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Internal Medicine Journal 2005; 35: S3-S16
Antibiotics currently used in the treatment of infections

caused by Staphylococcus aureus
C. RAYNER1* and W. J. MUNCKHOF 2
Facility for Anti-infective Drug Development and Innovation,Victorian College of Pharmacy, Monash University,
1
Parkville,Victoria and 2Infection Management Service, Princess Alexandra Hospital & District Health Service,
Brisbane, Queensland, Australia
Abstract typically multi-resistant (mrMRSA), and mrMRSA

Staphylococcal infections are a common and significant strains must always be treated with a combination of two
clinical problem in medical practice. Most strains of oral antimicrobials, typically rifampicin and fusidic acid,
Staphylococcus aureus are now resistant to penicillin, and because resistance develops rapidly if they are used as
methicillin-resistant strains of S. aureus (MRSA) are single agents. Most community-acquired strains of
common in hospitals and are emerging in the com- MRSA in Australia and New Zealand are non multi-
munity. Penicillinase-resistant penicillins (flucloxacillin, resistant (nmMRSA), and lincosamides (clindamycin,
dicloxacillin) remain the antibiotics of choice for the lincomycin) or cotrimoxazole are the antibiotics of
management of serious methicillin-susceptible S. aureus choice for less serious nmMRSA infections such as skin
(MSSA) infections, but first generation cephalosporins and soft tissue infections. New antibiotics such as
(cefazolin, cephalothin and cephalexin), clindamycin, linezolid and quinupristin / dalfopristin have good anti-
lincomycin and erythromycin have important therapeutic staphylococcal activity but are very expensive and should
roles in less serious MSSA infections such as skin and be reserved for patients who fail on or are intolerant of
soft tissue infections or in patients with penicillin hyper- conventional therapy or who have highly resistant strains
sensitivity, although cephalosporins are contra-indicated such as hVISA (heterogenous vancomycin-intermediate
in patients with immediate penicillin hypersensitivity S aureus). (Intern Med J 2005; 35: S3–S16)
(urticaria, angioedema, bronchospasm or anaphylaxis).
All serious MRSA infections should be treated with Key words: Staphylococcus aureus, antibiotics, drug
parenteral vancomycin or, if the patient is vancomycin selection, therapeutic drug monitoring, hospital-in-the-
allergic, teicoplanin. Nosocomial strains of MRSA are home.
INTRODUCTION This review discusses the efficacy and adverse effect

profiles of antibiotics that may be used to treat suspected
In Australia and New Zealand, antistaphylococcal peni- or confirmed infections caused by S. aureus, and provides a
cillins and glycopeptides are the antimicrobial agents background for subsequent reviews in this issue in which
most commonly selected to treat infections caused by more explicit indication-based recommendations for
methicillin-susceptible and methicillin-resistant Staphylo- managing staphylococcal infections are outlined. As well
coccus aureus, respectively. However, there are certain as systematically evaluating those antimicrobials used
clinical scenarios where these conventional therapies may primarily to treat infections caused by both methicillin-
not be optimal or feasible for patient care, and where susceptible and methicillin-resistant S. aureus, it also
other antibiotics may be more appropriate. The rationale examines the potential roles of more recently approved
for clinical use of certain antibiotics varies between indi- antibiotics, the controversies surrounding therapeutic drug
cations. Factors to consider when choosing an antibiotic monitoring of vancomycin and other antistaphylococcal
may include excellent efficacy, low incidence of toxicity, agents, and special considerations for ‘Hospital in the
low potential for resistance development, penetration of Home’ parenteral therapy of infections caused by S. aureus.
the antibiotic into certain tissues (e.g. bone, cerebrospinal
fluid), inexpensive cost, and stability and dosing con- DRUFUSED PRIMARILY TO TREAT
venience for home intravenous use.
METHICILLIN-SUSCEPTIBLE
STAPHYLOCOCCUS AUREUS (MSSA)
Correspondence to: Dr Wendy J. Munckhof, Infection Management INFECTIONS
Service, Princess Alexandra Hospital, and The University of
Queensland, Brisbane, Queensland, Australia. β-Lactam antibiotics
Email:Wendy_Munckhof@health.qld.gov.au Penicillins
*Current position: Clinical Pharmacologist, Roche Products Penicillins are the antimicrobial agents most commonly
Limited, 6 Falcon Way, Shire Park,Welwyn Garden City, UK. used to treat serious methicillin-susceptible staphylococcal
S4 Rayner & Munckhof
infections. β-Lactams exhibit time-dependent killing of particularly those requiring prolonged therapy, oral
S. aureus in vitro, with moderate postantibiotic effects.1 dicloxacillin may be preferable to oral flucloxacillin.
Maximal killing of S. aureus in animal models occurs The commonest toxicity of any of the penicillins is
when serum levels exceed the minimum inhibitory hypersensitivity, which occurs in between 1% and 10%
concentration (MIC) for 40% to 50% of the dosing of the population,12 and in these patients, an alternative
interval.2 High peaks are much less important than antimicrobial agent must be used. A careful history of
duration of exposure to drug, with maximal killing of S. the clinical manifestation of the penicillin allergy should
aureus occurring at concentrations only 3 to 4 times the be elicited. For a relatively mild and late manifestation
MIC.3 Hence, when considering pharmacodynamic such as rash, a cephalosporin antibiotic may be used,
principles, the goal of a dosing regimen for β-lactam although there is an increased risk of a reaction to these
antibiotics active against S. aureus would be to optimize drugs (see further below). In patients with a history of
the duration of exposure to the drug. For short half-life an immediate hypersensitivity reaction to penicillin
penicillins such as benzylpenicillin and flucloxacillin, this (urticaria, angioedema, bronchospasm, or anaphylaxis),
can best be done by continuous intravenous infusion, a other β-lactam agents are contraindicated,13 and a non-
therapeutic approach that can be utilized in ‘Hospital in β-lactam antibiotic should be chosen.
the Home’ programmes.
Several types of penicillins are used to treat staphylo- Penicillin/β-lactamase inhibitor combinations
coccal infections. As more than 80% of Australian strains The penicillins amoxicillin, ticarcillin and piperacillin are
of MSSA produce a penicillinase,4 a penicillinase- only active against the small percentage of strains of
resistant penicillin needs to be used in most patients. S. aureus that do not produce β-lactamase. However, the
However, for the minority of strains of S. aureus that do addition of a β-lactamase inhibitor such as clavulanate or
not produce penicillinase, benzylpenicillin remains an tazobactam will readily inhibit the β-lactamase of many
effective therapeutic agent. The most commonly used bacteria, including S. aureus and some Gram-negative
penicillinase-resistant penicillins in Australia are flu- and anaerobic bacteria.14,15 Hence, efficacy against
cloxacillin and dicloxacillin. Methicillin is no longer penicillin-resistant, methicillin-susceptible staphylococci
commercially available in Australia, due to the rela- will be restored with these combination agents, but the
tively high incidence of interstitial nephritis associated overall antibacterial spectrum is broader than with the
with its use, and nor are cloxacillin, oxacillin and penicillinase-resistant penicillins. For this reason,
nafcillin. penicillinase-resistant penicillins are recommended if
Flucloxacillin and dicloxacillin remain the most effec- MSSA is the sole pathogen. However, for mixed infec-
tive antibiotics for serious MSSA infections such as tions such as diabetic foot infections or infected bites
endocarditis or bone and joint infections. They have where Gram-negative organisms and anaerobes are often
better bactericidal activity than cephalosporins against present in addition to S. aureus, the combination prepa-
S. aureus in vitro and in the rabbit model of endocarditis.5 rations are often used.
However, first-generation cephalosporins are equally Penicillin/β-lactamase inhibitors currently available in
effective and potentially less toxic than flucloxacillin and Australia include amoxicillin/clavulanate (oral formula-
dicloxacillin for the treatment of minor staphylococcal tion), ticarcillin/clavulanate (parenteral) and piperacillin/
infections, such as skin and soft tissue infections. Both tazabactam (parenteral). As well as broadening the
flucloxacillin and dicloxacillin are available in oral and antibacterial spectrum, the addition of clavulanate
parenteral formulations, although due to precipitation to amoxicillin also increases the likelihood of adverse
problems and lack of evidence that it is stable in solution events such as diarrhoea and hepatitis.16,17 Ticarcillin/
over 24 h, parenteral dicloxacillin is not recommended clavulanate and piperacillin/tazabactam are more expen-
for use in continuous infusion regimens in ‘Hospital in sive than most other parenteral penicillins.
the Home’ programmes.
There are no significant differences in pharmacokinetic Cephalosporins
profiles or efficacy between flucloxacillin and di- First-generation (or moderate-spectrum) cephalosporins
cloxacillin,6,7 although there are some differences in their are stable to staphylococcal β-lactamase but are not as
toxicity profiles, leading to much recent debate about their bactericidal as penicillins against S. aureus in vitro or in
relative places in the therapy of staphylococcal infec- the rabbit model of endocarditis.5 Hence, penicillinase-
tions.8–10 Flucloxacillin is associated with a cholestatic resistant penicillins such as flucloxacillin or dicloxacillin
hepatitis in 1 per 15 000 treatment courses of the drug, are preferred to cephalosporins for serious staphylo-
and fatalities have been reported rarely. In case-control coccal infections such as endocarditis or bone and joint
studies, the main risk factors for flucloxacillin-associated infections, although first-generation cephalosporins are
cholestatic hepatitis were age over 55 years and duration useful alternatives in patients with penicillin hyper-
of therapy over 2 weeks.11 Cholestatic hepatitis has been sensitivity or intolerance. There is, however, a dearth of
reported less frequently for dicloxacillin than flucloxa- information from clinical trials that have directly
cillin, but dicloxacillin causes more infusion phlebitis and assessed the effectiveness of cephazolin or other first-
interstitial nephritis. If either dicloxacillin or flucloxacillin generation cephalosporins in endocarditis caused by
are to be used intravenously, consideration should be S. aureus.
given to prolonging the infusion time (to >1 h) or admin- Cephalosporins are also indicated in the treatment of
istration via a central line, if available. In older patients, less severe staphylococcal infections, such as skin and
Internal Medicine Journal 2005; 35: S3–S16

