ANTIBIOTICS IN ORAL AND MAXILLOFACIAL SURGERY
AIM: The aim of this seminar is to discuss various antibiotics and their use in oral and maxillofacial surgery.
INTRODUCTION: Antibiotics are regarded as miracle drugs. They are our most effective weapons against infectious diseases brought about by microorganisms like bacteria, fungi and parasites. In the past treating the bacterial infections was very difficult. In fact before the discovery of antibiotics, many patients contracting bacterial infections never made it out of hospital beds alive. This is why discovery of antibiotics was one of the most important health advances in human history. Antibiotics have a well documented efficacy in the trearment of established infections and as prophylactic agents in medically compromised patients. DEFINITION: Antibiotic is a chemical substance produced from microorganisms have the property of inhibiting the growth of other microorganismsin high dilution. HISTORY: PAUL ERHLICH(1854-1915) an organic chemist observed that methylene blue specifically killed and stained certain bacterial cells and reasoned that chemical might be produced that could unite with and destroy parasitic agents of disease without injuring the host cells. First accidentally discovered in 1928 by ALEXANDER FLEMING when a dish in which he was growing staphylococcus bacteria became contaminated with pencillium mould was destroying bacteria. This substance was later named PENICILLIN. In 1944 WALKSMAN isolated streptomycin from streptomyces griseus in culture from chicken throat. MODE OF ACTION: Antibiotics act on four targets 1.
Cell wall
2.
Cytoplasmic membrane
3.
Ribosomes
RNA molecules involved in transcription of genetic information.
4.
CLASSIFICATION: Antibiotics are broadly classified in to •
Bactericidal antibiotics- they kill bacteria
•
Bacteriostatic antibiotics- they inhibit bacterial proliferation.
Based on their mechanism of action antibiotics are classified as I)
Inhibit cell wall synthesis: penicillins, cephalosporins, vancomycin, bacitracin, cycloserine.
II)
Damage of cell membrane causing leakage of cell contents: polymixins, amphoterecin B, nystatin.
III)
Bind to ribosomes and inhibit protein synthesis: chloramphenicol, tetracyclines, erythromycin, clindamycin, aminoglycosides.
IV)
Inhibit DNA gyrase: fluoroquinolones.
V)
Inhibit DNA function: rifampicin.
VI)
Inhibit DNA synthesis: acyclovir, zidovudine.
VII)
Interefere with metabolism: sulfonamides, trimethoprim.
ANTIBIOTICS Fluoroquinolones
ANTIBACTERIAL SPECTRUM
DOSE
ROUTE OF ADMINISTRATION
Gram negative and gram positive and anaerobic organisms.
1)
Norfloxacin
400mg BD
Oral
2)
Ciprofloxacin
250750mg
Oral
BD 3)
4)
Pefloxacin
Ofloxacin
400mg BD 400mg 12hrly
Oral
200400mg OD
Oral
200400mg 12-24 hrly
IV
IV
5)
Lomyfloxacin
400mg OD
Oral
6)
Sparfloxacin
200400mg OD
Oral
DOSE
ROUTE OF ADMINISTRATION
ANTIBIOTICS
ANTI BACTERIAL SPECTRUM
Penicillins
Narrow antibiotic spectrum effective against gram positive organisms
1)
Sodium penicillin G
0.5-5MU 4-6hrs
IV/IM
2)
Procaine G
0.5-1MU 12-24 hrs
IM
