Methods for using antibiotics

Antibiotics for treating established infection call for little comment, and are described in many places in these manuals. Antibiotics to prevent infection need to be used wisely, in ways in which their benefits outweigh their risks. An operation site which has no bacteria in it to start with can become contaminated with bacteria from:

(1) Outside the patient, in which case they will probably be staphylococci. Preventing such infection is the purpose of the ordinary aseptic routines, and prophylactic antibiotics are no substitute for it. Most surgical patients do not need antibiotic cover for sepsis of this kind. The only absolute indication for it is to cover the implantation of prostheses, which you are unlikely to do.

(2) Inside a patient, when you operate on his large gut or his lower urinary tract, or on a woman's genital tract.

When you use antibiotics prophylactically, aim to provide a concentration in the patient's blood that will kill any bacteria introduced into his wound at the time of the operation. If you want to minimize the risk of peritonitis, he will need protection against enterobacteria (mostly Esch. coli), as well as aerobic and anaerobic streptococci. He will also need protection against bacterioides, and clostridia.

The accepted ways to give antibiotics are:

(1) To give them perioperatively, so that high concentrations are reached in a patient's wound at the time of surgery. Give them intravenously with the premedication, and for 24 to 48 hours only afterwards, unless there is some good reason for continuing them. Starting them a day or more before the operation, or continuing them unnecessarily afterwards, promotes the selection of resistant organisms and the risk of side-effects.

(2) To instil them into the peritoneum after the pus from peritonitis has been washed out. Tetracycline is very effective in preventing postoperative sepsis in the peritoneum, and in the wound in the abdominal wall.

There are several unacceptable methods: (1) Don't put topical antibiotics into a patient's wound. (2) Don't give them by mouth in the hope of ''sterilizing his large gut'[md]systemic antibiotics are probably at least as effective, and safer.

As to the antibiotics to use, you will see from the list of indications below that, if chloramphenicol is not much used in the community, chloramphenicol with metronidazole is likely to be the most cost-effective combination. Otherwise, give cephradine (or some other cephalosporin) with metronidazole. These are certainly much better than one commonly used alternative, which is penicillin and streptomycin.

Try to separate prophylaxis from treatment. For prophylaxis give chloramphenicol, or a cephalosporin with metronidazole. For treatment give gentamicin and metronidazole.

Barker EM, ''Rectal adminstration of metronidazole in severely ill patients', British Medical Journal 1983;287:311[nd]313.[-3] Keighley MRB, ''Perioperative antibiotics', British Medical Journal, 1983;286:1844[nd]1846. THE DOSE AND THE TIMING ARE CRITICAL GET ADEQUATE LEVELS AT THE TIME OF SURGERY

ANTIBIOTICS PERIOPERATIVE PROHPHYLAXIS INDICATIONS. (1) Peritonitis. (2) Any operation which is likely to contaminate a patient's peritoneal cavity, especially large bowel surgery. Use a combination of metronidazole with either an aminoglycoside (such as gentamicin), or a cephalosporin, or, to save cost, chloramphenicol. (3) An operation on his urinary tract when his urine is already contaminated, including bouginage, cystoscopy, and Freyer's prostatectomy. Use an aminoglycoside (gentamicin), a cephalosporin (cephradine), or chloramphenicol. (4) Hysterectomy: as (2). (4) Emergency Caesarean section.

Balance cost and benefit. The instillation of tetracycline solution into the peritoneum (see below) may be comparatively expensive; but if it saves another operation for a residual abscess it is cheap.

CAUTION ! Gentamicin and other aminoglycosides may seriously prolong the action of long-acting (non-depolarizing) relaxants (A 14.3), and may prevent the establishment of spontaneous ventilation. Avoid them unless your anaesthetist is experienced.

CONTRAINDICATIONS. Antibiotics are not needed for: (1) Already well localized infections. (2) Hernias, ovarian cysts, etc.