Antistaphylococcal anitbiotics S5
Table 1 Usual adult dosages of selected antistaphylococcal antibiotics†
Antibiotic Adult dosage/route of administration
Agents active against non-multiresistant MRSA strains (nmrMRSA)‡

Dicloxacillin 250–500 mg q6h (PO) or 0.5–2 g q6h (IV)
Flucloxacillin 250–1000 mg q6h (PO) or 0.5–2 g q6h (IV)
Amoxicillin/clavulanate 1 tablet (500 mg/125 mg or 875 mg/125 mg) PO bid
Ticarcillin/clavulanate 3.1 g IV q6-8h
Piperacillin/tazobactam 2 g/0.25 g–4 g/0.5 g IV q6h-8h
Cephazolin 0.5–2 g q8h IV
Cephalothin 0.5–1 g q6h IV
Cephalexin 250–1000 mg q6h PO
Clindamycin 150–450 mg q6h (PO) or 600–1200 mg/d in 3–4 equal doses (IV)
Co-trimoxazole (trimethoprim/sulphamethoxazole) 1 DS tablet (160 mg/800 mg) PO bid
Agents active against multiresistant MRSA strains (mrMRSA)§
Vancomycin 1000 mg q12h or 500 mg q6h (IV) [see section on therapeutic
drug monitoring]
Teicoplanin 12 mg/kg loading dose (2 doses in 12 h) followed by
3–6 mg/kg/day as a single daily maintenance dose (IV or IM)
[see section on therapeutic drug monitoring]
Rifampicin 300 mg q12h (IV or PO)
Fusidic acid 500 mg q8h-12h (PO or IV)
Ciprofloxacin 500 mg PO q12h or 400 mg IV q12h
Moxifloxacin 400 mg q24h (PO or IV)
Gatifloxacin 400 mg q24h (PO or IV)
Last-line agents
Linezolid 600 mg bid (IV or PO)
Quinupristin/dalfopristin 7.5 mg/kg q8h-q12h (IV) [Note: IV dosing; requires central venous
catheter due to occurrence of phlebitis]
†Range of doses listed may change depending on the nature of the specific infection, organ dysfunction, and other factors. Consult approved
product information for further details.

