[unlicensed indication], and vancomycin p. 534). When the
condition improves and the sensitivity of the Bacillus
anthracis strain is known, treatment may be switched to a
single antibacterial. Treatment should continue for 60 days
because germination may be delayed.
Cutaneous anthrax should be treated with either
ciprofloxacin [unlicensed indication] or doxycycline
[unlicensed indication] for 7 days. Treatment may be
switched to amoxicillin if the infecting strain is susceptible.
Treatment may need to be extended to 60 days if exposure is
due to aerosol. A combination of antibacterials for 14 days is
recommended for cutaneous anthrax with systemic features,
extensive oedema, or lesions of the head or neck.
prophylaxis should continue for 60 days. Antibacterial
prophylaxis may be switched to amoxicillin after 10–14 days
if the strain of B. anthracis is susceptible. Vaccination against
anthrax may allow the duration of antibacterial prophylaxis
Advice from a member of the Panel of Leprosy Opinion is
essential for the treatment of leprosy (Hansen’s disease).
Details can be obtained from the Hospital for Tropical
Diseases, London (telephone (020) 3456 7890).
The World Health Organization has made
recommendations to overcome the problem of dapsone
p. 577 resistance and to prevent the emergence of resistance
to other antileprotic drugs. Drugs recommended are
dapsone, rifampicin p. 582, and clofazimine below. Other
drugs with significant activity against Mycobacterium leprae
include ofloxacin p. 561, minocycline p. 566 and
clarithromycin p. 538, but none of these are as active as
rifampicin; at present they should be reserved as second-line
A three-drug regimen is recommended for multibacillary
leprosy (lepromatous, borderline-lepromatous, and
borderline leprosy) and a two-drug regimen for paucibacillary
leprosy (borderline-tuberculoid, tuberculoid, and
Multibacillary leprosy should be treated with a
combination of rifampicin, dapsone and clofazimine for at
least 2 years. Treatment should be continued unchanged
during both type I (reversal) or type II (erythema nodosum
leprosum) reactions. During reversal reactions neuritic pain
or weakness can herald the rapid onset of permanent nerve
damage. Treatment with prednisolone p. 678 should be
instituted at once. Mild type II reactions may respond to
aspirin. Severe type II reactions may require corticosteroids;
thalidomide p. 962 [unlicensed] is also useful in patients who
have become corticosteroid dependent, but it should be used
only under specialist supervision. Thalidomide is
teratogenic and, therefore, contra-indicated in pregnancy; it
must not be given to women of child-bearing potential
unless they comply with a pregnancy prevention
programme. Increased doses of clofazimine are also useful.
Paucibacillary leprosy should be treated with rifampicin
and dapsone for 6 months. If treatment is interrupted the
regimen should be recommenced where it was left off to
Neither the multibacillary nor the paucibacillary
antileprosy regimen is sufficient to treat tuberculosis.
Multibacillary leprosy in combination with rifampicin and
dapsone (3-drug regimen) (administered on expert
▶ Adult: 300 mg once a month, to be administered under
supervision and 50 mg daily, to be self-administered,
alternatively 300 mg once a month, to be administered
under supervision and 100 mg once daily on alternate
Lepromatous lepra reactions (administered on expert
▶ Adult: 300 mg daily for max. 3 months
Severe type II (erythema nodosum leprosum) reactions
(administered on expert advice)
▶ Adult: 100 mg 3 times a day for one month, subsequent
dose reductions are required, may take 4–6 weeks to
l CAUTIONS Avoid if persistent abdominal pain and
diarrhoea . may discolour soft contact lenses
l INTERACTIONS → Appendix 1: clofazimine
l SIDE-EFFECTS Abdominal pain . appetite decreased . dry
eye . eye discolouration . fatigue . gastrointestinal
discolouration of body fluids . skin discolouration
(including areas exposed to light). skin reactions . splenic
infarction . urine red . visual impairment. vomiting
(hospitalise if persistent). weight decreased
576 Bacterial infection BNF 78
l BREAST FEEDING May alter colour of milk; skin
l HEPATIC IMPAIRMENT Use with caution.
