Prophylactic Use of Antimicrobials

PROPHYLACTIC USE OF ANTIMICROBIALS

This refers to the use of AMAs for preventing the setting in of an infection or suppressing contacted infection before it becomes clinically manifest. AMAs are frequently given prophylactically, but in a number of circumstances this is at best wasteful if not harmful. The difference between treating and preventing infections is that treatment is directed against a specific organism infecting an individual patient, while prophylaxis is often against all organisms capable of causing infection. The valid as well as improper prophylactic uses may be categorized as:

1. Prophylaxis Against Specific Organisms

In general highly satisfactory; the choice of drug is clearcut.

(a) Rheumatic fever: group A Streptococci: long acting penicillin G is the drug of choice for preventing recurrences.

(b) Tuberculosis: Children, HIV positive and other susceptible contacts of open cases: Isoniazid alone or with rifampin is recommended.

(c) Mycobacterium avium complex (MAC): HIV/ AIDS patients with low CD4 count may be protected against MAC infection by azithromycin/ clarithromycin.

(d) HIV infection: Health care workers exposed to blood by needle stick injury: zidovudine + lamivudine ± indinavir. Offspring of HIV positive woman can be protected by zidovudine given to pregnant mother and then to the newborn for 6 weeks.

(e) Meningococcal meningitis: during an epidemic, especially in contacts; rifampin/ sulfadiazine/ceftriaxone may be used.

(f) Gonorrhoea/syphilis: before or immediately after contact: ampicillin/ceftriaxone.

(g) Recurrent genital herpes simplex: Acyclovir prophylaxis may be given when four or more recurrences occur in a year.

(h)Malaria: for travellers to endemic areas with high transmission rate: chloroquine/mefloquine.

(i) Influenza A₂ : during an epidemic, especially in contacts: amantadine.

(j) Cholera: tetracycline prophylaxis may be given to close contacts of a case.

(k) Whooping  cough:  non-immunized  child contact during the incubation period: erythromycin can abort clinical disease.

(l) Plague: contacts curing an epidemic: doxycycline.

(m)Pneumocystis jiroveci pneumonia: Transplant recipients on immunosuppressants/leukaemia/ AIDS patients may be protected by cotrimoxazole.

2. Prevention Of Infection In High Risk Situations

It may be valid and satisfactory in certain situations, but controversial in others.

(a)Dental extraction, tonsillectomy, endoscopies cause damage to mucosa harbouring bacteria → bacteremia occurs. In patients with valvular defects, this can cause endocarditis: appropriate prophylaxis with amoxicillin or clindamycin may be given few hours before to few hours after the manipulation.

(b)Catheterization or instrumentation of urinary tract: cotrimoxazole or norfloxacin. Patients with valvular lesions may be protected with ampicillin, gentamicin or vancomycin during catheterization.

(c)To prevent recurrences of urinary tract infection in patients with abnormalities of the tract: cotrimoxazole or nitrofurantoin may be given on a long-term basis since the organism mostly is E. coli.

(d)Chronic obstructive lung disease, chronic bronchitis: ampicillin/doxycycline/ciprofloxacin has been used to prevent acute exacerbations: but are of doubtful value.

(e)Immunocompromized patients (receiving corticosteroids or antineoplastic chemotherapy, neutropenic patients): penicillin/cephalosporin ± an aminoglycoside or fluoroquinolone are often used to prevent respiratory tract infections and septicaemia, but incidence of superinfections is high.

Prophylaxis Of Surgical Site Infection

Surgical site infection (SSI) includes superficial incisional infections (e.g. stitch abscess), deep incisional infection (of soft tissue) and organ/ space infection. The purpose of surgical prophylaxis is to reduce the incidence of SSI with minimal alteration of normal microbial flora of the host and minimal adverse effects.

For grading the need and intensity of antimicrobial prophylaxis, the operative wounds have been classified into 4 categories with increasing risk of SSI (see box).