‡nmrMRSA = resistant to 0, 1 or 2 non-β-lactam agents.
§mrMRSA = resistant to 3 or more non-β-lactam agents.
IV, intravenous; MRSA, methicillin-resistant S. aureus; PO, oral.
soft tissue infections, because there is potentially less efficacy in a twice-daily parenteral dose for the treat-
toxicity than penicillinase-resistant penicillins and ment of skin and soft tissue infections, and dosing may
dosing is more convenient (Table 1).The major toxicities be decreased to once-daily with the addition of
of the cephalosporins are hypersensitivity and rash, but probenecid to increase its half-life.23 This strategy makes
they are much less likely to cause serious adverse events it convenient for ‘Hospital in the Home’ use. Later
such as hepatitis, interstitial nephritis or phlebitis than generation cephalosporins (i.e. second-generation agents
the penicillinase-resistant penicillins.6 As between 3% with moderate antibacterial spectra and enhanced anti-
and 8% of patients who are hypersensitive to penicillins Haemophilus or and antianaerobic activity, and third- or
will exhibit cross-reactivity with cephalosporins, fourth-generation agents with broad antibacterial spectra
predominantly as a rash,12,18,19 if there is a history of an with or without anti-Pseudomonas activity) all have
immediate hypersensitivity reaction to penicillins broader antibacterial spectra than the first-generation
(urticaria, angioedema, bronchospasm or anaphylaxis), cephalosporins, with either the same (some second-
cephalosporins are contraindicated. generation, all fourth-generation agents) or less (some
Cephazolin is more susceptible than cephalothin to second-generation, all third-generation agents) anti-
hydrolysis by β-lactamases produced by some strains of staphylococcal activity, along with increased costs.6
S. aureus.20 Clinical failure of cephazolin in endocarditis Hence, first-generation cephalosporins are preferred in
due to S. aureus has been reported several times.21 One the specific treatment of staphylococcal infections,
group suggested only using cephazolin if high inoculum unless the infection is caused by mixed organisms, in
MIC testing or molecular characterization of the which case a broader spectrum, later-generation agent
isolate’s β-lactamase showed it was susceptible to may be required.
cephazolin.22
First-generation agents currently available in Carbapenems
Australia include cephalexin (oral formulation), cepha- Carbapenems such as imipenem and meropenem are
zolin (IV) and cephalothin (IV). Cephazolin has good extremely broad-spectrum, expensive, parenteral β-lactam