Disputed indications include elective Caesarean section and appendicectomy.

DOSE. Give two intravenous doses of two suitable antibiotics, one of which is active against aerobic organisms, and the other against anaerobes. Give the first dose intravenously with the premedication. You are only giving two doses, so it is safe to use large ones. Give the second dose 6 hours later. If you are using a tourniquet, time the injection to give the maximum concentration about the time that you release it, so that the clot which forms in the wound will be heavily loaded with drug.

For the aerobic organisms, give: chloramphenicol, or gentamicin, or a cephalosporin, or trimethoprim. Gentamicin is the most potent, but also the most expensive.

For anaerobes, particularly bacterioides give metronidazole. Chloramphenicol is also active, but is less effective.

PARTICULAR ANTIBIOTICS BENZYLPENICILLIN (penicillin G) can be given by several routes. 600 mg is one megaunit (M).

Intramuscularly. Adults, 300 to 600 mg 2 to 4 times in 24 hours. Child up to 12 years 10-20 mg/kg/24 hours. Neonate 30 mg/kg/24 hours.

By intravenous infusion. Adults, up to 24 g in 24 hours. Give it intermittently into a drip. Or give it into an intravenous drip or through a Gordh needle or disposable cannula (''Venflon'), flushed through with 1000 units of heparin.

By intrathecal injection. Adults, 6 to 12 mg in 24 hours.

METRONIDAZOLE, for anaerobic infections Adults, by mouth, 400 mg 8-hourly. By rectum 1 g 8-hourly for 3 days, then 1 g every 12 hours. By intravenous infusion, 500 mg 8-hourly for up to 7 days. Children, any route, give 7.5 mg/kg 8-hourly.

If a patient is seriously ill, give 500 mg (100 ml of 0.5% solution) intravenously as a loading dose over 45 minutes. Preferably give another similar dose 8 hours later. At the same time give a 1 g suppository 8-hourly. For perioperative prophylaxis (as for an emergency Caesarean section or large gut resection) continue for 24 to 48 hours. For peritonitis continue for 5 days.

If you don't have adequate supplies of intravenous metronidazole, you may be able to give it orally, or by suppository, or as an ordinary tablet rectally (1 g 6 to 8- hourly), before and after the operation. Adequate blood levels are not reached for 8 hours after giving a suppository, so start with one, or, better, two intravenous loading doses, and continue with suppositories. Or if you have no intravenous solution, use suppositories only, and start them earlier. It has been suggested that presently accepted doses may be high, and that a 500 mg suppository 12-hourly may be adequate.

CHLORAMPHENICOL. There are several regimes.

Perioperatively. Adults, give 1 g by bolus intravenous injection.

Intravenously. Adults, give an adult 1 g 6-hourly, or 50 mg/kg/24 hours. Child 50 to 100 mg/kg 24 hours in divided doses. Decrease the high dose as soon as clinically indicated. Infant: 50 mg/kg/24 hours in divided doses. Neonate under 2 weeks: 25 mg/kg/24 hours in divided doses. Premature baby: 12.5 to 25 mg/kg/24 hours. In neonates it may cause the ''grey syndrome', but probably not with lower doses.

By mouth. Adults, give 500 mg 6-hourly or 50 mg/kg/24 hours in divided doses for 5 days. Then give 250 mg 4 to 6-hourly for up to 10 days. For children give 25-100 mg/kg/24 hours in divided doses.

In grave emergencies high doses may be justified. Section 31.8 describes a short high dose chloramphenicol regimen for treating typhoid (1 or 2 g 4-hourly for 5 days followed by 250 mg 6-hourly for 14 days). One of the dangers with exceptionally high dosage schemes is that you may come to think of them as normal, and so increase your antibiotic bill unduely.

