Tài liệu CLINICAL PHARMACOLOGY 2003 (PART 15) pdf

Bacteroides, streptococci or enterococci are likely pathogens and the following combinations are effective: cefuroxime plus metronidazole or gentamicin plus benzylpenicillin plus metroni

Chemotherapy of bacterial

infections

SYNOPSIS

We live in a world heavily populated by

microorganisms of astonishing diversity Most

of these exist in our external environment but

certain classes are normally harboured within

our bodies, especially colonising mucosal

surfaces Depending on the circumstances,

infectious disease can arise from organisms

living exogenously or endogenously, and a

knowledge of common pathogens at specific

sites often provides a good basis for rational

initial therapy.

This chapter considers the bacteria that

cause disease in individual body systems, the

drugs that are used to combat them, and how

they are best used It discusses infection of:

Blood

Paransal sinuses and ears

Throat

Bronchi, lungs and pleura

Endocardium

Meninges

Intestines

Urinary tract

Genital tract

Bones and joints

Eye

Also mycobacteria, that infect many sites

Table I I I (p 21 I) is a general reference for

this chapter.

Infection of the blood

Septicaemia is a medical emergency Accurate

microbiological diagnosis is of the first importance and blood cultures should be taken before starting antimicrobial therapy Usually, the infecting organ-ism^) is not known at the time of presentation and treatment must be instituted on the basis of a 'best guess' The clinical circumstances may provide some clues Patients who have been in hospital for some time before presenting with septicaemia may need antibiotic regimens that provide more reliable

cover for multiply resistant pathogens, and examples

of suitable choices are given in the list below in brackets.

• When septicaemia follows gastrointestinal or

genital tract surgery, Escherichia coll (or other

Gram-negative bacteria), anaerobic bacteria, e.g

Bacteroides, streptococci or enterococci are likely

pathogens and the following combinations are effective: cefuroxime plus metronidazole or gentamicin plus benzylpenicillin plus metronidazole (meropenem plus vancomycin)

• Septicaemia related to urinary tract infection

usually involves Escherichia coli (or other

Gram-negative bacteria), enterococci: gentamicin plus benzylpenicillin or cefotaxime alone

(ciprofloxacin plus vancomycin)

• Neonatal septicaemia is usually due to streptococci or coliforms: benzylpenicillin plus gentamicin

• Staphylococcal septicaemia may be suspected

where there is an abscess, e.g of bone or lung, or

with acute infective endocarditis or infection of

intravenous catheters: high dose flucloxacillin is

indicated (vancomycin)

• Toxic shock syndrome occurs in circumstances that

include healthy women using vaginal tampons,

abortion or childbirth, and occasionally with skin

and soft tissue infection The clinical problem is

due to systemic effects of toxins produced by

staphylococci: while this is not strictly an infection

of the blood, flucloxacillin is used to eliminate the

source Elimination of the source by removal of the

tampon and drainage of abscesses, and circulatory

support are also important

Antimicrobials should be given i.v initially in

septicaemia

OTITIS MEDIA

Mild cases, characterised by pinkness or infection

of the eardrum, often resolve spontaneously and need only analgesia and observation They are nor-mally viral A bulging, inflamed eardrum indicates

bacterial otitis media usually due to Streptococcus pneumoniae, Haemophilus influenzae, Moraxella (Bran-hamella) catarrhalis, Streptococcus pyogenes (Group A)

or Staphylococcus aureus Amoxicillin or co-amoxiclav

is satisfactory, but the clinical benefit of antibiotic therapy is very small when tested in controlled trials Chemotherapy has not removed the need for myringotomy when pain is very severe, and also for later cases, as sterilised pus may not be completely absorbed and may leave adhesions that impair hearing Chronic infection presents a similar problem