l RENAL IMPAIRMENT Use with caution.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: capsule
CAUTIONARY AND ADVISORY LABELS 8, 14, 21
▶ Lamprene (Imported (United States))
Clofazimine 50 mg Lamprene 50mg capsules | 100 capsule P s
Multibacillary leprosy in combination with rifampicin and
clofazimine (3-drug regimen)| Paucibacillary leprosy in
combination with rifampicin (2-drug regimen)
▶ Adult (body-weight up to 35 kg): 50 mg daily,
alternatively 1–2 mg/kg daily, may be selfadministered
▶ Adult (body-weight 35 kg and above): 100 mg daily, may
▶ Adult: (consult product literature or local protocols)
Treatment of mild to moderate Pneumocystis jirovecii
(Pneumocystis carinii) pneumonia (in combination with
Prophylaxis of Pneumocystis jirovecii (Pneumocystis
l UNLICENSED USE Not licensed for treatment of
pneumocystis (P. jirovecii) pneumonia.
deficiency . pulmonary disease . susceptibility to
l INTERACTIONS → Appendix 1: dapsone
neuropathy . photosensitivity reaction . psychosis . severe
cutaneous adverse reactions (SCARs). skin reactions . tachycardia . vomiting
SIDE-EFFECTS, FURTHER INFORMATION Side-effects are
dose-related. If dapsone syndrome occurs (rash with fever
and eosinophilia)—discontinue immediately (may progress
to exfoliative dermatitis, hepatitis, hypoalbuminaemia,
l PREGNANCY Folic acid p. 1025 (higher dose) should be
given to mother throughout pregnancy; neonatal
haemolysis and methaemoglobinaemia reported in third
l BREAST FEEDING Haemolytic anaemia; although
significant amount in milk, risk to infant very small unless
Blood disorders On long-term treatment, patients and their
carers should be told how to recognise signs of blood
disorders and advised to seek immediate medical attention
if symptoms such as fever, sore throat, rash, mouth ulcers,
purpura, bruising or bleeding develop.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: oral suspension, oral
CAUTIONARY AND ADVISORY LABELS 8
Dapsone 50 mg Dapsone 50mg tablets | 28 tablet P £36.22 DT =
Dapsone 100 mg Dapsone 100mg tablets | 28 tablet P £97.39
Lyme disease, also known as Lyme borreliosis, is an infection
caused by bacteria called Borrelia burgdorferi. It is
transmitted to humans by the bite of an infected tick. Ticks
are mainly found in grassy and wooded areas including
urban gardens and parks. Most tick bites do not cause Lyme
disease, and the prompt and correct removal of the tick
reduces the risk of infection.
Lyme disease usually presents with a characteristic
erythema migrans rash. This usually becomes visible
1–4 weeks after a tick bite, but can appear from 3 days to
3 months, and last for several weeks. It may be accompanied
by non-focal (non-organ related) symptoms, such as fever,
swollen glands, malaise, fatigue, neck pain or stiffness, joint
or muscle pain, headache, cognitive impairment, or
Other signs and symptoms of Lyme disease may also
appear months or years after the initial infection and are
typically characterised by focal symptoms (relating to at
least 1 organ system). These include neurological (affecting
cranial nerves, peripheral and central nervous systems), joint
(Lyme arthritis), cardiac (Lyme carditis), or skin
(acrodermatitis chronica atrophicans) manifestations.
g Patients diagnosed with Lyme disease should be given
treatment with an antibacterial drug; the choice of drug
should be based on presenting symptoms. In patients who
present with focal symptoms, a discussion with, or referral
to, a specialist should be considered but should not delay
In patients presenting with erythema migrans rash with or
without non-focal symptoms, oral doxycycline p. 564
[unlicensed indication] is recommended as first-line
treatment. If doxycycline cannot be given, oral amoxicillin
p. 548 should be used as an alternative. Oral azithromycin
p. 536 [unlicensed indication] should be given if both
doxycycline and amoxicillin p. 548 are unsuitable.
In patients presenting with focal symptoms of cranial nerve
or peripheral nervous system involvement, oral doxycycline
p. 564 [unlicensed indication] is recommended as first-line
treatment. If doxycycline cannot be given, oral amoxicillin
p. 548 should be used as an alternative.
In patients presenting with symptoms of central nervous
system involvement, intravenous ceftriaxone p. 528 is
recommended as first-line treatment. Oral doxycycline
[unlicensed indication] should be used as an alternative if
ceftriaxone p. 528 cannot be given, or when switching to oral
In patients with symptoms of Lyme arthritis or
acrodermatitis chronica atrophicans, oral doxycycline
[unlicensed indication] is recommended as first-line
treatment. If doxycycline cannot be given, oral amoxicillin
p. 548 should be used as an alternative. Intravenous
ceftriaxone p. 528 should be given if both doxycycline p. 564
and amoxicillin p. 548 are unsuitable.