penicillin
3)
Benzathine penicillin G
1.2-2.4 DEEP IM MU 3-4 WKS
SEMISYNTHETIC PENICILLINS 1)
Dicloxacillin
200500mg QID
2)
Naficillin
1-2 gms IV 4-6hrs
3)
Ampicillin
250mg or Oral 1 gm qid
4)
Ampicillin salbactum
5)
Amoxicillin
250500mg tid
6)
Amoxicillin and clauvlanic acid
250mg Oral and 125 mg tid
7)
Piperacillin
3-4 gms IV 4-6hrly
8)
Ticarcillin
3gms 6hrly
and
1gm and IV 0.5gm 68hrly
CEPHALOSPORINS First generation
Oral
Have wider activity than penicillin. Gram positive resistent to
Oral
4- IV
penicillin 1)
Cephalothin
1-2gms 6hrly
IV
2)
Cephalozin
0.5-1gm 6hrly
IM/IV
3)
Cephalexin
0.25-1gm qid
Oral
4)
Cefadroxil
0.5-1gm bid
Oral
IM/IV
Second generation
Gram negative resistent to beta lactamases
1)
Cefuroxime
0.751.5gm 8hrly
2)
Cefumandole
0.5 -2gms IM/IV 4-8 hrly
3)
Cefuroxime
0.250.5gm bd
Oral
4)
Cefaclor
0.250.5gm
Oral
1-2gms
IM/IV
Third generation
1)
Cefotaxime
Highly resistent to beta lactamases. Effective against gram negative organisms
8hrly 2)
Ceftriaxone
1-2gms od
3)
Cefperazone
1-2gms 8- IM/IV 12hrly
Fourth generation
1)
Serious gram negative infections
Cefipime
Broad antibiotics
IM/IV
1-2gms 12hrly
IV
spectrum
TETRACYCLINES
Gram positive, gram negative, rikketsciae, chlamydiae, mycoplasma
1)
Chlortetracycline
250500mgs qid
Oral
2)
Tetracycline
250500mgs qid
Oral
3)
Doxycycline
200mgs initially then 100mgs od
Oral
4)
Minocycline
200mgs initially then
Oral
100mgs od Chloramphenicol
Gram negative, gram positive, anaerobic bacteria, chlamydiae, mycoplasma
AMINOGLYCOSIDES
Gram negative anaerobic bacilli
1)
Streptomycin
1IM 2gms/day
2)
Gentamycin
3-5mg/kg IM/IV in three divided doses
3)
Tobramycin
3-5mg/kg IM/IV in three divided doses
4)
Amikacin
15mg/kg IM/IV in 2-3 divided doses
5)
Netilmycin
4-6mg/kg IM/IV in 2-3 divided doses
MACROLIDES Erythromycin
Narrow spectrum,
gram positive and few gram negative organisms 1)
Erythromycin stearate
250Oral 500mgs qid 7-14 days
2)
Erythromycin estolate
250Oral 500mgs qid 7-14 days
3)
Roxitromycin
150mgs
4)
Azitromycin
500mgs then 250mgs od next three days
Oral
Adverse effects 1.
Fluoroquinolones:-Tendinitis with assosciated risk of tendon rupture.they damage growing cartilage resulting in anthrppathy . Hence contraindicated up to 18 years of age.
2.
Pencillin:-(i) Hypersensitivity reactions ranging from skin rashes,urticaria,fever,bronchospsm,serum rickness and rarely exfoliature dermatitis and anaphylaxis.
(ii) Jarish-herxheimex reaction -when pencillin is injected in a patient with syphilis,there is sudden destruction of spirochetes and release of its tylio products which triggers a reaction with fever,myalgia,shivering. 3.
Cephalosporins :-- 20% patients allergic to pencillon show reactivity to cephalosporins
4.
Tetracyclines:-hepatoloxity,renal toxity,phototoxity. out dated tetracyclines cause fanconils syndrome.(vomting,polyuria,protienuria,glycosuria) effect on teeth and bones:--tetracyclines chelate calicium.the calicium tetracycline orthophosphate complexes yet deposited in developing teeth and bones .he deormites depend on time of tetracycline administration.
