ASSIGNMENT

Prophylactic Use of Antibiotics

SUBMITTED TO:

Prof. Dr. Bashir Ahmad

SUBMITTED BY:

Ijaz Ali Roll no: 643 Ammar Sarwar Roll no: 636 Kamal Sikandar Roll no: 642
1

Prophylactic Use of Antibiotics

Definition: A prophylaxis is a measure taken to maintain health and prevent the spread of disease. Antibiotic prophylaxis is the focus of this article and refers to the use of antibiotics to prevent infections.

Purpose : Antibiotics are well known for their ability to treat infections. But some antibiotics also are prescribed to prevent infections. This usually is done only in certain situations or for people with particular medical problems. For example, people with abnormal heart valves have a high risk of developing heart valve infections even after only minor surgery. This happens because bacteria from other parts of the body get into the bloodstream during surgery and travel to the heart valves. To prevent these infections, people with heart valve problems often take antibiotics before having any kind of surgery, including dental surgery. Antibiotics also may be prescribed to prevent infections in people with weakened immune systems such as those with AIDS or people who are having chemotherapy treatments for cancer. But even healthy people with strong immune systems may occasionally be given preventive antibioticsif they are having certain kinds of surgery that carry a high risk of infection, or if they are traveling to parts of the world where they are likely to get an infection that causes diarrhea, for example. In all of these situations, a physician should be the one to decide whether antibiotics are necessary. Unless a physician says to do so, it is not a good idea to take antibiotics to prevent ordinary infections. Because the overuse of antibiotics can lead to resistance, drugs taken to prevent infection should be used only for a short time.
2

Some Important Examples

1. African Trypanosomiasis:(sleeping sickness) African trypanosomiasis is caused by Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense transmitted be tsetse flies (Glossina species). Disease is characterized by two stages.Hemolytic stage(Irregular fever,anemia,joint pain) and meningoencephalitic stage(Insomnia,sensory and motor disorders) Pentamidine is used in chemoprophylaxis only against Gambian type and in rhodesiense species Pentamidine may suppress early symptoms.Excretion of Pantamidine is slow therefore one intramuscular injection (4mg/kg , maximum 300mg) protects for 3-6 months. The drug is toxic and should only be used for persons at high risk of exposure. 2. Anthrax: Anthrax is caused by gram positive rod Bacillus anthracis transmitted via infected animals or animal hides (sheep , cattle, horse, goats and swine). Three types of anthrax. Cutaneous anthrax(exposed Skin vesiculates->ulcerates>necrosis->purple black eschar).Inhalational anthrax (Dyspnea,nasal congestion,fever,meningitis).Gastrintestinal anthrax (Abdominal pain,diarrhea or constipation) First line agents in chemoprophylaxis includes 1. Ciprofloxacin 500mg b.d or 400mg every 12 hours intravenously) 2. Doxycycline 100mg every 12 hours orally or intravenously) Second line agents include: 1. Amoxicillin 500mg three times daily orally.
3

2.

Penicillin G 2mU every 4 hours intravenously.

3. Animal And Human Bite wounds: Prophlaxis is indicated in high risk bites e.g Cat bites in any location Dicloxacillin, 0.5 g orally four times a day for 3-5 days. Hand bites by animals or humans (Penicillin V, 0.5g orally four times a day for 3-5 days. Immunocompromised and individuals without functional splees are at high risk of developing bacteremia and sepsis following bites. 4. Burns: Systemic infections (Methicillin resistant staphylococcus aureus, Pseudomonas, Klebsiella, Methicillin resistant S. Epidermidis) remains a leading cause of morbidity among patients with major burn injuries. Trimethoprim-Sulfamethoxazole is used prophylactically in burn patients to prevent MRSA infection in ventilator dependent burn patients. 5. Infective Endocarditis: Diseasecaused by Staphylococcus, Streptococcus, Hemophilus, Actinobacillus,Cardiobacterium,Eikenella , Kingella and Enterococcus species . Characterized by cough , dyspnea, abdominal pain, heart murmur , peripheral lesion petechiae(on the palate or conjunctiva or beneath the fingernails) subungual hemorrhages or painless erythmatous lesions of palm or soles. Prophylaxis is indicated in 1. Dental, Respiratory or Esophageal Procedures: Orally: Amoxicillin 2g one hour before procedure Cephalexin or cefadroxil 2g one hour before procedure. Azithromycin or Clarithromycin 500mg one hour before procedure. Penicillin Allergy (Clindamycin 600mg one hour before procedure).
4