agents with good activity against many bacterial species, and protein synthesis by binding to the 50s ribosomal
including MSSA.14,24 Carbapenems are occasionally unit. It has activity against S. pneumoniae, S. pyogenes and
used to treat MSSA in mixed infections but, in general, MSSA, as well as a broad range of Gram-positive and
should be regarded as agents to be held in reserve for the Gram-negative anaerobes.40 It is not active against
treatment of staphylococcal infections. multiresistant MRSA (mrMRSA), but MSSA and most
strains of non-multiresistant MRSA (nmrMRSA) are
Non-β-lactam antibiotics generally clindamycin susceptible.30–32 Clindamycin is
essentially bacteriostatic, displays time-dependent
Macrolides and azalides activity at concentrations >4 times the MIC,41 and has a
Macrolides such as erythromycin, clarithromycin and modest in vitro postantibiotic effect against S. aureus.42
roxithromycin, and the azalide agent azithromycin act by Like the macrolides, it is bacteriostatic and therefore
binding to the 50s ribosome and inhibiting bacterial should be avoided as the sole treatment for endocarditis.
protein synthesis.25 In general, they are inactive against Clindamycin is available in both intravenous and oral
multiresistant methicillin-resistant S. aureus (mrMRSA),26 formulations. It has an oral bioavailability of 90%,
but are active against approximately 85% of MSSA27 is extensively bound to plasma proteins (>90%),
and 65% to 75% of non-multiresistant MRSA distributed widely in most tissues and body fluids
(nmrMRSA).28–32 Against extracellular pathogens, (except for cerebrospinal fluid), and has a short plasma
including S. aureus, macrolides and azalides are generally half-life of approximately 2 h.40,43,44 It is extensively
considered bacteriostatic, time-dependent bacterial metabolized by the liver to active metabolites.40 Clinda-
killers, and they require concentrations to be at least 4 to mycin demonstrates good penetration into bone and
5 times the MIC, and to exceed the MIC for at least 50% abscesses,45 and hence is an effective therapy for MSSA
of the dosing interval, for an optimal outcome based on osteomyelitis and septic arthritis.46–48
general findings for time-dependent killing drugs from Clindamycin is now often used as a first-line agent to
in vivo infection models.33–35 treat skin and soft tissue infections caused by
In general, however, bacteriostatic agents should be nmrMRSA.22,31,36,49,50 Because of the relatively recent emer-
avoided in the treatment of serious infections such as gence of nmrMRSA, most publications are either small
endocarditis. Also, erythromycin is not recommended as case series of nmrMRSA infections31 or extrapolations
empirical therapy for staphylococcal skin and soft tissue from the treatment of MSSA with clindamycin;51 good
infections, as up to 15% of strains are erythromycin- clinical trials of the therapy of nmrMRSA have yet to be
resistant and there is a relatively high incidence of nausea conducted. Also, some erythromycin-resistant strains of
and vomiting (oral formulation) or phlebitis (IV formu- nmrMRSA may have inducible MLSB resistance to clin-
lation) with this drug.36 However, if alternative agents damycin,52 which can be tested for in the laboratory with
such as β-lactams or clindamycin are contraindicated, the erythromycin-clindamycin disc approximation test.
erythromycin is an appropriate therapeutic choice for If this is not possible, erythromycin-resistant strains
erythromycin-susceptible strains. should be reported as clindamycin resistant.
The macrolides and azalides are extensively
distributed into tissues – particularly azithromycin and Co-trimoxazole (trimethoprim/sulphamethoxazole)
roxithromycin which have long half-lives compared Co-trimoxazole is a combination of two antimicrobials,
with erythromycin (68 h and 8–15 h vs 2–4 h, respec- trimethoprim and sulphamethoxazole, which inhibit
tively).37,38 Resistance to erythromycin usually confers bacterial folate synthesis at two different enzymatic
resistance to the newer macrolides and azalides, as well stages. Most strains of MSSA and nmrMRSA in Australia
as reduced activity compared with other drug classes and New Zealand are currently susceptible to cotrimoxa-
including the lincosamides and streptogramins.39 zole,28–31 while most Australian strains of multiresistant
Prior to prescribing a macrolide, it is particularly MRSA (mrMRSA) are resistant.27,53 Co-trimoxazole is
important to consult the drug interaction profiles in rarely used to treat serious staphylococcal infections such
the prescribing information. This is especially important as endocarditis, as it is inferior to the β-lactams and
for erythromycin and clarithromycin, but less so for glycopeptides. In a study of the treatment of experimental
roxithromycin and azithromycin. Unlike the latter drugs, S. aureus endocarditis in rabbits, cotrimoxazole proved
erythromycin and clarithromycin are potent inhibitors of inferior to cloxacillin, vancomycin and teicoplanin,54 and
the cytochrome P450 isoenzymes (particularly 3A4 and in intravenous drug users with MSSA endocarditis, it was
1A2), which may lead to serious drug interactions with a inferior to vancomycin.55 A recent review of case reports,
large number of other drugs including warfarin, theo- case series and clinical studies that focused on the use of
phylline, ergot alkaloids, carbamazepine and cisapride. cotrimoxazole for treatment of severe S. aureus infections
suggested that it may have a limited role in treating severe
Lincosamides infections, but randomised comparator-controlled
The lincosamides, lincomycin and clindamycin are studies are required to establish its place in therapy.56
chemically unrelated to the macrolides, although there Hence, cotrimoxazole is mostly used orally in the treat-
are some structural similarities. Clindamycin is a ment of minor staphylococcal infections caused by
synthetic derivative of lincomycin, but has a broader MSSA, for which it is an effective therapy.57
spectrum of antibacterial activity and improved oral More recently, with the advent of nmrMRSA, cotri-
absorption. Clindamycin inhibits peptide chain initiation moxazole has experienced a therapeutic resurgence. In
Australia and New Zealand, most nmrMRSA strains are endocarditis, the doses of gentamicin used were 1 mg/kg
currently susceptible to cotrimoxazole,28–31 and either IV three times daily.64
clindamycin or cotrimoxazole are the agents most
commonly used to treat skin and soft tissue infections DRUGS USED PRIMARILY TO TREAT
caused by nmrMRSA,36 although published experience METHICILLIN-RESISTANT
is limited.58 STAPHYLOCOCCUS AUREUS (MRSA)
The most common adverse events of cotrimoxazole INFECTIONS
are nausea, diarrhoea and rash. Stevens–Johnson
syndrome, neutropenia, thrombocytopenia and nephro- Vancomycin
toxicity may also occur but are rare.6 Age is a risk factor Vancomycin is a Gram-positive, cell-wall active
for developing serious adverse reactions, and special care glycopeptide antibiotic that demonstrates antibacterial
must be exercised when prescribing cotrimoxazole to behaviour largely independent of its concentration. In
elderly patients. vitro, maximal antibacterial effects occur with concentra-
tions 4–5 times the MIC. Vancomycin also displays
Tetracyclines persistent effects which minimize the occurrence of
The tetracyclines are currently not widely used for the bacterial regrowth at times when the concentration of
treatment of staphylococcal infections. Most strains of antibiotic has declined to a level less than the MIC.67–69
mrMRSA, and many strains of nmrMRSA and MSSA Vancomycin is extensively used to treat staphylococcal
are resistant to this group of drugs.27 However, some infections, especially those caused by MRSA. In vitro,
strains of mrMRSA that are tetracycline-resistant are animal model, and human clinical studies (including
minocycline-susceptible, and minocycline is sometimes endocarditis)70 have demonstrated that vancomycin
used in the treatment of MRSA infections in developing evokes slower and incomplete bactericidal effects in
