When the infecting organism has been identified, specific therapy is chosen as follows. Intravenous administration should continue until the patient is capable of taking drugs by mouth, and whether continuation therapy should be given by mouth or i.v. is a matter of debate. Antimicrobials (except aminoglycosides) enter well into the CSF when the meninges are inflamed; relapse may be due to restoration of the blood-CSF barrier as inflammation is reduced. The following are recommended (adult doses).
Neisseria meniningitidis: benzylpenicillin 2.4 g 4-6-hourly or cefotaxime 2-3 g 6-8-hourly is given. Treatment should continue for a minimum of 5 days.
Streptococcus pneumoniae: cefotaxime 2-3 g 6-8-hourly is given or benzylpenicillin 2.4 g 4-6-hourly if the organism is penicillin-sensitive. Treatment should continue for 10 days after the patient has become afebrile and the physician should be aware of the possibility of relapse.
Haemophilus influenzae: cefotaxime 2-3 g 6-8-hourly or chloramphenicol 100 mg/kg/d is given. Treatment should continue for 10 days after the temperature has settled. Subdural empyema, often presenting as persistent fever, is relatively common after haemophilus meningitis and may require surgical drainage.
The three common pathogens (below) are spread by respiratory secretions. Asymptomatic nasopharyngeal carriers seldom develop meningitis but they may transmit the pathogens to close personal contacts. Rifampicin by mouth is effective at reducing carriage rates.
Meningococcal meningitis often occurs in epidemics in closed communities, but also in isolated cases. Close personal contacts should receive oral rifampicin 600 mg 12-hourly for 2 days. Single doses of oral ciprofloxacin (500 mg) or i.m. ceftriaxone (2 g) are alternatives, the latter of particular value for pregnant women.
Haemophilus influenzae type b has an infectivity similar to that of the meningococcus. Rifampicin 600 mg daily should be given for 4 days.
Pneumococcal meningitis tends to occur in isolated cases and chemoprophylaxis of contacts is not recommended.
(For Helicobacter pylori see p. 630.) Antimicrobial therapy should be reserved for specific conditions with identified pathogens where benefit has been shown; not all acute diarrhoea is infective for it can be caused by bacterial toxins in food, dietary indiscretions, anxiety and by drugs. Even if diarrhoea is infective, it may be due to viruses; or, if it is bacterial, antimicrobial agents may not reduce the duration of symptoms and may aggravate the condition by permitting opportunistic infection and encouraging Clostridium difficile associated diarrhoea. Maintenance of water and electrolyte balance, either by i.v. infusion or orally with a glucose-electrolyte solution together with an anti-motility drug (except in small children) are the mainstays of therapy in such cases (see Oral rehydration therapy, p. 643).
Some specific intestinal infections do benefit from chemotherapy:
Campylobacter jejuni. Erythromycin or ciprofloxacin by mouth will eliminate the organism from the stools and a 5-day course is worth giving early in the illness if it is severe.
Shigella. Mild disease requires no specific antimicrobial therapy but toxic shigellosis with high fever should be treated with ciprofloxacin or amoxicillin by mouth.
Salmonella. An antimicrobial should be used for severe salmonella gastroenteritis, or for bacteraemia or salmonella enteritis in an immunocompromised patient. The choice lies between ciprofloxacin, amoxicillin or co-trimoxazole, according to the sensitivity of the pathogen.
Typhoid fever is a generalised infection and requires treatment with ciprofloxacin. Chloramphenicol, amoxicillin or co-trimoxazole are less effective alternatives. The i.v. route should be used at least initially, followed by oral administration. A longer period of treatment may be required for those who develop complications such as osteomyelitis or abscess.
A carrier state develops in a few individuals who have no symptoms of disease but who can infect others.7 Organsims reside in the biliary or urinary tracts. Ciprofloxacin in high dose by mouth for 3-6 months may be successful for what can be a very difficult problem. Cholecystectomy or investigation of urinary tract abnormalities may be needed.
Escherichia coli is a normal inhabitant of the bowel but some enterotoxigenic strains are pathogenic and are frequently a cause of travellers' diarrhoea. A quinolone, e.g. ciprofloxacin, is the drug of choice in most high-risk parts of the world for a severe attack (see Travellers' diarrhoea, p. 644). Antimicrobials are not generally given for prophylaxis but, when it is indicated, a quinolone should be used.
Verotoxic Escherichia coli (VTEC; 0157) may cause severe bloody diarrhoea and systemic effects such as the haemolytic uraemic syndrome (HUS); antibiotic therapy has been shown in some trials to worsen the prognosis, perhaps by releasing more toxin from dying bacteria. An antimicrobial should generally therefore be avoided for bloody diarrhoea unless the diagnosis has been confirmed bacte-riologically not to be VTEC.
Vibrio cholerae. The cause of death in cholera is electrolyte and fluid loss in the stools and this may exceed 11/h. The most important aim of treatment is prompt replacement and maintenance of water and electrolytes with oral or intravenous electrolyte solutions. Doxycycline, given early, significantly reduces the amount and duration of diarrhoea and eliminates the organism from the faeces (thus lessening the contamination of the environment). Carriers may be treated by doxycycline by mouth in high dose for 3 days. Ciprofloxacin may be given for resistant organisms.
