FOSFOMYCIN
 CLINICAL APPLICATIONS
 COMPARATIVE EFFICACY
 TEICOPLANIN
 1. IN VIVO
 a. When compared in human sera after intravenous administration, fosfomycin
and teicoplanin exhibited similar bactericidal activity against staphylococci
(Vogt et al, 1995). Among the 40 staphylococcal strains cultured (20
staphylococcus aureus and 20 coagulase-negative staphylococci, one-half of
each group being oxacillin-resistant), activity of each drug was comparable.
Median serum inhibitory titres of fosfomycin were highest against oxacillinsusceptible S aureus. Both antibiotics killed over 99% of the microbes within 24
hours, although fosfomycin exerted its effect within 4 to 6 hours and was more
effective than was teicoplanin in bacterial growth reduction (Vogt et al, 1995).
Antibacterials
 CHOICE OF ANTIBACTERIAL
 STAPHYLOCOCCAL INFECTIONS
 Staphylococci are Gram-positive bacteria pathogenic to man. Species may be
differentiated by various methods including the coagulase test. Those species of
clinical importance are Staphylococcus aureus, which is usually coagulase-positive,
and Staph. epidermidis and Staph. saprophyticus, which are coagulase-negative.
 Staph. aureus colonises the skin and mucous membranes naturally and many people,
including neonates, may be staphylococcal carriers from time to time. Localised
Staph. aureus infections may follow surgery or trauma and commonly result in
abscess formation. Staphylococcal skin infections include impetigo and furunculosis.
Conditions associated with staphylococcal extracellular toxin production include
staphylococcal scalded skin syndrome, toxic shock syndrome, and staphylococcal
food poisoning. Staphylococcal septicaemia is usually a consequence of local
infection and may sometimes be associated with intravascular or intraperitoneal
catheters or with intravenous drug abuse. Septicaemia often results in staphylococcal
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endocarditis. Other possible complications of septicaemia are pneumonia and bone
and joint infections, although in these cases aspiration or local trauma, respectively,
may be the cause.
Staph. epidermidis is also a natural inhabitant of skin and mucous membranes and an
increasingly important nosocomial pathogen. Many infections are hospital-acquired
and are often associated with indwelling catheters. There has been an increased
incidence of bacteraemia due to Staph. epidermidis in neonatal units.
Staph. saprophyticus is a common cause of urinary-tract infections in young women.
Staphylococci were sensitive to benzylpenicillin when it was first introduced, but the
majority of strains are now resistant as a result of penicillinase production. Methicillin
and other penicillinase-resistant penicillins such as flucloxacillin were developed
because of their activity against these resistant staphylococci. However, methicillinresistant staphylococci soon emerged. Both coagulase-negative staphylococci and
Staph. aureus resistant to methicillin are generally resistant to all beta lactams and
often exhibit multiple resistance to other antibacterials (see Methicillin, Ref.). More
studies have been published on methicillin-resistant Staph. aureus (MRSA) than
methicillin-resistant coagulase-negative staphylococci, but both types are a serious
problem in hospitals around the world. Resistant strains may be endemic to a single
hospital or may be epidemic causing outbreaks of infection at more than one hospital.
Colonisation of hospital staff and patients with methicillin-resistant staphylococci is an
important factor in the spread of these infections. Current trends are towards health
care at home rather than in hospital and there are reports suggesting that MRSA is
becoming more prevalent in the community. (1-4)
Revised guidelines (5) for the control of MRSA in hospital were produced by a
combined working party of the British Society for Antimicrobial Chemotherapy, the
Hospital Infection Society, and the Infection Control Nurses Association in 1998. They
advise prompt isolation of infected or colonised patients, screening of patients and
staff in contact with such patients, the use of protective clothing and handwashing
with an antiseptic detergent or alcoholic rub; and the use by all patients of an
antiseptic detergent for washing and bathing. For eradication of nasal carriage they
recommend mupirocin nasal ointment or, if the strain is mupirocin-resistant,
chlorhexidine and neomycin cream. Eradication at other colonised sites is more
difficult: antiseptic detergents may be used for skin and hair washing; mupirocin in a
macrogol basis for small infected skin lesions, but not for burns or large raw areas;
hexachlorophane dusting powder for axillae and groins; and systemic rifampicin with
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fusidic acid or ciprofloxacin for throat or sputum colonisation if absolutely necessary.
(5) For the treatment of severe infections due to MRSA they recommend vancomycin
or teicoplanin, possibly combined with rifampicin, as the treatment of choice. (5)
Similarly recommendations have been made in a consensus review published in the
USA. (6)
Although ciprofloxacin may be used the emergence of widespread resistance in
methicillin-sensitive and methicillin-resistant Staph. aureus limits its usefulness (see
Ref.). Combination therapy may be helpful. Rifampicin is highly active against MRSA,
but it must always be used in combination with another drug to prevent the
emergence of resistance. Combinations of rifampicin with gentamicin, vancomycin,
co-trimoxazole, fusidic acid, quinolones, or novobiocin have been tried.