In patients with symptoms of Lyme carditis who are
haemodynamically stable, oral doxycycline [unlicensed
indication] is recommended as first-line treatment. If
doxycycline cannot be given, intravenous ceftriaxone p. 528
should be used as an alternative.
In patients with symptoms of Lyme carditis who are
haemodynamically unstable, intravenous ceftriaxone p. 528 is
recommended. Oral doxycycline [unlicensed indication]
should be given when switching to oral antibacterial
g If symptoms continue to persist or worsen after
antibacterial treatment, patients should be assessed for
possible alternative causes, re-infection with Lyme disease,
treatment failure or non-adherence to previous antibacterial
treatment, or progression to organ damage caused by Lyme
disease (such as nerve palsy).
A second course of antibacterial treatment should be given
due to possible treatment failure, treatment with an
alternative antibacterial drug should be considered. A third
course of antibacterial treatment is not recommended, and
further management should be discussed with a national
reference laboratory or suitable specialist depending on
symptoms (for example, a rheumatologist or neurologist).
Lyme disease. National Institute for Health and Care
Excellence. NICE guideline 95. April 2018.
‘Be tick aware’–Toolkit for raising awareness of the
potential risk posed by ticks and tick-borne disease in
England. Public Health England. March 2018.
www.gov.uk/government/publications/tick-bite-risks-andprevention-of-lyme-disease
Infection from Staphylococcus aureus strains resistant to
meticillin [now discontinued] (meticillin-resistant Staph.
aureus, MRSA) and to flucloxacillin p. 554 can be difficult to
manage. Treatment is guided by the sensitivity of the
Rifampicin p. 582 or fusidic acid p. 571 should not be used
alone because resistance may develop rapidly. A
tetracycline alone or a combination of rifampicin and
fusidic acid can be used for skin and soft-tissue infections
caused by MRSA; clindamycin p. 535 alone is an alternative.
A glycopeptide (e.g. vancomycin p. 534) can be used for
severe skin and soft-tissue infections associated with MRSA;
if a glycopeptide is unsuitable, linezolid p. 572 can be used
available; linezolid must be given with other antibacterials if
the infection also involves Gram-negative organisms. A
combination of a glycopeptide and fusidic acid or a
glycopeptide and rifampicin can be considered for skin and
soft-tissue infections that have failed to respond to a single
Tigecycline p. 568 and daptomycin p. 569 are licensed for the
treatment of complicated skin and soft-tissue infections
A tetracycline or clindamycin can be used for
bronchiectasis caused by MRSA. A glycopeptide can be used
for pneumonia associated with MRSA; if a glycopeptide is
unsuitable, linezolid can be used on expert advice. Linezolid
must be given with other antibacterials if the infection also
involves Gram-negative organisms.
A tetracycline can be used for urinary-tract infections
caused by MRSA; trimethoprim p. 574 or nitrofurantoin
p. 590 are alternatives. A glycopeptide can be used for
urinary-tract infections that are severe or resistant to other
A glycopeptide can be used for septicaemia associated
See the management of endocarditis, osteomyelitis, or septic
arthritis associated with MRSA.
Prophylaxis with vancomycin or teicoplanin p. 532 (alone
or in combination with another antibacterial active against
other pathogens) is appropriate for patients undergoing
. there is a history of MRSA colonisation or infection
without documented eradication;
. there is a risk that the patient’s MRSA carriage has
. the patient comes from an area with a high prevalence of
See eradication of nasal carriage of MRSA in Nose p. 1201.
Active tuberculosis is treated in two phases—an initial phase
using four drugs and a continuation phase using two drugs in
fully sensitive cases. Treatment requires specialised
knowledge and supervision, particularly where the disease
involves resistant organisms or non-respiratory organs.
There are two regimens recommended for the treatment of
tuberculosis in the UK; variations occur in other countries.
Either the unsupervised regimen or the supervised regimen
should be used; the two regimens should not be used
concurrently. Compliance with therapy is a major
The concurrent use of four drugs during the initial phase is
designed to reduce the bacterial population as rapidly as
possible and to prevent the emergence of drug-resistant
bacteria. The drugs are best given as fixed-dose, combination
preparations unless one of the components cannot be given
because of resistance or intolerance. The treatment of choice
for the initial phase is the daily use of rifampicin p. 582,
ethambutol hydrochloride p. 586, pyrazinamide p. 588 and
isoniazid p. 587 (with pyridoxine hydrochloride p. 1080 for
prophylaxis of isoniazid-induced neuropathy); modified
according to drug susceptibility testing. Treatment should be
started without waiting for culture results if clinical features
or histology results are consistent with tuberculosis;
treatment should be continued even if initial culture results
are negative. The initial phase drugs should be continued for
two months. Where a positive culture for M. tuberculosis has
been obtained, but susceptibility results are not available
after two months, treatment with rifampicin, ethambutol
hydrochloride, isoniazid and pyrazinamide (with pyridoxine
hydrochloride) should be continued until full susceptibility
is confirmed, even if this is for longer than two months.