to that of chronic sinus infection, above

Infection of paranasal

sinuses and ears

SINUSITIS

Acute infection of the paranasal sinuses causes

significant morbidity Since oedema of the mucous

membrane hinders the drainage of pus, a logical

first step is to open the obstructed passage with a

sympathomimetic vasoconstrictor, e.g ephedrine

nasal drops Antibiotic therapy produces limited

additional clinical benefit, but the common infecting

organism—Streptococcus pneumoniae, Haemophilus

influenzae, Streptococcus pyogenes, Moraxella

(Branha-mella) catarrhalis—usually respond to oral amoxicillin

(with or without clavulanic acid) or doxycycline,

if the case is serious enough to warrant antibiotic

therapy

In chronic sinusitis, correction of the anatomical

abnormalities (polypi, nasal septum deviation) is

often important Very diverse organisms, many of

them normal inhabitants of the upper respiratory

tract, may be cultured, e.g anaerobic streptococci,

Bacteroides spp., and a judgement is required as

to whether any particular organism is acting as a

pathogen Choice of antibiotic should be guided by

culture and sensitivity testing; therapy may need to

be prolonged

Infection of the throat

Pharyngitis is usually viral but the more serious

cases may be caused by Streptococcus pyogenes (Group

A) which is always sensitive to benzylpenicillin Unfortunately, streptococcal sore throats cannot be clinically differentiated from non-streptococcal with any certainty Prevention of complications is more important than relief of the symptoms which seldom last long There is no general agreement whether chemotherapy should be employed in mild sporadic sore throat and expert reviews on the subject reflect the resulting diversity of clinical views.1'2-3 The disease usually subsides in a few days, septic complications are uncommon and rheumatic fever rarely follows It is reasonable to withhold penicillin unless streptococci are cultured

or the patient develops a high fever Severe spora-dic or epidemic sore throat is likely to be

strepto-1 Cooper R J, Hoffman J R, Bartlett J G et al 2001 Principles of appropriate antibiotic use for acute pharyngitis in adults: background Annals of Internal Medicine 134: 506.

2 Del Mar C B, Glasziou P P, Spinks A B 2001 Antibiotics for sore throat (Cochrane Review) The Cochrane Library 2 Oxford: Update Software.

3 Thomas M, Del Mar C, Glasziou P 2000 How effective are treatments other than antibiotics for acute sore throat? British Journal of General Practice 50: 817.

I N F E C T I O N O F T H E B R O N C H I , L U N G S A N D P L E U R A

coccal and phenoxymethylpenicillin by mouth (or

erythromycin/clarithromycin or an oral

cephalo-sporin in the penicillin allergic) should be given to

prevent these complications Ideally, it should be

continued for 10 days, but compliance is bad once

the symptoms have subsided and 5 days should be

the minimum objective If there is a possibility that

the pharyngitis is due to infectious mononucleosis,

amoxicillin must not be used as the patient is very

likely to develop a rash (see p 220) In a closed

com-munity, chemoprophylaxis of unaffected people to

stop an epidemic may be considered, for instance

with phenoxymethylpenicillin 125 mg 12-hourly

orally, for a period depending on the course of the

epidemic

In scarlet fever and erysipelas, the infection is

invariably streptococcal (Group A) and

benzyl-penicillin should be used even in mild cases, to

prevent rheumatic fever and nephritis

Chemoprophylaxis

Chemoprophylaxis of streptococcal (Group A)

infection with phenoxymethylpenicillin should be

undertaken in patients who have had one attack of

rheumatic fever It is continued for at least 5 years,

or until aged 20, whichever is the longer period

(although some hold that it should continue for life,

for histological study of atrial biopsies shows that

the cardiac lesions may progress despite absence of

clinical activity) Chemoprophylaxis should be

continued for life after a second attack of rheumatic

fever A single attack of acute nephritis is not an

indication for chemoprophylaxis but in the rare

cases of nephritis in which recurrent haematuria

occurs after sore throats, chemoprophylaxis should

be used Ideally, chemoprophylaxis should continue

throughout the year but, if the patient is unwilling

to submit to this, at least the colder months should

be covered (see also p 207)