countries where vancomycin is not available, although MSSA compared with β-lactams.71–74 Hence, when
clinical data are relatively limited.59,60 sensitivity allows, antistaphylococcal penicillins are
The major toxicities of the tetracyclines are gastroin- preferred to glycopeptides against S. aureus. Also, in the
testinal upset, candidal superinfection, photosensitivity, last few years, vancomycin-intermediate Staphylococcus
and, in children, discoloration of teeth. aureus (VISA), heterogenous VISA (hVISA), and
vancomycin-resistant Staphylococcus aureus (VRSA) have
Aminoglycosides evolved.75,76 A clinical pointer to their possible presence
Most strains of MSSA and nmrMRSA are susceptible to may be failure of vancomycin therapy for MRSA infec-
gentamicin, but most strains of mrMRSA are gentamicin- tion despite therapeutic vancomycin levels. VISA and
resistant.61,62 Hence, many microbiology laboratories hVISA can be difficult to detect with routine suscept-
currently use gentamicin susceptibility as a rough guide ibility testing, and the microbiology laboratory should
to likely community acquisition of MRSA. The main be alerted so that additional methodology is used
exception is a British hospital-acquired strain of (see review on S. aureus with reduced susceptibility to
nmrMRSA, UK EMRSA-15, which is gentamicin- vancomycin in this issue).
susceptible and has caused outbreaks in Australian Vancomycin is a high molecular weight compound that
hospitals.63 is not absorbed orally and has to be administered by intra-
As the antibacterial activity of gentamicin is primarily venous infusion. In comparison with other antibiotics
against Gram-negative bacteria, its role in the treatment such as the β-lactams, vancomycin has a long plasma half-
of staphylococcal infections is limited. It is primarily life of approximately 6 h in patients with normal renal
used for synergy in the treatment of staphylococcal function.77 This is considerably extended in patients with
endocarditis. In a study in which gentamicin was added renal dysfunction (half-life is up to 7.5 days in anephric
to nafcillin in the treatment of staphylococcal endo- patients, indicating minimal non-renal clearance), and
carditis, there was a more rapid clinical defervescence dosage adjustment is therefore required in these patients.77
and sterilization of blood cultures during the first week, Vancomycin is generally considered to have a high degree
but the ultimate outcome was unaffected. Hence, the of tissue penetration,77–79 although some investigators
authors recommended that gentamicin be added in contend that suboptimal tissue concentrations may
the first 5–7 days only.64 Gentamicin is also some- contribute to poor outcomes in patients with MRSA
times used in the treatment of prosthetic valve pneumonia80 and other deep-seated MRSA infections.
endocarditis, although this is mostly for infection caused Penetration of the drug into cerebrospinal fluid (CSF) is
by methicillin-resistant, gentamicin-susceptible strains of variable and dependent on whether or not meningitis
Staphylococcus epidermidis65 (see also review on endo- is also present.81 One study demonstrated average
carditis in this issue). CSF/serum concentration ratios of 0.18 in patients
Gentamicin must be given parenterally, and it without meningitis and 0.48 in patients with meningitis.82
commonly causes nephrotoxicity and ototoxicity. As it Vancomycin can cause an infusion rate-dependent
has a narrow therapeutic window, gentamicin concentra- and histamine-mediated flushing of the skin, sometimes
tions and renal function need to be monitored carefully. accompanied by angioedema, known as ‘red man’
Once-daily dosing is now used for most therapeutic indi- syndrome.83,84 It has also been linked to ototoxicity and
cations, but this has not been studied in staphylococcal nephrotoxicity, although it is now thought to be much
endocarditis.66 In studies in patients with staphylococcal less frequently associated with these adverse effects than
initially believed.83 The majority of reports relating to Rifampicin is administered intravenously or orally,
vancomycin-associated ototoxicity and nephrotoxicity and it extensively penetrates into tissues (including
originated from data obtained nearly four decades pyogenic bone and pulmonary lesions), body fluids and
ago.83,85 Much of the data implicating vancomycin with abscesses.97 As approximately 30% of a dose of
toxicity is plagued by concomitant administration of rifampicin is excreted unchanged in the urine, doses
other ototoxic or nephrotoxic drugs, associated disease, should be reduced in the presence of hepatic dysfunc-
poor documentation of the timing of serum concentration.92 Patients taking rifampicin should be warned
tion measurements, varied definitions of toxicity, and the about reddish-orange staining of urine and contact
absence of appropriate audiometric or renal function lenses, and about the potential for drug interactions, as
data.85 The role of therapeutic drug monitoring for rifampicin may cause numerous interactions including
vancomycin toxicity has also been questioned widely in enhanced metabolism of the oral contraceptive pill and
the literature.85 Dosing considerations and therapeutic decreased concentrations (and effects) of cytochrome
drug monitoring of vancomycin are discussed below. P450 3A4 (CYP3A4) substrates such as cyclosporin,
nifedipine and prednisolone.92 Rifampicin may cause
Teicoplanin gastrointestinal upsets in up to 17% of patients, while
Like vancomycin, teicoplanin is a glycopeptide that less than 5% may develop a mild maculopapular rash
inhibits bacterial growth by inhibiting cell wall biosynthesis with long-term therapy or elevations in liver function
and, in general, it has similar activity against Gram- tests.98 Rarely, rifampicin has caused immune-mediated
positive aerobic and anaerobic cocci (including MRSA influenza symptoms, haematological abnormalities and
and C. difficile, respectively).86,87 Teicoplanin also exhibits interstitial nephritis.98
time-dependent bacterial killing and possesses a signifi- The major therapeutic indication for rifampicin in
cant postantibiotic effect in vitro.86 In vivo, it appears to staphylococcal infections is in oral combination therapy
be at least as effective as vancomycin,88,89 although the of mrMRSA infections. In Australia, it is usually
number of clinical trials comparing it with vancomycin is combined with fusidic acid or, if the isolate is suscep-
limited. Hence, it cannot be stated with certainty that the tible, ciprofloxacin. However, rifampicin is a relatively
two drugs are equally therapeutically effective. In one difficult and expensive drug for patients to obtain
non-comparative retrospective study in patients treated outside the public hospital system in Australia, as it is
with teicoplanin (mostly in combination with rifampicin currently not approved under the Pharmaceutical
and/or gentamicin) for endocarditis, cure without Benefits Scheme for the treatment of staphylococcal
surgery was achieved in 48% of cases.90 infections. Hence, for the treatment of MSSA and
Unlike vancomycin, ‘red man’ syndrome is extremely nmrMRSA infections, there are usually cheaper, less
rare with teicoplanin, and it can be administered as toxic and more readily available therapeutic alternatives.
either an intramuscular or intravenous injection.83 Sometimes rifampicin has been considered for
Teicoplanin also has a lesser propensity to cause nephro- addition to a standard regimen in the treatment of
toxicity than vancomycin.83 It is 90% bound to plasma serious staphylococcal infection. An unpublished multi-
albumin, and as a consequence of its prolonged terminal centre Australian study of 97 patients given either
half life of 155–168 h, is administered once daily.86,87 rifampicin/flucloxacillin or flucloxacillin for methicillin-
Since its pharmacokinetics are variable and affected by a susceptible S. aureus found no difference in outcome,
number of patient factors (e.g. renal function, burns, with a tendency for patients given rifampicin to have
intravenous drug abuse), therapeutic drug monitoring of prolonged fever duration (J. Turnidge, personal commu-