Wound infection occurs due to microbial contamination of the surgical site. It is important for the surgeon to see that the wound left after surgery does not get infected. Use of sterile instruments, cross-infection control measures (antiseptic/disinfectant, etc.) and good surgical technique to minimise tissue damage, haematoma and devascularization are the primary, and often the only, measures needed. However, extensive, prolonged and often combined use of AMAs is made for prophylaxis of infection after practically all surgeries. Such misuse is particularly rampent in developing countries, probably because of unreliability of infection control measures. The SSI is directly related to the number of bacteria present in the surgical wound at the time of closure. Systemic antimicrobial prophylaxis should be employed only when there is clear risk of SSI. In general, it is not required for clean surgery, except in patient at special risk. Clean surgery in otherwise healthy subjects is associated with very low risk of SSI.

Incidence of postoperative infection is higher when surgery had lasted 2 hours or more. Prophylaxis should be given for surgeries in which a prosthesis is inserted into the bone or soft tissue. Even clean surgery needs to be covered by AMA in diabetics, corticosteroid recipients and other immunocompromised subjects, infants, elderly, malnourished and when there is extensive tissue handling/use of electrocautery, etc.

The selection of drug, dose, timing and duration of prophylactic medication is crucial. It is important that the antibiotic is not started prematurely and is not continued beyond the time when bacteria have access to the surgical wound. Administration of the AMA has to be so timed that peak blood levels occur when clot is forming in the surgical wound, and it is present throughout the procedure. Thus, most of the oral drugs are given 1 hour before incision, while i.v. administration just before/after anaesthesia best ensures effective blood levels of the AMA during surgery. Most AMAs do not penetrate the clot once it is formed and is older than 3 hours. Thus, late and prolonged presence of the antibiotic in circulation serves no purpose, but can foster resistant organisms. In case of prolonged surgery, the AMA may be repeated i.v. during the procedure. Postoperative administration of the AMA, especially after 4 hours of wound closure is recommended only in case of contaminated and dirty surgery, in which case it may be given for upto 5 days.

To be maximally effective, a relatively high dose of the AMA is selected which yields peak blood level several times higher than MIC for the likely pathogens. The drug or combination of drugs is selected based on the knowledge of the organism most commonly causing SSI in a given procedure. Local patterns of wound infection (e.g. prevalence of MRSA) and sensitivities of the causative organisms should guide the selection. The commonly employed AMAs for prophylaxis in case of clean and clean-contaminated surgeries are listed in the box.

Dirty contaminated wounds (including road side accidents): The antimicrobial regimens generally administered for 5 days in case of contaminated dirty wounds are:

1. Cefazolin 1 g i.v. 8 hourly + vancomycin 1 g i.v. 12 hourly

2. Cefoxitin 1 g i.v. 6 hourly/ceftizoxime 1 g i.v. 12 hourly.

3. Clindamycin 0.6 g i.v. 8 hourly + Gentamicin 80 mg i.v. 8 hourly.

4. Ampicillin 2 g i.v. 6 hourly/vancomycin 1 g i.v. 12 hourly + Gentamicin 80 mg i.v. 8 hourly + Metronidazole 0.5 g i.v. 8 hourly.

5. Amoxicillin 1 g + Clavulanate 0.2 g i.v. 12 hourly.

_{* All given for 5 days}.

3. Prevention Of Infection In General

This is highly unsatisfactory in most cases and must be condemned. Examples are:

·          Neonates, especially after prolonged or instrumental delivery.

·          To prevent postpartum infections in the mother after normal delivery.

·          Viral upper respiratory tract infections: to prevent secondary bacterial invasion.

·          To prevent respiratory infections in unconscious patients or in those on respirators.

Antimicrobial prophylaxis in these situations may be hazardous—infection by resistant organisms, fungal and other superinfections can occur, because it is not possible to prevent all infections, at all times, in all individuals.