Period deformity
structures affected
mild pregnancy to 5 months of dicicluous teeth broconish discolouration,ill portnatal formed,more caries suseptible 2months to 5 years of age pigmentation,discolouration
perment teeth
pregnancy and childhood up to 8 depressed bone growth
skeleton
Chloramphenicol:--
Gray baby syndrome:-- new born babies may develop vomting, hypotension, hyperthermia and ashen gray cyanosis asthey cannot metabolise and excret chloramphenicol. Inoglyclorids:-- Ootoloxity,nephrotoxity Erthromycin:-Inhibits hepatic metabolism and rises plasma levels of carbemazepine, terfanidine, valproate,aligoxin and results in their toxicity. Roxythromicin , clarithromicin and Azithomyccin do not have any drug interactions. Principles for choosing Antibiotics:--In most clinical situations,it is easy to determine whether a patient has an infection. Locally, the classical signs and symptoms of pain,swelling,surface erythema,pus formation and sustematically,fever,lymphadenopathy,malaise, a toxic appearance and an elevated white blood cell count are formed. Infections are ultimately cured by the host and not by antibiotics . Antibiotic therapy reduces bacterial challenges and allows hort defences to complete the treatment. Initial empirical therapy may be instituted with a fair degree of reliability if the following criteria are met . (i)
Site and features of infection have been well met
(ii)
Circumstances leading to infection are well known.
(iii)
Organism or organisms that most commonly cause such infections are well known. Definitive therapy is done after culture reports are received . Early infections that present as cellulitis with out abcess formation are most caused by aerobic bacteria. As the infection becomes more severe ,the microbiology becomes more severe ,the
microbiology becomes a mixed flora of aerobic and anaerobic bacteria are no longer able to survive in hypoxic acidic environment. Principles:--1.
State of host defences:-Antibiotics help in situations which the host has been over whelmed by bacteria or when especially virulent bacteria are involved .When a patients defences are impaired ,antibiotics, play a more important role in control of infections. Eg:-- cancer,leukemias,malnutrition,poosly controlled diabetes. Cycotoxic drugs and immune supressents like glucocorticoids, azathioprine, cyclosprin affect host defences. Aggressive antibiotic therapy must be considered in treating established infections in patients in any of these categories . Surgicaldrainage and incision may also deviate the use of an antibiotic or may increase the effectiveness of an antibiotic as vascular flow is restored. Determination of Antibiotic sensitivity:-Staphy lococcus infection must be treated with antibiotic susceptibility information in hand.Pencillin G can be used only if sensitivity studies support its effectiveness.Pencillinnase resistant pencillins should be used. There is an increasing incidenceof resistance to pencillinase resistant drugs ,which currently is high enough to warrant antibiotic routine susceptibility testing for staphylococcal infection. Pencillinďƒ Excellent for treatment of streptococcus infection. ďƒ Good to excellent for major odontogenic infectons Erythromycinďƒ effective against streptococcus ,pepto streptococcus, preuotella/
Clindamycingood for streptococcus. CephalexinModerate active against streptococcus,good age MetronidazoleNo action against Streptococcus.Excellent activity against anaerobes
Use of narrow spectrum Antibiotic :-Antibiotic with narrowest anti bacterial spectrum should be used. Eg:--If streptococcus is sensitive to pencillin, cephalosporin and tetracycline . Pencillin should be used because it has narrowest spectrum. The other two act against a variety of gram negative organisms and their use leads to development of resistent organisms. Use of narrow spectrum antibiotics minimize the risk of super infections because they allow large proportions of host flora to be maintained. USE OF LEAST TOXIC ANTIBIOTICS: Select least toxic drugs from among those that are effective. Eg: bacteria causing odontogenic infections are sensitive to penicillin and chloramphenicol. Though chloramphenicol is more effective than penicilin, it is not preferred because of its potential to cause severe bone marrow depression. PATIENT DRUG HISTORY: Two aspects should be reviewed in drug history •
Previous allergic reactions
•
Previous toxic reactions
Allergy rate to penicillin is approximately 5% so history of previous allergy should be abtained. It is well documented that co-incident allergies to cephalosporins and penicilins do exist. So if patient is allergic to penicillin, cephalosporins should be used unless it is deemed necessary only after preparations are made to treat severe reactions. Penicillin allergy: skin testing should be done 24hrs before penicillin administration. Potential reactions with other drugs, the patient is taking is considered.