teicoplanin is useful to ensure efficacy (see further below). nication). Of more concern is the anecdotal evidence
that adding rifampicin to vancomycin selects for
Rifampicin rifampicin resistant S. aureus,99 despite US recommen-
Rifampicin is a complex macrocyclic antibiotic that specif- dations to use this combination.100 The addition of
ically inhibits chain initiation of bacterial DNA-dependent rifampicin to failing regimens remains controversial at
RNA polymerase by binding to the B-subunit of the this time.
enzyme.91,92 It is bactericidal and has a concentration-
dependent, prolonged postantibiotic effect. Rifampicin is Fusidic acid
active against many pathogens including S. aureus, Fusidic acid arrests bacterial protein synthesis by inter-
coagulase-negative staphylococci, and mycobacteria. In fering with an elongation factor that promotes
Australia, about 90% of hospital strains of mrMRSA are translocation on the bacterial ribosome.101,102 At higher
rifampicin-susceptible.4 Unfortunately, resistance occurs concentrations it is bactericidal, but otherwise is bacte-
rapidly via 1-step target-site mutations in the B-subunit of riostatic.103 There are no studies, to our knowledge, of
RNA polymerase. Therefore, rifampicin must always be pharmacodynamic predictors of efficacy of fusidic acid,
administered in combination with another antibiotic,93,94 and the drug has a relatively short postantibiotic
especially when the minimum bactericidal concentration effect.103,104 Unlike other agents with Gram-positive
of the original antibiotic is high, and in patients with antibacterial activity, fusidic acid has only modest
deep-seated infections such as osteomyelitis or refractory activity against streptococci, but retains activity against
endocarditis.92 The development of rifampicin resistance MSSA and MRSA.105 Currently, about 95% of strains of
in MRSA is rare if the drug is combined with fusidic acid95 mrMRSA are fusidic acid-susceptible, but there has
or therapeutic concentrations of linezolid.96 been a relatively recent increase in resistance, possibly
due to selection by the community use of a topical The newer fluoroquinolones gatifloxacin and moxi-
preparation of fusidic acid.4 floxacin are more potent antistaphylococcal agents than
Like rifampicin, fusidic acid is available for intra- ciprofloxacin, and are 5- to 10-fold more active against
venous or oral administration, and it extensively S. aureus.108 However, they do not have useful activity
penetrates into tissues.106 However, it is more highly against ciprofloxacin-resistant strains.116 The majority of
bound to plasma proteins (95% to 97%) and has a mrMRSA strains are resistant117 and hence, in Australia,
longer plasma half life (14 h vs 4–5 h for rifampicin).106 these agents are usually not indicated for the treatment
Gastrointestinal upset may be dose-limiting, and hyper- of mrMRSA infections. If strains are susceptible, care
bilirubinaemia may occur in up to 50% of patients.107 should be taken when they are used to treat serious
Use of fusidic acid is generally restricted to the con- staphylococcal infections such as osteomyelitis or septic
tinuing oral and outpatient treatment of mrMRSA arthritis. As with all fluoroquinolones, gatifloxacin and
infections in combination with rifampicin or, if the moxifloxacin are best combined with another active
isolate is susceptible, ciprofloxacin.107 Like rifampicin, agent in the treatment of mrMRSA infections due to
there are usually cheaper, less toxic and more readily potential resistance development. In vitro studies have
available therapeutic alternatives for the treatment of shown that resistant mutants of S. aureus occur readily
MSSA and nmrMRSA infections. after serial passage on media containing either gati-
floxacin or moxifloxacin,118,119 although more serial
Fluoroquinolones passages were required for S. aureus to acquire resistance
Broad-spectrum fluoroquinolones such as ciprofloxacin, with moxifloxacin than the older fluoroquinolones
gatifloxacin and moxifloxacin are active against S. aureus, ofloxacin or levofloxacin.120 It has been postulated that
and exhibit concentration-dependent killing and a the newer fluoroquinolones do not select for resistance
moderate postantibiotic effect in vitro and in vivo.3,108 as rapidly as the older compounds due to their dual
Studies in animals models and humans have shown that activity against DNA gyrase and topoisomerase IV.121,122
the principal predictor of bacterial killing by fluoro- Moxifloxacin and gatifloxacin both have excellent
quinolones is the 24-h AUC (area under the plasma bioavailability and rarely need to be given parenterally.
concentration-time curve)/MIC ratio (AUC24/MIC Unlike ciprofloxacin, cytochrome P450 is not involved in
ratio). A peak concentration/MIC ratio of >10 is also the metabolism of either moxifloxacin or gatifloxacin,
important in the prevention of selection of resistant and there is no interaction with theophylline. However,
mutants during treatment.109–111 gatifloxacin may interact with digoxin, probenecid and
Fluoroquinolones are not first-line agents in the treat- oral antidiabetic agents, and moxifloxacin may rarely
ment of staphylococcal infections for several reasons. interact with warfarin, so care should be taken if these
Ciprofloxacin, which is the fluoroquinolone most drugs are used concomitantly.123 As with all fluoro-
commonly used to treat staphylococcal infections in quinolones, absorption may be decreased if drugs
Australia, is a relatively expensive antimicrobial agent, containing multivalent cations (antacids, sucralfate,
and its extensive use has been associated with relatively calcium, zinc, magnesium and iron) are given at the
rapid emergence of resistance in Gram-positive same time. Also, patients on drugs that prolong the
bacteria.61,112,113 Whereas 95% of mrMRSA strains were cardiac QTc interval (e.g. quinidine, procainamide,
susceptible to ciprofloxacin in 1989, only 25% are now amiodarone and sotalol) should not receive either gati-
susceptible, although most strains of MSSA remain floxacin or moxifloxacin, as the QTc interval may be
ciprofloxacin susceptible. Ciprofloxacin is much more further lengthened, resulting in ventricular arrhythmias,
active against Gram-negative bacteria than against including Torsades de pointes.124,125
staphylococci, and staphylococcal MICs are usually close The adverse effects of both moxifloxacin and gati-
to the susceptibility breakpoint.114 Also, staphylococci floxacin are mostly mild and the most common are
may develop ciprofloxacin resistance during treatment, nausea, diarrhoea and dizziness. Rare adverse events
especially when used to treat mrMRSA and when include tendonitis, hepatotoxicity126–128 and, with gati-
monotherapy is used.61 As with rifampicin and fusidic floxacin, hypoglycaemia129 which may be related to age
acid, ciprofloxacin should never be used alone to treat and AUC.130
mrMRSA infections, but it is occasionally used in combi-
nation with rifampicin or fusidic acid to treat the minority NEW DRUGS USED PRIMARILY TO
of mrMRSA infections that are ciprofloxacin-susceptible. TREAT STAPHYLOCOCCUS AUREUS
Ciprofloxacin is well absorbed orally and rarely needs INFECTIONS WHERE
to be given parenterally. Adverse events are relatively CONVENTIONAL THERAPY IS
uncommon but include gastrointestinal effects, INAPPROPRIATE
headaches and dizziness, and rash. Ciprofloxacin does
inhibit cytochrome P450 1A2, and can result in Streptogramins
increased serum concentrations of drugs such as theo-
phyllline, caffeine, clopidogrel, fluvoxamine, propranolol Quinupristin/dalfopristin
and warfarin. Also, like all fluoroquinolones, it binds to Quinupristin/dalfopristin is a new parenteral anti-
drugs containing multivalent cations (antacids, sucral- microbial preparation comprised of two streptogramins.
fate, calcium, zinc, magnesium and iron), resulting in a Each drug binds to a different site on the bacterial ribo-
marked decrease in oral absorption of the drug.115 somal subunit and acts synergistically in disrupting both
early and late phases of bacterial protein synthesis.25 was one-tenth that of linezolid. Subsequent to publi-