7 The most famous carrier was Mary Mallon ('Typhoid Mary') who worked as a cook in New York City, USA, using various assumed names and moving through several different households. She caused at least 10 outbreaks with 51 cases of typhoid fever and 3 deaths. To protect the public, she was kept in detention for 23 years.
Suppression of bowel flora is thought by some to be useful in hepatic encephalopathy. Here, absorption of products of bacterial breakdown of protein (ammonium, amines) in the intestine lead to cerebral symptoms and even to coma. In acute coma, neomycin 6 g/d should be given by gastric tube; as prophylaxis, 1-4 g/d may be given to patients with protein intolerance who fail to respond to dietary protein restriction (see also lactulose, p. 640).
Selective decontamination of the gut reduces the risk of nosocomial infection from gut organisms (including fungi) in patients who are immunocompromised or receiving intensive care (notably mechanical ventilation). The commonest regimen involves combinations of nonabsorbable (framy-cetin, colistin, nystatin and amphotericin) and i.v. (cefotaxime) antimicrobials to reduce the number of Gram-negative bacilli and yeasts while maintaining a normal anaerobic flora. An alternative is to administer oral ciprofloxacin alone.
Peritonitis is usually a mixed infection and antimicrobial choice must take account of coliforms, anaerobes and streptococci; a combination of gentamicin, benzylpenicillin plus metronidazole or of cefuroxime plus metronidazole, or meropenem alone is usually appropriate. Surgical drainage of peritoneal collections and abscesses is usually required as well.
Chemoprophylaxis in surgery: see p. 208. Antibiotic-associated colitis: see p. 210.
Infection of the urinary tract
(excluding sexually transmitted infections) Common pathogens include:
• Escherichia coli (commonest in all patient groups)
• Other Enterobacteriaceae
• Pseudomonas aeruginosa
• Enterococcus spp.
• Staphylococcus saprophyticus.
Patients with abnormal urinary tracts (e.g. renal stones, prostatic hypertrophy, indwelling urinary catheters) are likely to be infected with a more varied and antimicrobial-resistant microbial flora. Identification of the causative organism and of its sensitivity to drugs are important because of the range of organisms and the prevalence of resistant strains.
For infection of the lower urinary tract a low dose may be effective, as many antimicrobials are concentrated in the urine. Infections of the substance of the kidney require the doses needed for any systemic infection. Elimination of infection is hastened by a large urine volume (over 1.5 1/d) and by frequent micturition.
Drug treatment of urinary tract infection falls into several categories:
Initial treatment with an oral cephalosporin (e.g. cefalexin), trimethoprim, amoxicillin or co-amoxiclav is usually satisfactory, although current resistance rates of 20-50% among common pathogens for trimethoprim and amoxicillin threaten their value for empirical therapy. Therapy should normally last 3 days and may need to be altered once the results of bacterial sensitivity are known.
Acute pyelonephritis may be accompanied by septicaemia and it is advisable to start with gentamicin plus amoxicillin i.v. or alternatively cefotaxime i.v. alone. If oral therapy is considered suitable, ciprofloxacin or norfloxacin is recommended for 2 weeks. This is an infection of the kidney substance and so needs adequate blood as well as urine concentrations.
Attacks following rapidly with the same organism may be relapses and indicate a failure to eliminate the original infection. Attacks with a longer interval between them and produced by differing bacterial types may be regarded as due to reinfection, most often by ascending infection from the perineal skin. Repeated short courses of antimicrobials should overcome most recurrent infections but, if these fail,
7-14 days of high-dose treatment may be given, following which continuous low-dose prophylaxis may be needed.
Asymptomatic infection ('asymptomatic bacteriuria')
This may be found by routine urine testing of pregnant women or patients with known structural abnormalities of the urinary tract. Such infection may explain micturition frequency or incontinence in the elderly. Appropriate antimicrobial therapy should be given, chosen on the basis of susceptibility tests, and normally for 7-10 days. Amoxicillin or a cephalosporin is preferred in pregnancy, although nitrofurantoin may be used if imminent delivery is not likely (see below).
The commonest pathogens here are Gram-negative aerobic bacilli, although Chlamydia may also be involved. A quinolone such as ciprofloxacin is commonly used, although trimethoprim or erythromycin are also effective. Being lipid soluble, these drugs penetrate the prostate in adequate concentration; they may usefully be combined. Response to a single, short course is often good, but recurrence is common and a patient can be regarded as cured only if he has been symptom-free without resort to antimicrobials for a year. Four weeks of oral therapy is often given for recurrent attacks.
Chemoprophylaxis is sometimes undertaken in patients liable to recurrent attacks or acute exacerbations of ineradicable infection. It may prevent progressive renal damage in children who are found to have asymptomatic bacteriuria on routine screening. Nitrofurantoin (50-100 mg/d), nalidixic acid (0.5-1.0 g/d) or trimethoprim (100 mg/d) are satisfactory. The drugs are best given as a single oral dose at night.
Tuberculosis of the genitourinary tract is treated on the principles described for pulmonary infection (p. 249).
Was this article helpful?