifically to the antibiotic therapy should be directed at the response to treatment and at the development of adverse reaction.

  1. Response to treatment:

The response to antibiotic therapy results begun by the second day and initially it is a subjective sense of feeling better. The objective signs of improvement occur with the decrease in temperature, swelling, pain and lessening of the trismus. At such time decision to be taken about the duration of antibiotic therapy. Ideally antibiotic should be given until offending bacteria is eradicated. If this is not done then there could be chance of recurrence. Careful revaluation should be done if the patient is not showing the signs of improvement special attention should be given to opt for surgical intervention. If the initial therapy fails several factors should be considered:

  1. Route of administration.
  2. Patient compliance.
  3. Correct antibiotic.

Causes of failure in treatment of infection:

  1. Inadequate surgical treatment.
  2. Depressed host defences.
  3. Presence of foreign body.
  4. Antibiotic problems – Drugs not reaching infection.

Dose not adequate

Wrong bacterial diagnosis.

Wrong antibiotic.

  1. Development of adverse reactions:

Adverse reactions occur all too commonly. Almost 15 to 20% of hospitalized patients experience adverse reactions. Hypersensitivity occurs with all antibiotics. Most common with penicillins and the cephalosporins. They manifest as accelerated anaphylactic (Type I) reactions or less severe reactions associated with edema, urticaria, itching, or they may be delayed reactions presenting only as a low grade fever. Diagnosis of anaphylaxis is not difficult but treatment must be rapid and intense.

To prevent toxicity it is important to avoid excessive dose. Therapeutic levels must be reached, but the higher the level the more likely a toxic reaction.

One toxic reaction should be discussed specifically, the problem of antibiotic associated colitis (AAC). AAC was originally associated with clindamycin therapy but has now been recognized to be caused by almost every antibiotic with the exception of the aminoglycoside. The 3 most common drugs that lead to AAL are clindamycin, ampicillin-amoxycillin and the cephalosporins. The pseudomembranous colitis is caused by toxins from clostridium difficile. Patients receiving antibiotics that alter colonic flora may have an overgrowth features of AAC. Clinical features of AAC – profuse watery diarrhea that may be bloody, crampes on abdomen, pain, fever and leukocytoss. Treatment is discontinue the antibiotics and administer anticlostridial antibiotic like vancomycin.

  1. Superinfection and recurrent infection:

The normal flora as a defense mechanism against infection, but when the flora is altered or eliminated by an antibiotic, the pathogenic bacteria resistant to the antibiotic may cause secondary infection or superinfection.

A common secondary infection in the oral cavity is candidiasis, which is primarily the result of use of penicillins. Secondary pneumonia is seen in hospital in patients who are on the broad spectrum antibiotics. Regular followup of the patient is necessary to monitor the reinfection or recurrence.

Principles of Therapeutic uses of antibiotics in maxillofacial surgery:

Maxillofacial surgeons frequently must use antibiotics in the treatment of their patients. By keeping in mind the previously discussed principles, they will be able to select those situations in which antibiotic therapy is indicated and there in which it is not.

As a general guidelines, antibiotic therapy should be reserved for those patients with clearly established manifestations of infection, that is fever, malaise, swelling and pain. Such patient should be treated surgically as early as possible.

Abscess – Surgical interventions and antibiotics.

Pericoronitis – Preoperative antibiotics and surgery and postoperative antibiotics.

Osteomyelitis – Preoperative antibiotics and surgery nd postoperative antibiotics.

Fractures – Immediate preoperative antibiotics and surgery and postoperative antibiotics.

Soft tissue wounds – Debridement and toileting later antibiotics.

Principles of Prophylactic antibiotics:

The use of antibiotics for prevention of infection is clearly established and it not accepted widely.

Infection prophylaxis obviously has many advantages:

  1. Prevention of infection.
  2. Decrease patient morbidity and mortality.
  3. Decrease hospital stay.
  4. Decreased medical cost.
  5. Decreased total antibiotic usage.
  6. Decrease numbers of resistant bacteria – because of short term course.

Disadvantages:

  1. No reduction of infection.
  2. Development of increased number of resistant bacteria.
  3. Delay in onset of infection.
  4. Adverse effect on surgical technique.

The most effective method which can be practiced is a “short term administrations of a narrow spectrum antibiotics”.

In order for prophylaxis antibiotics to be effective a set of well established guidelines must be followed. The principles for prophyllactive antibiotics are:

  1. The operative procedure must have a risk of significant bacteria contamination and a high incidence of infection.
  2. The organism most likely to cause the infection must be known.
  3. The antibiotic susceptibility of the causative organism must be known.
  4. To be effective and to minimize adverse effects the antibiotic must be in the tissue at the time of contamination (operation) and it must be continued for not more than 4 hours after cessation of contamination.
  5. The drug must be given in dosages sufficient to reach four times the MIC of the causative organisms.
  6. Time the antibiotic correctly.
  7. Use the shortest effective antibiotic exposure.
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Author:

I am a practicing maxillofacial surgeon working in India.

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