Adverse effects are uncommon Patients taking

penicillin prophylaxis are liable to have

penicillin-resistant viridans type streptococci in the mouth, so

that during even minor dentistry, e.g scaling, there

is a risk of bacteraemia and thus of infective

endo-carditis with a penicillin-resistant organism in those

with any residual rheumatic heart lesion The same

risk applies to urinary, abdominal and chest

surg-ery, and patients need special chemoprophylaxis (see Endocarditis) Patients taking penicillins are also liable to be carrying resistant staphylococci and pneumococci

Other causes of pharyngitis

Vincent's infection (microbiologically complex,

inc-ludes anaerobes, spirochaetes) responds readily to benzylpenicillin; a single i.m dose of 600 mg is often enough except in a mouth needing dental treatment, when relapse may follow Metronidazole

200 mg 8-hourly by mouth for 3 days is also effective

Diphtheria (Corynebacterium diphtheriae) Antitoxin

10 000-100 000 units i.v in two divided doses 0.5-2 h apart is given to neutralise toxin already formed according to the severity of the disease Erythromycin or benzylpenicillin is also used, to prevent the production of more toxin by destroying the bacteria

Whooping-cough (Bordetella pertussis)

Chemother-apy is needed in children who are weak, have damaged lungs or are under 3 years old Erythro-mycin is usually recommended at the catarrhal stage and should be continued for 14 days (also as prophylaxis in cases of special need) It may curtail

an attack if given early enough (before paroxysms have begun) but is not dramatically effective; it also reduces infectivity to others A corticosteroid, salbu-tamol, and physiotherapy may be helpful for relief

of symptoms, but reliable evidence of efficacy is lacking

Infection of the bronchi, lungs and pleura

BRONCHITIS

Most cases of acute bronchitis are viral; where bacteria are responsible the usual pathogens are

Streptococcus pneumoniae and/or Haemophilus influ-enzae It is questionable if there is role for

anti-microbials in uncomplicated acute bronchitis but

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amoxicillin, a tetracycline or trimethoprim are

app-ropriate if treatment is considered necessary

In chronic bronchitis, suppressive chemotherapy,

generally needed only during the colder months (in

temperate, colder regions), may be considered for

patients with symptoms of pulmonary insufficiency,

recurrent acute exacerbations or permanently

puru-lent sputum Amoxicillin or trimethoprim is

suit-able for treatment

For intermittent therapy, the patient is given a

supply of the drug and is told to take it in full dose

at the first sign of a 'chest' cold, e.g purulent

sputum, and to stop it after 3 days if there is rapid

improvement Otherwise, the patient should

conti-nue the drug until recovery takes place If the

exacerbation lasts for more than 10 days, there is a

need for clinical reassessment

PNEUMONIAS

The clinical setting is a useful guide to the causal

organism and hence to the 'best guess' early choice

of antimicrobial, although in seriously ill patients

cover for both 'typical' and 'atypical' pathogens

should be included from the beginning It is not

possible reliably to differentiate between pneumonias

caused by 'typical' and 'atypical' pathogens on

clinical grounds alone

Pneumonia in previously healthy people

(community acquired)

Disease that is segmental or lobar in its

distribu-tion is usually caused by Streptococcus pneumoniae

(pneumococcus) Haemophilus influenzae is a rare

cause in this group, although it more often leads to

exacerbations of chronic bronchitis and does cause

pneumonia in patients infected with HIV

Benzyl-penicillin i.v or amoxicillin p.o are the treatments

of choice if pneumococcal pneumonia is very likely;

alternatively, use erythromycin/clarithromycin in a

penicillin-allergic patient Seriously ill patients are

best given benzylpenicillin (to cover the

pneumo-coccus) plus ciprofloxacin (to cover Haemophilus

and 'atypical' pathogens) Where penicillin-resistant

pneumococci are prevalent, i.v cefotaxime is a

reasonable 'best guess' choice

Pneumonia following influenza is often caused

by Staphylococcus aureus, and 'best guess' therapy is

usually achieved by adding flucloxacillin to one of the regimens above When staphylococcal pneumo-nia is proven, sodium fusidate p.o plus flucloxa-cillin i.v should be used in combination