USE OF BACTERICIDAL RATHER THAN BACTERIOSTATIC DRUGS: Advantages of bactericidal antibiotics: •
Less reliance on host resistance
•
Killing of bacteria by antibiotic itself
•
Faster results than bacteriostatic drugs
•
Greater flexibility with dosage intervals
Bactericidal drugs exert their influence after they are incorporated into the bacterial cells and the cell eventually dies. Bacteriostatic drugs exert their action only when present in patients tissues so the bacteria resume their growth after drug is eliminated. So rigorous time schedule should be followed up. In immunocompromised patients bactericidal drugs are preferred to bacteriostatic drugs. Cotrimoxazole, fluoroquinolones, penicillins, cephalosporins, aminoglycosides, vancomycin, teicoplanin are bactericidal. Sulfonamides, tetracyclines, chloramphenicol are bacteriostatic. Erythromycin is bacteriostatic in low doses and bactericidal in higher doses. USE OF ANTIBIOTICS 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. Standard drug should not be disapproved for an unapproved drug without good reason. The newer drug should be effective for bacteria against which no other antibiotic is effective. Eg. Methicillin for penicillinase. Such drugs should be used only for those bacteria with proven sensitivity. We can select a new antibiotic if it is less expensive, more potent, less toxic, few side effects than older one but should be used with caution. COST OF ANTIBIOTIC: Reasonably affordable price should be considered. PRINCIPLES OF ANTIBIOTIC ADMINISTRATION: Antibiotic must be administered properly. This involves consideration of dosage, route of administration and combination therapy. PROPER DOSE: Any drug should be administered in sufficient amounts to achieve deserved therapeutic effect but should not cause injury to host. Minimum inhibitory concentration of an antibiotic for a specific bacteria should be calculated. For therapeutic purposes, the peak concentration of antibiotics at the site of injection should be 3-4 times the minimum inhibitory concentration. Dose above this level does not improve the therapeutic results but will cause toxicity. Eg. Gentamicin is effective in concentrations up to 4-6 microgram/ml but the incidence of nephrotoxicity increases dramatically at 10 microgram/dl plasma level. In cases of infections isolated from blood supply, increased antibiotic doses can be given. The high plasma concentration can cause greater amount of antibiotic to reach the sealed of bacteria by simple diffusion.
Sub therapeutic doses should not be given as they supress clinical manifestation without actually killing microbes and hence may result in recurrence of infection after discontinuation of drug. PROPER TIME INTERVAL: The usual dosage interval for the therapeutic use of antibiotic is four times the t1/2. At five times t1/2 95% of drug is excreted. Eg. T1/2 of cefazolin is 2hrs . so interval between doses should be 8hrs. In patients with compromised renal function, prolonged interval should be given because excessive plasma levels due to decreased clearance would cause toxicity.
ROUTE OF ADMINISTRATION: Some times only parenteral route of administration would provide adequate serum level of antibiotic. If given orally, should be given 30mins before or 2 hrs after meals for maximum absorption. When long term parenteral administration is necessary IV is preferred over IM as IM is poorly accepted by patient. CONSISTENCY IN ROUTE OF ADMINISTRATION: In case of serious infections parenteral route is preferred. After initial response we usually switch to oral administration. But this may cause recurrence of infection as blood levels of drug are lower when we switch to oral route on second or third day of therapy. After 5 days oral levels are sufficient. “Maintenance of peak blood levels of antibiotics for adequate period is important to achieve maximum tissue penetration and effective bacterial killing.� In case of mild infection oral administration is sufficient. COMBINATION ANTIBIOTIC THERAPY: Combination antibiotic therapy should be avoided for routine infections as it may provide broad spectrum exposure leading to emergence of resistent bacteria.