Parenteral: Ampicillin 2g IM or IV 30 minutes before procedure. Cefazoline 1g IM or iV 30 minutes before procedure. Penicillin Allergy( Clindamycin 600mg 1 hour before procedure). 2. Gastrointestinal(except esophageal) or Genitourinary Procudures: High Risk Patients: Ampicillin 2g IM or IV plus Gentamycin 1.5mg/kg(not to exceed 120mg) 30 minutes before procedure. 6 hours later ampicillin 1g IM or IV or amoxicillin 1g orally. Penicillin Allergy{ Vancomycin, 1g IV over 1-2 hours, plus Gentamycin 1.5mg/kg(not to exceed 120mg) IV or IM complete infusion or injection 30 minutes before procedure.} Moderate Risk Patients: Amoxicillin 2g orally 1 hour before procedure or ampicillin, 2g IM or IV 30 minutes before starting procedure. Penicillin Allergy { Vancomycin 1g IV over 1-2 hours complete infusion 30 minutes before procedures.}

6. Esophageal Varices: Dilated submucosal veins results in upper gastrointestinal bleeding. Cirrhotic patients with upper GI bleeding have a greater than 50% chance of developing severe bacterial infection. Prophylactic therapy by Norfloxacin 400mg or other quinolone either oral or intra nasal tube twice daily for atleast 7 days is recommended. 7. Group B Streptococcal infection in Pregnancy: The routine recommended regimen for prophylaxis is Penicillin G, 5 million units intravenously as loading dose the 2.5 million units intravenously every 4 hours until delivery. In penicillin allergic patients one should give Cefazolin, 2g intravenously as initial dose then 1g intravenously every 8 hours until delivery.In
5

patient with high risk of anaphylaxis use Vancomycin 1g intravenously every 12 hours until delivery or after confirmed susceptibility of group B streptococcal isolates Clindamycin 900mg intravenously every 8 hours or erythromycin 500mg intravenously every 6 hours.

8. Immunocompromised Host: Trimethoprim-sulfamethoxazole one double strength tablet three times a week, one double strength tablet twice daily on weekends or one single strength tablet daily for 3-6 months is frequently used to prevent Pneumocystis infections in transplant patients.It may also decrease the incidence of bacterial pneumonia, urinary tract infections, nocardia infections and toxoplasmosis. In patients allergic to trimethoprim-sulfamethoxazole, aerosolized Pentamidine is used in a dosage of 300mg once a month as is dapsone, 50mg daily or 100mg three times weekly.(G6PD levels should be determined before therapy with latter is instituted) Acyclovir or Ganciclovir is used in prophylaxis of CMV infection at a dose of 200mg orally three times daily for 4 weeks(bone marrow transplant) to 12 weeks(other solid organ transplant).

Prophylaxis with antifungal agents to prevent invasive molds (primarily aspergillus) and yeast (primarily candida). Moderate dose (0.5mg/kg/day) and low dose(0.1-0.25mg/kg/day) Amphotericin B, Liposomal aerosolized preparations of Amphotericin B and Itraconazole are used in neutropenic patients.

9. Influenza: Chemoprophylaxis is accomplished with either Amantadine or Rimantadine or newer neuraminidase inhibitors Zanamivir and oseltamivir. Amantadine (200mg/d orally in two divided doses or 100mg/d in elderly who are susceptible to CNS side effects) are effective only against influenza A. Oseltamivir(75mg/d) and Zanamivir(10mg inhaled daily) are effective against influenza A and B. 10. MAC(mycobacterium avium complex) infections:
6

Infection characterized by coin lesion,Bronchitis. Prophlaxis prevent disseminated disease and prolong survival, it include single drug regimens of Clarithromycin 500mg twice daily, Azithromycin 1200mg once weekly or Rifabutin 300mg once daily.

11. Malaria: None of the drugs prevent infection. However Proguanil, Chloroguanil, Atovaquone and Primaquine and other antibiotics prevent maturation of early P falciparum. Blood schizonticides destroy circulating plasmodia and thus prevent malarial attacks. When given weekly for 4 weeks after departure from the endemic era, result in cure of P.falciparum and P malariae infections. Only primaquine destroys the hypnozoites of P.vivax and P.ovale and when given with blood shizonticide prevent relapse from infection. 12. Meningococcal Meningitis: Rifampin is the drug of choice in a dosage of 600mg twice a day for 2 days.A single 500mg oral dose of Ciprofloxacin or one intramuscular 250mg dose of ceftriaxone in adults is also effective. 13. Peritonitis: Upto 70% of patients who survive an episode of spontaneous bacterial peritonitis will have another episode within 1 year. Prophylactic therapy with Norfloxacin 400mg/d, Ciprofloxacin 750mg weekly or trimethoprimsulfamethoxazole one double strength tablet daily has been shown to reduce the rate of recurrent infections to less than 20% and is recommended. Prophlaxis should be considered also in patients who have not had prior bacterial peritonitis but are at increased risk of infection due to low protein ascites(total ascites protein <1g/dl) 14. Plague: Drug prophylaxis may provide temporary protection for persons exposed to the risk of plague infection particularly by the respiratory route. Tetracycline hydrochloride 500mg orally once or twice daily for 5days is effective. 15. Pneumoccystis jiroveci (Pneumocystis carinii) infection:
7