'Atypical' cases of pneumonia may be caused by

Mycoplasma pneumoniae which may be epidemic, or more rarely Chlamydia pneumoniae or psittaci (psitta-cosis/ornithosis) Legionella pneumophilia or Coxiella burnetii (Q fever) and a tetracycline or erythromycin/

clarithromycin should be given by mouth Treatment

of ornithosis should continue for 10 days after the fever has settled and in mycoplasma pneumonia and Q fever a total of 3 weeks treatment may be needed to prevent relapse

At the earliest possible stage, once a clinical

im-provement has been seen, initial i.v administration

of antibiotics for pneumonia should be switched to the oral route

Pneumonia acquired in hospital

Pneumonia is usually defined as being nosocomial

(Greek: nosokomeian, hospital) if it presents after at

least 2 days in hospital It occurs primarily among patients admitted with medical problems or recovering from abdominal or thoracic surgery or

on mechanical ventilators The common pathogens

are Staphylococcus aureus, Enterobacteriaceae, Strepto-coccus pneumoniae, Pseudomonas aeruginosa, and Haemophilus influenzae It is reasonable to initiate

therapy with ciprofloxacin, meropenem or cef-tazidime (plus vancomycin if the local prevalence of MRSA is high) until the results of sputum culture and antimicrobial susceptibility tests are known

Pneumonia in people with chronic lung disease

Normal commensals of the upper respiratory tract

proliferate in damaged lungs especially following viral infections, pulmonary congestion or pulmonary infarction Mixed infection is therefore common,

and since Haemophilus influenzae and Streptococcus pneumoniae are often the pathogens, amoxicillin

or trimethoprim are reasonable choices, but if

E N D O C A R D I T I S

response is inadequate co-amoxiclav or a quinolone

should be substituted

Klebsiella pneumoniae rarely causes lung infection

(Triedlander's pneumonia') in the alcoholic and

debilitated elderly Abscesses form, particularly in

the upper lobes: cefotaxime possibly with an

amino-glycoside is recommended

Moraxella (previously Branhamella) catarrhalis, a

commensal of the oropharynx, may be a pathogen

in patients with chronic bronchitis; because many

strains produce B-lactamase, co-amoxiclav or

eryth-romycin/clarithromycin should be used

Pneumonia in immunocompromised

patients

Pneumonia is common, e.g in acquired

immuno-deficiency syndrome (AIDS) or in those who are

receiving immunosuppressive drugs

Common pathogenic bacteria may be

respons-ible (Staphylococcus aureus, Streptococcus pneumoniae)

but often organisms of lower natural virulence

(Enterobacteriaceae, viruses, fungi) are causal and

strenuous efforts should be made to identify the

microbe including, if feasible, bronchial washings

or lung biopsy

• Until the pathogen is known the patient should

receive broad-spectrum antimicrobial treatment,

such as an aminoglycoside plus ceftazidime

• Aerobic Gram-negative bacilli, e.g

Enterobacteriaceae, Klebsiella spp., are pathogens

in half of the cases, especially in neutropenic

patients, and respond to cefotaxime or

ceftazidime Pseudomonas aeruginosa may also

cause pneumonia in these patients; for treatment

see Reference data on antimicrobial drugs of

choice, page 211, Table 11.1

• An important respiratory pathogen in patients

with deficits in cell-mediated immunity is the

fungus Pneumocystis carinii, which should be

treated with co-trimoxazole 120 mg/kg/d by

mouth or i.v in 2-4 divided doses for 14 days, or

with pentamidine (see p 276)

Legionnaires' disease

Legionella pneumophila responds to erythromycin

2-4 g/d i.v in divided doses but rifampicin may be

added in more severe infections Ciprofloxacin is also effective

Pneumonia due to anaerobic microorganisms

Pneumonia is often caused by aspiration of material from the oropharynx, or due to the presence of other lung pathology such as pulmonary infarction

or bronchogenic carcinoma As well as conventional microbial causes, the pathogens include anaerobic

and aerobic streptococci, Bacteroides spp and Fuso-bacterium, and the diagnosis may be missed unless

anaerobic cultures of fresh material are performed Treatment for several weeks with cefuroxime plus metronidazole may be needed to prevent relapse