578 Bacterial infection BNF 78
Streptomycin p. 520 is rarely used in the UK but it may be
used in the initial phase of treatment if resistance to
isoniazid has been established before therapy is commenced,
or when patients cannot tolerate standard treatment.
After the initial phase, daily treatment is continued for a
further four months with rifampicin and isoniazid
(preferably given as a combination preparation) with
pyridoxine hydrochloride. Longer treatment is necessary for
meningitis, direct spinal cord involvement, and for resistant
organisms which may also require modification of the
The unsupervised treatment regimen should be used for
patients who are likely to take antituberculosis drugs reliably
without supervision. Patients who are unable or unlikely to
comply with daily administration of therapy should be
treated with the regimen described under Supervised
The standard unsupervised six month treatment regimen
may be used during pregnancy. Streptomycin should not be
The standard unsupervised six month treatment regimen
may be used during breast-feeding.
Drug administration should be fully supervised (directly
observed therapy, DOT) in patients who cannot comply
reliably with the treatment regimen. If daily directly
observed therapy is not possible, a supervised dosing
schedule of three times a week should be considered.
Regimens with a dosing schedule of fewer than three times a
Directly observed therapy should be offered to patients
. have a history of non-adherence;
. have previously been treated for tuberculosis;
. are in denial of the tuberculosis diagnosis;
. have multidrug-resistant tuberculosis;
. have a major psychiatric or cognitive disorder;
. have a history of homelessness, drug or alcohol misuse;
. are in prison, or have been in the past 5 years;
. are too ill to self-administer treatment;
. request directly observed therapy.
Multi-resistant Mycobacterium tuberculosis may be present in
immunocompromised patients. The organism should always
be cultured to confirm its type and drug sensitivity.
Confirmed M. tuberculosis infection sensitive to first-line
drugs should be treated with a standard six month regimen;
after completing treatment, patients should be closely
monitored. The regimen may need to be modified if infection
is caused by resistant organisms, and specialist advice is
Specialist advice should be sought about tuberculosis
in choosing the regimen and in avoiding potentially serious
interactions. Starting antiretroviral treatment in the first two
months of antituberculosis treatment increases the risk of
immune reconstitution syndrome. Treatment for
tuberculosis should not routinely exceed six months in
patients who are HIV-positive, unless the tuberculosis has
central nervous system involvement (in which case
treatment should not routinely extend beyond twelve
Infection may also be caused by other mycobacteria e.g. M.
avium complex, in which case specialist advice on
Central nervous system tuberculosis
Patients with active central nervous system tuberculosis
should be offered treatment with rifampicin, ethambutol
hydrochloride, isoniazid and pyrazinamide (with pyridoxine
hydrochloride for prophylaxis of isoniazid-induced
neuropathy) for two months. After completion of the initial
treatment phase, rifampicin and isoniazid (with pyridoxine
hydrochloride) should be continued for a further ten months.
Treatment for tuberculosis meningitis should be offered if
clinical signs and laboratory findings are consistent with the
diagnosis, even if a rapid diagnostic test is negative.
An initial high dose of dexamethasone p. 675 or
prednisolone p. 678 should be started at the same time as
antituberculosis therapy, and then slowly withdrawn over
Referral for surgery should be considered only in patients
who have raised intracranial pressure.
An initial high dose of oral prednisolone should be offered to
patients with active pericardial tuberculosis at the same time
as initiation of antituberculosis therapy; it should then be
slowly withdrawn over 2–3 weeks.
Clinicians should be aware that some patients with latent
tuberculosis are at increased risk of developing active
tuberculosis (such as patients who are HIV-positive, diabetic
or receiving treatment with a tumour necrosis factor alpha
inhibitor). These patients should be advised of the risks and
symptoms of active tuberculosis.