Indications of combination therapy: •
When it is necessary to increase the antibacterial spectrum in patients with life threatening sepsis of unknown cause.
•
When increased bactericidal effect against a specific organism is desired.
•
To prevent rapid emergence of resisrent bacteria. Eg: treatment of tuberculosis by multiple drugs.
•
In emperic treatment of certain odontogenic infections. Eg: severe cellulitis type of infections rapidly progressing posteriorly around the lateral and retropharyngeal spaces, bactericidal activity against streptococcus and oral anaerobes is important. As prevotella is resistent to penicillin, both parenteral penicillin and metronidazole should be given to provide bactericidal activity against both streptococcus and anaerobes.
•
Patient monitoring : patient should be monitered for response to treatment and development of alveolar reactions. Response to treatment: no response to antibiotics occurs in 24-48 hrs. Action begins after second after second day. Objective signs and symptoms are decreased temperature, swelling pain. Eradication of infection is reached by third day with decrease of symptoms. In case of uncomplicated odontogenic infections improvement begins on second day of therapy and marked resolution is seen by third day and an additional two days is needed to resolve the infection. In case of severe infection, seven day course is needed. If patients condition does not improve after initial therapy, antibiotic should not be changed immediately as it takes some time and following clarifications should be done. 1.
Carefully evaluate the patient
2.
Look for need for additional surgery to drain pus or release pressure or remove foreign body.
3.
Other possible sites of infection should be evaluated
4.
Portals of entry such as IV catheter should be checked
5.
Adequate hydration and nutritional support are necessary.
If initial therapy failed the following clarifications should be made 1.
Is the route of administration adequate to deliver effective dose of drug
2.
Is patient taking antibiotic prescribed
3.
Are physcians order followed
4.
Is choice of antibiotic correct
If initial therapy failed culture should be done before changing the drug. A second empirical choice should be avoided due to low success rate. Development of adverse reactions: Adverse reactions may be in the form of anaphylactic reaction or less severe reaction associated with edema urticaria and itching or there may be delayed reaction presenting only as a low grade temperature. Patient should be cautioned about allergy. If allergic reaction occurs it should be treated and patient should be informed about the drug used and type of reaction and should be advised caution in future. ANTIBIOTIC ASSOCIATED COLLITIS: It is a toxic reaction. It was originally associated with clindamycin but noe ampicillin, amoxicillin and cephalosporins are also found responsible. Clinical features: watery diarrhoea, creamping abdominal pain, fever. Treatment: Discontinue causative antibiotic. Restore fluid and electrolyte balance. Administer clostridial antibiotics., vancomycin and metronidazole can be used.
SUPER INFECTION AND RECURRENT INFECTION: In normal state, normal flora acts as a defence mechanism, but when this mechanism is altered or eliminated due to use of antibiotics superinfection occurs. Eg: candida infection due to long term treatment with penicillins as in actinomycosis and osteomyelitis. In case of osteomyelitis and actinomycosis more carefull and longer follow up is necessary as the nonvital bone provides a barrier to antibiotic effectiveness and is a potential focus of re-infection. In such cases, re institution of antibiotics should be done with additional surgical intervention if necessary. THERAPEUTIC USES OF ANTIBIOTICS IN ORAL AND MAXILLOFACIAL SURGERY: ABSCESS: Penicillin is the drug of choice. Adjunctive treatment like endodontic treatment, extraction of tooth or surgical drainage should be done. PERICORONITIS: Anaerobic bacteria including gram positive cocci and gram negative rods are obtained on culture. Penicillin is the drug of choice. ODONTOGENIC INFECTIONS AND DEEP FASCIAL SPACE INFECTIONS OF DENTAL ORIGIN: Well localized and easily drained dentoalveolar abscess can be treated by surgical drainage. Antibiotic therapy is needed in case of •
Poorly localized, extensive abscess associated with diffuse cellulitis.