Pulmonary abscess is treated according to the

organism identified and with surgery if necessary

Empyema is treated according to the organism

isolated and with aspiration and drainage

Endocarditis

When suspicion is high enough, three blood cultures should be taken over a few hours and antimicrobial treatment commenced; it can be adjusted later in the light of the results Delay in treating only exposes the patient to the risk of grave cardiac damage or systemic embolism Streptococci, enterococci and staphylococci are causal in 80% of cases, with viridans group streptococci the most common pathogens In intravenous drug users,

Staphylococcus aureus is the most likely organism.

Culture-negative endocarditis (up to 20% of cases)

is usually due to prior antimicrobial therapy or to special culture requirements of the microbe; it is best regarded as being due to streptococci and treated accordingly

PRINCIPLES FORTREATMENT

• High doses of bactericidal drugs are needed because the organisms are difficult to access in avascular vegetations on valves and the protective host reaction is negligible

• Drugs should be given parenterally at least

13

initially and preferably by intravenous bolus

injection which achieves the necessary high peak

concentration to penetrate the relatively

avascular vegetations

• The infusion site should be examined daily and

changed regularly to prevent opportunistic

infection, which is usually with

coagulase-negative staphylococci or fungi Alternatively,

use may be made of a central subclavian venous

catheter sited with meticulous attention to

aseptic technique

• Prolonged therapy is needed, usually 4 weeks,

and in the case of infected prosthetic valves at

least 6 weeks The patient should be reviewed

one month after completing the antimicrobial

treatment Valve replacement may be needed at

any time during and after antibiotic therapy if

cardiovascular function deteriorates or if the

infection proves impossible to control

• Dosage must be adjusted according to the

sensitivity of the infecting organism This is

established by the Minimum Inhibitory

Concentration test (p 203), rather than by testing

dilutions of the patient's serum against the

organism (the Serum Bactericidal Titre which

was formally recommended, but which has not

been proved useful)

DOSE REGIMENS

The following regimens are those commonly

rec-ommended:

1 Initial (best guess) treatment should comprise

benzylpenicillin 1.2-2.4 g 4-hourly, plus

gentamicin in low dose, e.g 80 mg 12-hourly, by

i.v injection (synergy allows this dose of

gentamicin and minimises risk of adverse

effects) Regular serum gentamicin assay is vital:

trough concentrations should be below 1 mg/1

and peak concentrations about 3 mg/1; if

Staphylococcus aureus is suspected, high-dose

flucloxacillin plus either gentamicin or sodium

fusidate should be used Patients allergic to

penicillin should be treated with vancomycin

2 When an organism has been identified and its

sensitivity to drugs determined:

• Viridans group streptococci: benzylpenicillin

plus gentamicin i.v for at least 4 weeks or, if

the organism is very sensitive, for 2 weeks, followed by amoxicillin p.o for 2 weeks Some patients with uncomplicated endocarditis caused by very sensitive strains may be managed as outpatients; for these patients ceftriaxone may be suitable, with its prolonged t1/2 allowing convenient once-daily administration

• Enterococcus faecalis (Group D): benzylpenicillin

1.8-3g 4-hourly plus gentamicin i.v for 4-6 weeks The prolonged gentamicin

administration carries a significant risk of adverse drug reactions, but is essential to assure eradication of the infection

• Staphylococcus aureus: flucloxacillin 2 g 4-hourly

by i.v injection for at least 4 weeks plus either gentamicin by i.v injection or sodium fusidate

by mouth for the first 1-2 weeks

• Staphylococcus epidermidis and other coagulase

negative staphylococci infecting native heart valves should be managed as for

Staphylococcus aureus if the organism is

sensitive These organisms, however, have a predilection for prosthetic valves and such cases should be treated with vancomycin plus rifampicin for at least 6 weeks with

gentamicin for the first 2 weeks

• Coxiella or Chlamydia: tetracycline by mouth

for at least 4-6 weeks Valve replacement is advised in most cases, but some may continue indefinitely on tetracycline