Quinupristin/dalfopristin exerts a time-dependent, cation of the above, pristinamycin use at the study
bacteriostatic (or slow bactericidal) activity and a hospital increased substantially, being used in situations
prolonged in vitro postantibiotic effect (4.6–7 h) against where rifampicin/fusidate is problematic (resistance,
S. aureus.35 Based on in vivo models, concentrations intolerance, or interactions, e.g. rifampcin with warfarin)
should exceed the MIC for ~50% of the dosing interval as a cheaper and better tolerated alternative to oral line-
for bactericidal activity, and the AUC of quinupristin/ zolid (I. Gosbell, personal communication).
dalfopristin divided by the MIC of quinupristin has been
found to be associated with efficacy.35,131 The postanti- Oxazolidinones
biotic effect may be reduced significantly if the MRSA Linezolid is a synthetic antimicrobial and the first of the
strain is constitutively resistant to erythromycin.132 oxazolidinone class. Virtually all Gram-positive bacteria
In preregistration clinical studies, quinupristin/ are susceptible (including MRSA), regardless of their
dalfopristin has been shown to have similar success rates susceptibility to other agents.135,139 Linezolid acts on
to comparators in complicated skin and skin structure bacteria via the inhibition of a novel site in ribosomal
infections, catheter-related bacteraemia caused by protein synthesis, interfering with functional initiation
staphylococci (including MRSA), and hospital-acquired complex formation. Linezolid is available for both IV
pneumonia caused by staphylococci and Streptococcus and oral administration, has essentially 100% oral
pneumoniae.133–135 As quinupristin/dalfopristin inhibits bioavailability, and penetrates well into extravascular
CYP 3A4 and the metabolism of compounds such as sites including bone.140–142 In vitro pharmacodynamic
cyclosporin and midazolam, it increases plasma concen- studies have demonstrated that it has bacteriostatic
trations of these CYP3A4 substrates.135 Peripheral activity against enterococci, minimal bactericidal activity
infusion site reactions occur in about 75% of patients, against staphylococci, and is highly bactericidal against
requiring IV administration via central venous access. streptococci. Clinical and bacteriologic outcomes in
Arthralgia and myalgia may also occur in 13% to 50% patients are optimized by maintaining concentrations
of patient courses.135 above the MIC at all times and an AUC/MIC ratio of
Quinupristin/dalfopristin is indicated for the treatment 80–120 for bacteraemia, lower respiratory tract infec-
of suspected or proven MRSA or vancomycin-resistant tions, and skin and soft tissue infections.143
E. faecium infections requiring intravenous therapy where Linezolid has been shown to have equal or superior
other antibiotics are inappropriate. It is, however, very success rates to comparators in treating infections
expensive in comparison with older agents. caused by Gram-positive organisms, including MRSA,
in studies of community-acquired pneumonia, noso-
Pristinamycin comial pneumonia, and skin and soft tissue
Pristinamycin is an older oral streptogramin antibiotic infections.144–146 In non-comparative compassionate use
that is currently licensed in some European countries, programmes, linezolid at a dose of 600 mg twice daily
including France and Spain, but is not commercially has been shown to achieve clinical cure rates of 91.5% in
available in Australia. Its therapeutic role is therefore evaluable patients when treating vancomycin-resistant
likely to be small, but it has been used as an oral alter- enterococci (E. faecium and E. faecalis), MRSA, and
native in patients with mrMRSA infections where other infections in adults.147 Linezolid may also be
rifampicin, fusidic acid or ciprofloxacin are contraindi- effective in treating deep-seated infections such as
cated by resistance or allergy. It is substantially cheaper osteomyelitis.148
than either quinupristin/dalfopristin or linezolid. In an Resistance to linezolid has been reported in entero-
open-label study of the treatment of mrMRSA chest or cocci and rarely in MRSA.149,150 Reversible suppression
skin and soft tissue infections, pristinamycin proved an of indices of haematologic function, including anaemia,
effective therapy.136 In this study, it was combined with thrombocytopenia and leukopenia, may occur in some
oral doxycycline (if the isolate was doxycycline- patients and may be related to patient factors, linezolid
susceptible) due to in vitro synergy between tetracyclines concentrations, and long durations of therapy.151 Line-
and streptogramins and a lessening of the risk of zolid is currently reserved for the treatment of patients
selecting resistance.137 who either fail on or are intolerant of conventional
In a recent Australian study, 27 patients with staphyl- therapy. Like quinupristin/dalfopristin, linezolid is
ococcal bone and joint infections were treated with substantially more expensive than conventional therapy.
pristinamycin, because of patient intolerance or isolate
resistance to rifampicin and/or fusidic acid.138 Twenty- THERAPEUTIC DRUG MONITORING
four had MRSA, three coagulase-negative staphylococci, CONSIDERATIONS
and four multiple organisms. Pristinamycin monotherapy
was given in 19 cases. No haematological or biochemical Vancomycin
toxicity was observed; seven had gastrointestinal side- In the mid-1990s, a number of excellent reviews and
effects and one developed a rash, but only four required editorials called into question the age-old practice of
cessation of the drug due to side-effects. Treatment therapeutic drug monitoring (TDM) of vancomycin,
outcome was evaluated in 23 cases: 16 were cured and citing a lack of evidence for linking concentrations with
five were suppressed. Development of resistance was not toxicity or for improving the effectiveness or safety of
seen.The acquisition cost of pristinamycin to the authors vancomycin, and suggesting that empirical vancomycin
dosing regimens (e.g. nomograms that take account of occasionally for teicoplanin to ensure efficacy, especially
renal function and the patient’s age and weight) do not in patients who have high clearances, such as burns
compromise efficacy or safety compared with TDM- patients, children and injecting drug users.86 Trough
based dosing and are more cost-effective.85,152,153 concentrations should be >10 mg/L for most infections,
Currently, there is considerable variability in the utili- except endocarditis where they should be >20 mg/L.158
zation of TDM for vancomycin therapy at different Therapeutic drug monitoring of other antistaphylo-
hospitals, and its use is probably of most importance for coccal antibiotics such as β-lactams is not routine,
making sure that concentrations are adequate for although it is occasionally done for research purposes.
treating an infection.
The vancomycin MIC90 for staphylococci is 2 mg/L,
and maximal antibacterial effects occur with concen-
ANTIBIOTICS USED IN ‘HOSPITAL IN
trations 4–5 times the MIC in vitro. A number of THE HOME’ PROGRAMMES
investigators have shown that serum bactericidal titres Choice of therapy
(serum MBCs) of 1:8 (requiring serum drug concen-
trations of >12 mg/L in one cohort of 20 paediatric Selection of antimicrobials for use in a parenteral
patients)154 are necessary for clinical success.155 Thus, the ‘Hospital in the Home’ programme presents unique
targeting of trough plasma concentrations of 5 mg/L are challenges in addition to inpatient therapeutic consider-
of concern, especially for deep-seated staphylococcal ations. Of particular importance are the issues of
infections. Trough plasma concentrations >10–12 mg/L practicality and economics. For the management of
(which achieve concentrations >4–5 times the MIC and staphylococcal infections in particular, the short plasma
serum MBC titres of >1:8) would appear to be prudent, half-lives of most of the appropriate intravenous
but on the basis of tissue penetration may provide inad- β-lactams means that traditional dosing frequencies