•
Abscess in case of immunocompromised patients, patients with poorly controlled diabetes and patients on renal dialysis.
Majority of infections consists of mixed aerobic and anaerobic flora. According to MOENING(1989) “it would seem presumptuous to state that penicillin is currently not effective against most odontogenic infections and premature to consider substituting another antibiotic as the drug of chioce for mild to moderate odontogenic infection especially when low cost and lack of toxicity is considered.” In case of more severe infections antibiotic sensitivity tests may be needed. Metronidazole is effective supplement to penicillin as it acts against anaerobes. Erythromycin is poorly absorbed and is less effective in case of
odontogenic infections. Azithromycin is better tolerated than erythromycin. In case of very severe infections combination of amoxicillin and clavulanic acid is preferred. First and second generation cephalosporins are used. Tetracyclines are not recommended. Minocycline and doxycycline can be used for low grade odontogenic infections. Patients requiring hospitalization for odontogenic infections and for immunocompromised host, the treatment regimen is CLINDAMYCIN alone (or) CLINDAMYCIN+METRONIDAZOLE (or) GENTAMICIN (or) PARENTERAL AMPICILLIN+SULBACTUM OSTEOMYELITIS: causative organisms are staphylococcus epidermis, hemolytic streptococci, prevotella, porphyromonas. Most of these organisms are penicillin resistent so metronidazole is effective. ANTIBIOTIC REGIMEN FOR OSTEOMYELITIS OF JAWS: Regimine 1: for hospitalized /medically compromised patient or when IV therapy is indicated. 1)
Aq penicillin 2 million units IV 4 hrly , metronidazole 500mg 6 hrly
When improved for 48-72hrs, switch to penicillin V 500mg per oral 4 hrly plus metronidazole 500mg per oral 6 hrly for an additional 4-6 weeks. Ampicillin/sulbactum 1.5 -3 gms IV 6hrly, when improved for 48-72 hrs switch to amoxicillin/clavunate 875/125 mg per oral bid for an addditional 4-6 weeks. Regimen 2: for out patient treatment PenicillinV 2gm plus metronidazole 0.5 gm 8hrly per oral for 2-4 weeks after last sequestrum removed and patient without symptoms. Clindamycin 600-900mg 6hrly IV then clindamycin 300-450mg 6hrly per oral.
Cefoxitin 1.0 gm 8hrly IV or 2gm 4hrly IM or IV untill no symptoms, then switch to cephalexin 500mg 6hrly per oral for 2-4 days. For penicillin allergic patients, clindamycin and cefoxitin can be given. Cephalosporins are not first choice in the management of osteomyelitis because they are only moderately effective against oral anaerobes and their broad spectrum coverage increase antibiotic complications. Erythromycin and other macrolides like clarithromycin, azithromycin, are not recommended for treatment of osteomyelitis because they are no longer reliably effective against the oral streptococci and anaerobes. CHRONIC SUPPURATIVE OSTEOMYELITIS: Usually requires surgical procedures such as sequestrectomy and removal of foreign bodies such as wires, bone plates etc. Treatment should begin with IV therapy and continue even after discharge using home IV therapy usually with ampicillin/salbactum sodium because it is stable for 24hrs after mixing with IV fluids. IV therapy for 2 weeks or untill the patient has shown improvement for 48-72 hrs. Oral therapy should be continued for 4-6 weeks after patient has no symptoms or from the date of last debridement. If ampicillin/sulbactum sodium is ineffective clindamycin therapy is indicated. Antibiotic impregnated beads deliver higher concentration of antibiotic into wound bed and in immediate proximity to infected bone as antibiotic is leached out from beads, thus low systemic toxicity. These are useful for chronically infected bone associated with fracture and in chronic sclerosing osteomyelitis refractory to systemic antibiotics. eg.tobramycin or gentamicin in acrylic resin bone cement beads. They are removed after 10-14 days. SALIVARY GLAND INFECTIONS: Empirical therapy: Out patient- amoxicillin+clavulanic acid In patient- ampicillin+sulbactum(parenteral)
In case of penicillin allergy clindamycin is used. Erythromycin is not indicated due to high bacterial resistance. Azithromycin and clarithromycin can be used in out patient community acquired acute bacterial parotitis. Antibiotic therapy should be continued untill atleast 1 week after resolution of signs and symptoms. ANTIBIOTIC PROPHYLAXIS IN HEAD AND NECK SURGERY: Antibiotic prophylaxis in oral and maxillofacial surgery aims the prevention of infection of the surgical wound, either due to characteristics of surgery or the general state of the patient. Prophylactic antibiotic therapy creates an area of resistance to microorganisms by means of antibiotic serum concentrations that may avoid the multiplication and spread of bacteria through the surgical injury. ADVANTAGES: •
Decreased patient infection
•
Decreased post operative morbidity
•
Decreased cost of health care
•
Decreased amount of antibiotics used.