• Fungal endocarditis: amphotericin plus

flucytosine are used Valve replacement is usually essential

• Culture-negative endocarditis: benzylpenicillin

plus gentamicin i.v are given for 4-6 weeks

PROPHYLAXIS

Transient bacteraemia is provoked by dental proce-dures, surgical incision of the skin, instrumentation

of the urinary tract, parturition and even seemingly innocent activities such as brushing the teeth or chewing toffee Experience shows that people with acquired or congenital heart defects are at risk from bacteraemia and may be protected by antimicro-bials used prophylactically (although there is no scientific proof of the efficacy of this) The drugs are given as a short course in high dose at the time of

the procedure to coincide with the bacteraemia and

avoid emergence of resistant organisms There

follow general recommendations4'5'6 on

antimicro-bial prophylaxis; not every contingency is covered

because prophylaxis may be needed for patients

with cardiac defects whenever surgery or

instru-mentation is undertaken on tissue that is heavily

colonised or infected, e.g in surgery or

instrumen-tation of the upper respiratory or genitourinary

tracts, or obstetric, gynaecological or gastrointestinal

procedures Different national Working Parties have

recommended differing prophylactic measures,4'5'6

and the physician should consult special sources

and exercise a clinical judgement that relates to

individual circumstances All oral drugs should be

taken under supervision

Dental procedures

Under local or no anaesthesia

• Adults who are not allergic to penicillins and who

have not taken penicillin more than once in the

previous month (including those with a

prosthetic valve, but not if they have had

endocarditis in the past) should receive

amoxicillin 3 g by mouth 1 h before the

procedure

• Patients allergic to penicillins or who have taken

penicillin more than once in the previous month

should receive clindamycin 600 mg by mouth 1 h

before the procedure

Under general anaesthesia

• Patients who are not allergic to penicillins and

who have not taken penicillin more than once in

the previous month should receive amoxicillin

1 g i.m or i.v at induction then 0.5 g by mouth

6 h later Alternatively amoxicillin 3 g may be

taken by mouth together with probenecid 1 g by

4 Simmons N A1993 Recommendations for endocarditis

prophylaxis Journal of Antimicrobial Chemotherapy 31: 437.

5 Littler W A, McGowan D A, Shanson D C 1997 Changes in

recommendations about amoxycillin prophylaxis for

prevention of endocarditis Lancet 350:1100.

6 Dajani A S, Taubert K Wilson W et al 1997 Prevention of

bacterial endocarditis Recommendations by the American

Heart Association Journal of the American Medical

Association 277:1794.

M E N I N G I T I S

mouth 4 h before the procedure (probenecid delays renal excretion and thus maintains a high blood concentration of amoxicillin), or

amoxicillin 3 g may be followed by another 3 g dose as soon as possible after the procedure

• Special risk patients, i.e with prosthetic valves

or with previous endocarditis, should receive amoxicillin 1 g i.m or i.v and gentamicin 120 mg

at induction, then amoxicillin 0.5 g by mouth 6 h later Patients who are penicillin-allergic or have received penicillin more that once in the

previous month should receive vancomycin 1 g i.v over 100 min then gentamicin 120 mg i.v at induction or 15 min before the procedure; or teicoplanin 400 mg i.v plus gentamicin 120 mg i.v at induction or 15 min before the procedure;

or clindamycin 300 mg over at least 10 min at induction or 15 min before the procedure then clindamycin 150 mg i.v or by mouth 6 h later Special sources should be consulted for pro-phylactic regimens recommended for children and for other procedures, such as instrumentation of the urogenital or gastrointestinal tracts