equate local concentrations for some deep-seated are too cumbersome and impractical in the ‘Hospital in
infections. The most recent version (No. 12) of the the Home’ setting. In general, antibiotics given once or
Antibiotics Therapeutic Guidelines has adopted a target twice daily are most convenient and cost-effective for
trough vancomycin concentration of 10–20 mg/L, which home intravenous use, unless programmable pumps
is higher than in previous editions.36 are used, although this technology is relatively expen-
Recently, a 12-month retrospective review of MRSA sive. Hence, two approaches have been used to recruit
bacteraemias in a Melbourne teaching hospital revealed patients into such programs: the consideration of novel
that 9% were identified as hVISA, and that hVISA dosing strategies for short half-life β-lactams, and the use
episodes were more likely than MRSA episodes to occur of alternative antibiotics with longer half-lives (e.g.
in patients who had low trough serum vancomycin levels glycopeptides, ceftriaxone).
(<10 mg/L) during the first week of therapy.156 However,
it is yet to be determined whether dosing to trough Novel therapeutic approaches
concentrations >10 mg/L might improve the response to In recent years, consideration of pharmacokinetic and
hVISA infections or influence the emergence of pharmacodynamic relationships has led to the develop-
glycopeptide resistance. ment of a number of novel dosing strategies, making
Although there are reports of ototoxicity occurring outpatient parenteral treatment feasible for drugs that
with vancomycin, there is a paucity of data implicating would traditionally be considered inappropriate for such
the role of measuring serum vancomycin concentrations. a setting.
In a prospective study, the role of vancomycin alone in
causing nephrotoxicity was found to be very low, but Continuous infusion
nephrotoxicity increased to 22% to 35% with coadmin- Continuous infusions at concentrations above the MIC
istration of aminoglycosides.157 It is likely that high have been suggested to maximize the effectiveness of
vancomycin concentrations in many patients with renal those antibiotics that cause minimal suppression of
impairment may be more a consequence than a cause bacterial growth once concentrations fall below the MIC
of renal dysfunction. Overall, it is considered that (minimal persistent, sub-MIC or postantibiotic effects)
vancomycin monotherapy is unlikely to cause either and display time-dependent bacterial killing. The anti-
nephrotoxicity or ototoxicity, and the use of serum biotics most suited to this approach in dosing are the
concentrations to help identify actual or potential stable, short half-life β-lactams.159
toxicity has not been established.85 Despite the limita- A number of studies have shown that continuous
tions of the evidence linking concentration to toxicity, infusion of a short half-life β-lactam demonstrated
one should be cognizant of the possibility that use of comparable efficacy versus intermittent dosing, with a
larger doses to achieve higher trough concentrations reduced total daily dose and potential cost savings. Such
might increase toxicity. studies have included ceftazidime for pseudomonal
infections in cystic fibrosis patients160 and nosocomial
Other drugs pneumonia,161,162 and cefuroxime for a variety of infec-
Assays are available for the quantification of a variety of tions, including pneumonia.159 Improved efficacy has yet
antibiotics used to treat staphylococcal infections in to be noted with continuous infusions, since most
plasma and other biological fluids in some specialist studies have involved small numbers of patients and have
institutions. Therapeutic drug monitoring is performed mostly used intermittent regimens that are predicted to
produce adequate concentrations, and no differences in broad-spectrum cephalosporins. Diagn Microbiol Infect Dis
toxicity have been demonstrated. Continuous infusion of 1995; 22: 89–96.
flucloxacillin may be an alternative for the outpatient 3 Craig WA, Ebert SC. Killing and regrowth of bacteria in
vitro: a review. Scand J Infect Dis Suppl 1990; 74: 63–70.
management of staphylococcal infections,163,164 and it
4 Nimmo GR, Bell JM, Mitchell D, Gosbell IB, Pearman JW,
is usually given by a disposable infusion device or Turnidge JD. Antimicrobial resistance in Staphylococcus
programmable pump. However, the cost of these devices aureus in Australian teaching hospitals, 1989–1999. Microb
means they are usually reserved for the management of Drug Resist 2003; 9: 155–60.
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Probenecid has also been used to prolong the plasma and dicloxacillin. Br Med J 1970; 4: 455–60.
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tubular secretion component to their elimination165 by Med Protect J 2000; 1: 5–6.
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For example, the half-life of benzylpenicillin is increased Drug Evaluation Committee (ADRAC) Commonwealth of
by 2.6-fold in the presence of probenecid.166 The clinical Australia. A comparison of flucloxacillin with dicloxacillin.
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11 McNeil JJ, Grabsch EA, McDonald MM. Postmarketing
The decrease in total clearance (and consequent increase surveillance: strengths and limitations. The flucloxacillin-
in half-life) of the β-lactam is advantageous since it will dicloxacillin story. Med J Aust 1999; 170: 270–3.
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ACKNOWLEDGEMENTS amoxycillin-clavulanic acid associated jaundice. Med J Aust
1995; 162: 638–40.
The authors would like to thank: the Australian Society for Antimicro-
bials and Australasian Society for Infectious Diseases, who provided all 18 Dash CH. Penicillin allergy and the cephalosporins.
the financial support for the costs of production and publication of this J Antimicrob Chemother 1975; 1: 107–18.
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tiansen of the Australian Society for Antimicrobials, for devising the antibiotics commonly used in children. Pediatr Infect Dis J
concept of writing guidelines for the treatment of deep-seated staphy- 1995; 14: 221–31.
lococcal infections and for assistance with various aspects of 20 Fong IW, Engelking ER, Kirby VMM. Relative inactivation
publication; Associate Professor Iain Gosbell, Department of Micro- by Staphylococcus aureus of eight cephalosporin antibiotics.
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Service, Liverpool, NSW, for convening the ASA Staphylococcus aureus
21 Quinn EL, Pohlod D, Madhavan T, Burch K, Fisher E, Cox F.
Working Party and co-ordinating the writing of the body of
manuscripts and editing this manuscript; Mr Trevor Speight, Medical Clinical experiences with cephazolin and other
Editor, Medicines Information Co. Ltd, Auckland, NZ, for final editing cephalosporins in bacterial endocarditis. J Infect Dis 1973;
and formatting of this manuscript; and the members of the 1328 Suppl: S386–9.
Australasian Society for Infectious Diseases who provided peer review 22 Nannini EC, Singh KV, Murray BE. Relapse of type A beta-
of this work. lactamase-producing Staphylococcus aureus native valve
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Internal Medicine Journal 2005; 35: S3-S16

Antibiotics currently used in the treatment of infections

Abstract typically multi-resistant (mrMRSA), and mrMRSA

INTRODUCTION This review discusses the efficacy and adverse effect

Internal Medicine Journal 2005; 35: S3–S16

Table 1 Usual adult dosages of selected antistaphylococcal antibiotics†

Antibiotic Adult dosage/route of administration

Agents active against non-multiresistant MRSA strains (nmrMRSA)‡

product information for further details.

§mrMRSA = resistant to 3 or more non-β-lactam agents.

IV, intravenous; MRSA, methicillin-resistant S. aureus; PO, oral.

Internal Medicine Journal 2005; 35: S3–S16

Internal Medicine Journal 2005; 35: S3–S16

Internal Medicine Journal 2005; 35: S3–S16

Internal Medicine Journal 2005; 35: S3–S16

Internal Medicine Journal 2005; 35: S3–S16

Internal Medicine Journal 2005; 35: S3–S16

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