Primary prophylaxis for opportunistic infections like pneumocystis pneumonia should be offered to patients with CD4 counts below 200 cells/micro lite, a CD4 lymphocyte percentage below 14% or weight loss or oral candidiasis.Patients with a history of pneumocystis pneumonia should receive secondary prophylaxis until they have had a durable virologic response to HAART for at least 3-6 months and maintain a CD4 count of >250cells/ micro liter. Trimethoprim-sulfamethoxazole one double strength tablet 3 times a week to one tablet daily prevent pneumocystis pneumonia. Dapsone 50-100mg daily or 100mg twice or three times a week is a second line prophylactic agent with minimal side effects. Before prescribing dapsone clinicians should make certain that the patient is not G6PD deficient. If above two regimens are not working then Atovaquine 1500mg daily as oral suspension. Finally aerosolized Pentamidine 300mg monthly can be used if no systemic agent can be tolerated. 16. Rape or sexual assault: Ceftriaxone 125mg intramuscularly to prevent gonorrhea. In addition give Metronidazole 2g as a single dose and Doxycycline 100mg twice daily for seven days to treat chlamydial infection. Incubating syphilis will probably be prevented by these medications but the VDRL test should be repeated 6 weeks after assault. 17. Rheumatic fever: Patients who have had rheumatic fever should be treated with a continuous course of antimicrobial prophylaxis for at least 5 years. Effective regimens are Erythromycin 250mg orally twice daily or Penicillin G 500mg orally daily. 18. Surgical wound infection: The development of a post operative wound infection is a common and extremely important cause of morbidity and prolonged hospital stays. Cefazolin 1-2 g intravenously for procedures like superfacial cutaneous, head and neck, neurologic, thoracic, noncardiac vascular, orthopedic clean( without implantation of foreign material), orthopedic all other, cesarean delivery, hysterectomy, gastroduodenal, biliary, breast and hernia.
8

Cefotetan or Cefoxitin 1-2g intravenously for appendectomy. Neomycin sulphate plus Erythromycin base 1-2 g of each agent given orally at 19,18, and 9 hours before surgery or Cefotetan or Cefoxitin 1-2g intravenously.

19. Syphilis: 2.4 million units of Procaine Penicillin G intramuscularly or Azithromycin 1g as a single dose is also effective in individuals exposed to infected partners. Ceftriaxone and tetracyclines may be effective incubating syphilis. 20. Travelers Diarrhea: Avoidance of fresh food and water sources that are likely to be contaminated is recommended for travelers to developing countries where diarrhea is endemic. Prophylaxis is recommended for those with significant underlying disease( Inflammatory bowel disease, AIDS, Diabetes, Heart disease in elderly, conditions requiring immunosuppressive medications). Prophylaxis is started upon entery into the destination country and is continued for 1 or 2 days after leaving. Bismith subsalicylate is effective but it turns the tongue and stools black and can interfere with doxycycline absorption which may be needed for malaria prophylaxis. Once daily Norfloxacin 400mg, Ciprofloxacin 500mg, Ofloxacin 300mg or Trimethoprim-sulfamethoxazole 160/800 are recommended prophylactic agents. 21. Urinary tract infection: Prophylactic antibiotic therapy is given to prevent recurrence after treatment of UTIs. Women who have more than three episodes of cystitis per year are considered candidates for prophylaxis.Single dosing of Trimethoprimsulfamethoxazole(40mg/200mg), nitrofurantoin(100mg) and cephalexin(250mg) at bed time or at the time of intercourse

References:

Current Medical Diagnosis and Treatment (Lawrence M.Tierney,Jr., Stephen J.Mcphee) Moore DAJ et al: African trypanosomiasis. Curr Pharm Des 2002;88:74. DixonTC et al:Anthrax. N Engl J Med 1999;341:815. Mederos I et al: Antibiotic Prophylaxis for mammalian bites,Cochrane Database Syst Rev 2001 Cumming J et al: Objective estimates of the incidence and consequences of multiple organ dysfunction and sepsis after burn trauma2001;50:510. Bayers AS et al: Diagnosis and management of infective endocarditis and its complications, circulation 1998;98:2936. Vlachogiannakos J et al: Review article: primary prophylaxis for portal hypertensice bleeding in cirrhosis.Ailment Pharmacol Ther 2000;14:851. Internet

10