DISADVANTAGES: •
They may alter host flora
•
Sometimes when the risk of infection is low, antibiotics donot have effect.
PRINCIPLES: 1.RISK OF INFECTION MUST BE SIGNIFICANT: a) Bacterial innoculum should be sufficient size to cause infection. b) Prolonged and extensive surgery. c)Presence of foriegn body d) Depressed host defences
2.CHOOSE CORRECT ANTIBIOTIC: a) Antibiotic must be effective against causative organism. b) Choose narrow spectrum antibiotic c) It should be least toxic d) Select bactericidal antibiotic 3.ANTIBIOTIC PLASMA LEVELS MUST BE HIGH: a) Prophylactic doses should be higher than therapeutic doses b) Antibiotic should diffuse into all fluids and tissue spaces where surgery is going on. c) Doses should be atleast two times the therapeutic dose. Eg:penicillin-1gm Cephalosporins-1gm Clindamycin-300mg Clarithromycin-500mg 4.ANTIBIOTIC MUST BE TIMED CORRECTLY: For maximum benefit ,antibiotic should be given before surgery begins. If the surgery is prolonged and intra operative dose is required,intervels should be shorter(half the usual therapeutic dose interval).This will ensure that the peak plasma levels are maintained and avoids periods of inadequate antibiotic levels in tissue fluids. Eg: penicillin should be given every 2 hrs. Cephalexin should be given every 2 hrs Clindamycin should be given every 3 hrs 5.USE SHORTEST ANTIBIOTIC EXPOSURE THAT IS EFECTIVE:
No additional antibiotic is neede after surgery. Final dose of antibiotic should be given at the termination of surgery. ANTIBIOTIC PROPHYLAXIS OF WOUND INFECTION: 1.PARENTERAL REGIMEN: 1. Penicillin: •
Preoperative 1 million units IV
•
Intraoperative 1 million units IV q2hrs
•
Post operative 1 million units IV in recovery room
2.Cephazolin(penicillin allergic patients) •
Preoperatively 1gm IV
•
Intraoperatively 1gm Ivq 4h
•
Postoperatively 1gm IV in recovery room.
3.Clindamycin •
Preoperatively 600mg IV
•
Intraoperatively 600mg IV 4h
•
Post operatively 600mg IV in recovery room
2.ORAL REGIMEN: 1.Penicillin •
Preoperative 2mg po 30min before
•
Intraoperative 1mg per oral 2hrly
•
Post operative 1mg per oral 2hrly
2. erythromycin
•
Preoperative 1gm 1hr before
•
Intraoperative 500mg per oral 2hrs
•
Post operative 500mg peroral 2hrs
PROPHYLAXIS FOR SUBACUTE BACTERIAL ENDOCARDITIS: Parenteral-oral combined regimen: 1.