There has been concern over isolated reports from around the world of resistance or
reduced susceptibility to vancomycin, (7,8) and in response the Centers for Disease
Control in the USA produced interim guidelines. (9)
Staphylococcal vaccines have been used for the prophylaxis and treatment of
staphylococcal infections.
For the management of staphylococcal infections in general, see under the specific
disease headings.
For further information on the agents mentioned above, see
Chlorhexidine, Ref.
Ciprofloxacin, Ref.
Co-trimoxazole, Ref.
Fusidic Acid, Ref.
Hexachlorophane, Ref.
Mupirocin, Ref.
Neomycin, Ref.
Novobiocin, Ref.
Rifampicin, Ref.
Staphylococcal Vaccines, Ref.
Teicoplanin, Ref.
Vancomycin, Ref.
Rifampicin
See Also Antibacterials
 USES AND ADMINISTRATION
 Rifampicin belongs to the rifamycin group of antimycobacterials (Ref.) and is used in
the treatment of various infections due to mycobacteria and other susceptible
organisms (see Antimicrobial Action, Ref.). It is usually given combined with other
antibacterials to prevent the emergence of resistant organisms.
 Rifampicin is used, notably in combination with isoniazid and pyrazinamide, as a
component of multidrug regimens for the treatment of tuberculosis, and with dapsone
and clofazimine in the treatment of leprosy. It is a component of various regimens for
the treatment of opportunistic mycobacterial infections.
 Other uses include brucellosis, chancroid, chlamydial infections, the treatment of
staphylococcal endocarditis, penicillin-resistant pneumococcal meningitis,
prophylaxis of epiglottitis due to Haemophilus influenzae, Legionnaires' disease, the
prophylaxis of meningococcal and H. influenzae meningitis, mycetoma, the
eradication of pharyngeal streptococcal carriage in pharyngitis, Q fever, and in
various staphylococcal infections for treatment or prophylactically to reduce
staphylococcal carriage. For discussions of all these infections and their treatment,
see under Choice of Antibacterial, Ref..
 The usual adult dose of rifampicin is 600 mg daily by mouth, preferably on an empty
stomach, or by intravenous infusion as the base or the sodium salt; higher doses are
sometimes employed (see below).
 Rifampicin is used in the initial and continuation phases of short-course tuberculosis
regimens (Ref.) in combination with other antimycobacterials. Rifampicin is
administered orally on an empty stomach in single daily doses of 10 mg per kg bodyweight (maximum 600 mg) to children and adults or may be given intermittently two or
three times weekly in doses of 10 or 15 mg per kg (maximum 900 mg) to children and
adults. Alternatively doses may be expressed as follows: with daily administration,
adults weighing less than 50 kg receive 450 mg and those over 50 kg receive 600 mg;
with intermittent administration, adults receive 600 to 900 mg 2 or 3 times weekly. The
maximum recommended dose is considered to be 900 mg because a greater
incidence of adverse effects is associated with doses above 900 mg.
 In leprosy regimens (Ref.), rifampicin is usually given with dapsone for paucibacillary
leprosy, and with dapsone and clofazimine for multibacillary leprosy. Rifampicin is
given once monthly in a usual adult dose of 600 mg by mouth. Guidelines for monthly
doses in low-body-weight adults and in children are rifampicin 450 mg for adults
weighing less than 35 kg and children 10 to 14 years old. Low body-weight children
may be given 12 to 15 mg per kg monthly. Single-dose treatment with rifampicin,
ofloxacin, and minocycline may be an alternative in patients with single-lesion
paucibacillary leprosy.
 For prophylaxis against meningococcal meningitis and the treatment of
meningococcal carriers, rifampicin is usually given in a dose of 600 mg twice daily by
mouth for 2 days. Recommended doses for children in the UK are 10 mg per kg for
children between 1 and 12 years of age and 5 mg per kg for children under 12 months
each twice daily for 2 days; in the US children aged 1 month or more are given 10 mg
per kg and infants less then 1 month old are given 5 mg per kg, both twice daily for 2
days. For prophylaxis against meningitis due to Haemophilus influenzae a dose of 20
mg per kg is given once daily by mouth for 4 days with a maximum daily dose of 600
mg. This dose is suitable for adults and children over 3 months of age;
recommendations regarding use in infants vary and are discussed in detail below
(Ref.).
 In the treatment of brucellosis, Legionnaires' disease, and serious staphylococcal
infections a dose of 600 to 1200 mg daily in divided doses has been recommended in
combination with other drugs.
 Reduced doses are recommended for patients with impaired hepatic function and a
maximum of 8 mg per kg daily has been suggested.
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