Meningitis

Speed of initiating treatment and accurate bacterio-logical diagnosis are the major factors determining the fate of the patient When meningococcal disease

is suspected (and unless the patient has a history

of penicillin anaphylaxis) treatment with benzyl-penicillin should be started by the general practi-tioner before transfer to hospital; benefit to the patient outweighs the reduced chance of identi-fying the causative organism Newly introduced diagnostic methods such as the Polymerase Chain Reaction (PCR) for bacterial DNA in CSF or blood enable accurate and rapid diagnosis even when the causative organisms have been destroyed by antibiotics

Drugs must be given i.v in high dose; the regimens below provide the recommended therapy, with alternatives for patients allergic to first choices Intrathecal therapy is now considered unnecessary, and can be dangerous, e.g encephalopathy with penicillin

13

Initial therapy should be sufficient to kill all

pathogens, which are likely to be:

All ages over 5 years

For Neisseria meningitidis and Streptococcus

pneu-moniae benzylpenicillin 2-4 g 4-6-hourly should be

given, followed, in the case of Neisseria meningitidis,

by rifampicin for 2 days prior to discharge from

hospital (to eradicate persisting organisms) Some

prefer to use cefotaxime 2-3 g 6-8-hourly in all cases

until the results of susceptibility tests are known, and

this may be the generally preferred choice if penicillin

resistance in pneumococci and meningococci rises in

prevalence Optimal therapy for penicillin-resistant

pneumococcal meningitis may comprise cefotaxime

2-3 g 6-8-hourly plus vancomycin 1 g 12-hourly plus

rifampicin 600 gm 12-hourly

Children under 5 years

Neisseria meningitidis is now commonest and

Haemo-philus influenzae, formerly a frequent pathogen, is

much less often isolated (as a result of

immunisa-tion programmes) Streptococcus pneumoniae is also

less commonly found than in older patients

Give a cephalosporin, e.g cefotaxime When

Haemophilus influenzae is isolated give rifampicin

for 4 days before discharge from hospital to clear

naso-pharyngeal carriage

Neonates

For Escherichia coli: give cefotaxime or ceftazidime

perhaps with gentamicin For Group B streptococci:

give benzylpenicillin plus gentamicin Consult a

specialist text for details of doses for neonates

Ampicillin must be added if Listeria

monocyto-genes is suspected.

Dexamethasone given i.v and early appears to

reduce long-term neurological sequelae, especially

sensorineural deafness, in infants and children

There is not, however, general agreement about the

use of dexamethasone for meningitis in adults

Chloramphenicol remains a good alternative

for 'blind' therapy in patients giving a history of

B-lactam anaphylaxis

SUBSEQUENTTHERAPY

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 resto-ration 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 4-6-6-8-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

Chemoprophylaxis

The three common pathogens (below) are spread by respiratory secretions Asymptomatic nasopharyn-geal carriers seldom develop meningitis but they may transmit the pathogens to close personal con-tacts Rifampicin by mouth is effective at reducing carriage rates

Meningococcal meningitis often occurs in epi-demics 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

iso-lated cases and chemoprophylaxis of contacts is not

recommended

Infection of the intestines

(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

in-discretions, 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

cipro-floxacin 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

anti-microbial therapy but toxic shigellosis with high

fever should be treated with ciprofloxacin or

amoxi-cillin 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,

amoxi-cillin or co-trimoxazole, according to the sensitivity

of the pathogen

Typhoid fever is a generalised infection and

requires treatment with ciprofloxacin

Chloramphe-nicol, amoxicillin or co-trimoxazole are less

effec-tive alternaeffec-tives The i.v route should be used at

N F E C T I O N O F T H E I N T E S T I N E S

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 patho-genic 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 prophyl-axis but, when it is indicated, a quinolone should be used

Verotoxic Escherichia coli (VTEC; O157) 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 1 1/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.

13

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

immuno-compromised 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

anti-microbial 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)

Proteus spp.

Klebsiella spp.

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 con-centrated 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 I/d) and

by frequent micturition

Drug treatment of urinary tract infection falls into several categories:

Lower urinary tract infection

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 patho-gens 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

Upper urinary tract infection

Acute pyelonephritis may be accompanied by septicaemia and it is advisable to start with genta-micin 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

Recurrent urinary tract infection

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,