CAUTION ! (1) Avoid long courses of chloramphenicol. It is among these patients that most cases of aplastic anaemia and leucopenia occur. Their reported incidence in the industrial world is 1:5,000 to 1:10,000 cases. Their incidence is probably lower in non-Caucasians. (2) Avoid intramuscular chloramphenicol; it is poorly absorbed.

CEPHRADINE (other cephalosporins have different doses).

By mouth, 250 to 500 mg 6-hourly. Or, 0.5 to 1.0 g 12-hourly. In children 25 to 50 mg/kg in 24 hours in divided doses.

By intramuscular or intravenous injection, 0.5 to 1 g every 6 hours, increased to 8 g in 24 hours in severe infections. Children 50 to 100 mg in 24 hours in 4 divided doses.

GENTAMICIN. By intramuscular injection or slow intravenous injection or infusion, 2 to 5 mg/kg/24 hours, in divided doses every 8 hours. Children up to 2 weeks give 3 mg/kg every 12 hours. 2 weeks to 12 years give 2 mg/kg every 8 hours.

By intrathecal injection 1 mg in 24 hours, with 2 to 4 mg/kg by intramuscular injection in divided doses every 8 hours.

CAUTION ! In renal impairment the interval between successive doses should be increased.

TRIMETHOPRIM. Adults: by mouth in an acute infection 200 mg 12 hourly. Chronic infections and prophylaxis 100 mg at night. Children: twice daily 2 to 5 months 25 mg, 6 months to 5 years 50 mg, 6 to 12 years 100 mg.

By slow intravenous injection or infusion, 150 to 200 mg 12-hourly. Child under 12 years 6 to 9 mg/kg/24 hours in 3 divided doses.

TETRACYCLINE. Oxytetracycline is likely to be the cheapest preparation. For peritonitis, or contamination of the peritoneal cavity with faeces, wash out the pus or faeces with saline until the fluid comes away clear. Then instil 1 g of oxytetracycline in 1000 ml of saline. Close the abdomen without drains.

THE TREATMENT [s7]OF SURGICAL SEPSIS See also particular conditions: peritonitis 6.2, osteomyelitis 7.4, septic arthritis 7.16 etc.

CAUTION ! In any form of sepsis, antibiotics are not a substitute for surgery when this is necessary.

SPREADING PRESUMPTIVE GRAM-POSITIVE SEPSIS when you don't know the sensitivities[md]give chloramphenicol, cephradine, cloxacillin or methicillin.

SERIOUS PRESUMPTIVE ANAEROBIC SEPSIS, especially intra- abdominal sepsis. Give metronidazole, intravenously or as suppositories with a loading dose intravenously (if available). There may be aerobes also, so give chloramphenicol or gentamicin or cephradine in addition. Continue for not more than 5 days.

PELVIC SEPSIS. Chloramphenicol with metronidazole, or cephradine with metronidazole, or, much less satisfactorily, penicillin with streptomycin.

SEVERE SOFT TISSUE WOUNDS. If there is risk of gas gangrene give benzyl penicillin (or erythromycin if the patient is sensitive to penicillin). And give metronidazole.

INFECTED ABDOMINAL WOUNDS. (1) Chloramphenicol or cephradine as above. Or, (2) a megaunit of benzyl penicillin 8- hourly, and intravenous ampicillin 1 g initially, followed by 0.5 g 8-hourly. AND, give metronidazole 500 mg intravenously initially followed by 1 g 8-hourly by rectum for up to 5 days.

''BLIND THERAPY'. For the severely ill patient presumed to have an infection when the nature and sensitivities of the organism are unknown: give chloramphenicol or cephradine or gentamicin, all with metronidazole. Consider giving benzyl penicillin or ampicillin also if the infection is generalized.

ONLY A FEW HIGH RISK PATIENTS NEED PERIOPERATIVE PROPHYLACTIC ANTIBIOTICS Fig. 2-10 FROM WONDER DRUG TO BITTER PILL. The variety of antibiotics potentially available to treat infections may not be inexhaustible. We should use them wisely.