Note: the risk of adverse events to chemoprophylaxis in
patients aged over 35 years with a risk of hepatotoxicity is
likely to be greater than the potential benefit of treating
latent disease. When indicated, drug treatment should only
be offered to patients aged 35–65 years if hepatotoxicity is
not a concern. Treatment for latent tuberculosis is not
usually indicated in patients over 65 years.
Anyone aged under 65 years who is a close contact
(prolonged, frequent or intense contact, e.g. household
contacts or partners) of a person with pulmonary or
laryngeal tuberculosis should be tested for latent
tuberculosis. Chemoprophylaxis should be offered to all
patients aged younger than 65 years, with evidence of latent
tuberculosis if the close contact has suspected-infectious or
confirmed-active pulmonary or laryngeal drug-sensitive
Patients who are immunocompromised, such as those with
HIV or who have had a solid organ or allogeneic stem cell
transplant, should be tested for latent tuberculosis using an
appropriate method. Patients who test positive should then
be assessed for active disease, and if negative, offered
treatment for latent tuberculosis.
New NHS employees who are new entrants from a high
incidence country should be offered appropriate testing for
latent tuberculosis; those who are not new entrants from a
high incidence country, but who will be in contact with
patients or clinical materials should be offered appropriate
testing for latent tuberculosis if prior BCG vaccination
cannot be verified (see also BCG vaccine p. 1297).
Those who test positive should then be assessed for active
disease, and if negative, offered treatment for latent
Recommended dosage for standard unsupervised 6-month treatment
▶ body-weight up to 40 kg 3 tablets daily for 2 months (initial phase), use Rifater® Tablets,
preferably taken before breakfast;
▶ body-weight 40–49 kg 4 tablets daily for 2 months (initial phase), use Rifater® Tablets,
preferably taken before breakfast;
▶ body-weight 50–64 kg 5 tablets daily for 2 months (initial phase), use Rifater® Tablets,
preferably taken before breakfast;
▶ body-weight 65 kg and above 6 tablets daily for 2 months (initial phase), use Rifater®
Tablets, preferably taken before breakfast
Ethambutol hydrochloride Adult: 15 mg/kg once daily for 2 months (initial phase)
Rifampicin with isoniazid Adult:
▶ body-weight up to 50 kg 450/300 mg daily for 4 months (continuation phase after
2-month initial phase), use Rifinah®150/100 Tablets, preferably taken before breakfast;
▶ body-weight 50 kg and above 600/300 mg daily for 4 months (continuation phase after
2-month initial phase), use Rifinah®300/150 Tablets, preferably taken before breakfast
or (if combination preparations not appropriate):
Isoniazid Child: 10 mg/kg once daily (max. per dose 300 mg) for 6 months (initial and continuation
Adult: 300 mg daily for 6 months (initial and continuation phases)
▶ body-weight up to 50 kg 15 mg/kg once daily for 6 months (initial and continuation
phases); maximum 450 mg per day;
▶ body-weight 50 kg and above 15 mg/kg once daily for 6 months (initial and continuation
phases); maximum 600 mg per day
▶ body-weight up to 50 kg 450 mg once daily for 6 months (initial and continuation
▶ body-weight 50 kg and above 600 mg once daily for 6 months (initial and continuation
▶ body-weight up to 50 kg 35 mg/kg once daily for 2 months (initial phase); maximum
▶ body-weight 50 kg and above 35 mg/kg once daily for 2 months (initial phase);
▶ body-weight up to 50 kg 1.5 g once daily for 2 months (initial phase);
▶ body-weight 50 kg and above 2 g once daily for 2 months (initial phase)
Ethambutol hydrochloride Child: 20 mg/kg once daily for 2 months (initial phase)
Adult: 15 mg/kg once daily for 2 months (initial phase)
Recommended dosage for intermittent supervised 6-month treatment
Adult: 15 mg/kg 3 times a week (max. per dose 900 mg) for 6 months (initial and continuation phases)
Adult: 600–900 mg 3 times a week for 6 months (initial and continuation phases)
▶ body-weight up to 50 kg 50 mg/kg 3 times a week (max. per dose 2 g 3 times a week) for 2 months
▶ body-weight 50 kg and above 50 mg/kg 3 times a week (max. per dose 2.5 g 3 times a week) for
▶ body-weight up to 50 kg 2 g 3 times a week for 2 months (initial phase);
▶ body-weight 50 kg and above 2.5 g 3 times a week for 2 months (initial phase)
Ethambutol hydrochloride Child: 30 mg/kg 3 times a week for 2 months (initial phase)
Adult: 30 mg/kg 3 times a week for 2 months (initial phase)
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