2.
Preoperatively 30-60 mins •
Aqueous penicilinG – 1million units IM
•
Procaine penicillinG – 6,00,000 units IM
Post operatively 8 doses PenicillinV 500mg peroral 6hrly.
•
Children: Preoperatively 30-60mins •
Aqueous penicillinG- 30,000 units/kg IM
•
Procaine penicillinG- 6,00,000 units IM.
Post operatively 8doses a)
PenicillinV I)
Less than 27kg(60lb) 250mg peroral 6hrly
II)
More than 27kg(60lb)500mg peroral 6hrly
Oral regimen: ADULTS: 1.
Preoperatively 30-60 mins penicilinV – •
Procaine penicillinG – 6,00,000 units IM
3.
Post operatively 8 doses PenicillinV 500mg peroral 6hrly.
•
Children: Preoperatively 30-60mins •
Aqueous penicillinG- 30,000 units/kg IM
•
Procaine penicillinG- 6,00,000 units IM.
Post operatively 8doses b)
PenicillinV III)
Less than 27kg(60lb) 250mg peroral 6hrly
IV)
More than 27kg(60lb)500mg peroral 6hrly
FOR PATIENTS ALLERGIC TO PENICILLIN: Adults: Preoperatively ½-2hrs Erythromycin 1.0gm peroral Postoperatively 8doses Erythromycin 500mg peroral 6hrly Children: Preoperatively ½-2hrs Erythromycin 20mg/kg peroral Postoperatively 8 doses Erythromycin 10mg/kg peroral 6hrly ANTIBIOTIC MISUSE:
The misuse and increased use of antibiotics are inducing the rapid growth of antibiotic resistant bacteria(super bug), making it difficult for clinicians to treat infections. PREVENTION: a)
Narrow spectrum antibiotics should be prescribed.
b)
Microbiology lab results should be the only factor determining the type of antibiotic medication prescribed to patients.
c)
Patients should be educated regarding misuse and increased use of antibiotics.
d)
Patients should follow prescribed directions.
e)
Sale of over the counter antibiotics should be emphasized upon.
ANTIBIOTIC RESISTANCE: The increase in antibiotic resistant bacteria is largely due to wide spread use of antibiotics in medicine, animal care and agriculture. MULTIPLE DRUG RESISTANT ORGANISMS: Multiple drug resistant organisms are resistant to treatment with several, often unrelated, antimicrobial agents. Some of the most important types of multiple drug resistant organisms are •
MRSA- methicillin/oxacillin resistant staphylococcus aureus
•
VRE- Vancomycin resistant enterococci
•
ESBLs-extended spectrum beta lactamases(which are resistant to cephalosporins and monobactams)
•
PRSP-Penicillin resistant streptococcus pneumoniae
MECHANISM OF ANTIBIOTIC RESISTANCE IN BACTERIA: 1)
Chloramphenicol- reduced uptake into cell
2)
Tetracycline- active efflux from cell
3)
Beta lactums,erythromycin, lincomycin- eliminates or reduces binding of antibiotic to cell target.
4)
Beta lactums, aminoglycosides,chloramphenicol- enzymatic cleavage or modification to inactive antibiotic molecule
5)
Sulfonamides, trimethoprim- metabolic bypass of inhibited reaction
PREVENTION: •
Search for new antibiotics
•
Stop the use of antibiotics as growth promoting substances in farm animals
•
Use the right antibiotic
•
Stop unnecessary antibiotic prescription
•
Finish antibiotic prescription
CONCLUSION: The discovery of antibiotic was a leap in modern medicine. They have been able to stop the growth or kill many different kinds of microorganisms. However, bacteria have proven to be much more innovative and adaptive than we imagined and have developed resistance to antibiotics at an ever increasing pace. Bad practices and mismanagement have only exacerbated the situation. However, with more research education of public and well thought out regulations, the problems can be solved.