SA JOURNAL OF DIABETES & VASCULAR DISEASE
REVIEW
VOLUME 11 NUMBER 1 • MARCH 2014
37
be visible in the first 2 weeks in half of patients.
49
Paravertebral
abscesses involving the psoas muscle may be identified with
contrast. CT scans are also used to guide disc biopsy or drainage of
paravertebral collections.
49
Radionuclide imaging may also prove helpful in diagnosing
osteomyelitis and spondylodiscitis. Technetium-99m-methylene
diphosphonate bone scintigraphy and Gallium-67 scintigraphy
have a similar sensitivity of around 90% for the detection of discitis,
particularly in early disease.
34,49
Fluorine-18 fluorodeoxyglucose
positron emission tomography (FDG-PET) is showing promise as a
very sensitive modality. It can effectively distinguish infection from
degenerative changes even when MRI is inconclusive.
34,52
MRI is the most sensitive and specific modality for early
detection of osteomyelitis and pyogenic spondylodiscitis. It is the
modality of choice for the radiological diagnosis of spondylodiscitis
and has a reported sensitivity of 96%, specificity of 93% and
accuracy of 94%.
34
Its advantage over other modalities lies with
its superior ability to provide anatomical information, particularly
relating to the epidural space and spinal cord. It also allows
optimal assessment of any compression of neural elements.
Magnetic resonance imaging (MRI) is also recommended for
diabetic foot infections when soft tissue abscess or osteomyelitis
is suspected. Gadolinium enhancement improves the accuracy
of MRI, particularly in early infections when other changes may
be subtle.
34,49,53
MRI is not generally of value in prosthetic joint
infection due to metal artefact.
51
Antibiotic management
Antibiotic therapy, source identification and clearance and
appropriate surgical intervention are the basis of treatment for
invasive staphylococcal infections. The emergence of strains
with resistance to multiple agents has however complicated the
choice of empirical therapy. In addition to methicillin sensitive and
resistant strains of
S aureus
, the emergence of strains of MRSA
with the van A gene which show raised minimum inhibitory
concentrations (MICs) for glycopeptides implying clinical resistance
to vancomycin and teicoplanin is a cause for concern.
54
The source
of the van A gene is uncertain but there are cases which suggest
transfer from other Gram-positive organisms.
54,55
Most isolates
are however resistant by non-transferable mechanisms.
56
Reduced
susceptibility to vancomycin in vancomycin-intermediate
S aureus
(VISA) isolates is due to the synthesis of an unusually thickened
cell wall containing dipeptides capable of binding vancomycin,
thereby reducing availability of the drug for intracellular target
molecules.
57
Heteroresistant vancomycin-intermediate
S aureus
(hVISA) refers to VISA strains in which subpopulations of bacteria
display variable rather than uniform susceptibility to vancomycin,
but the vancomycin MIC for the entire population of the strain
remains within the susceptible range. Like VISA strains, hVISA
populations have an unusually thickened cell wall.
57
Delay in the administration of appropriate antibiotic therapy and
persistent bacteraemia after 72–96 hours of appropriate therapy,
has been associated with an increased risk of complications
and higher mortality.
2,58
Table 1 summarises the management of
invasive
S aureus
infections.
Penicillinase-stable penicillins such as flucloxacillin, are
recommended for MSSA infections. According to most recent
guidelines the minimum duration of treatment for uncomplicated
S aureus
bacteraemia is 14 days.
59
Several studies have shown that
the prognosis of invasive MSSA infection treated with vancomycin
is worse than for patients treated with
β
-lactams.
30, 60
Vancomycin, a glycopeptide that inhibits cell wall, synthesis is
the treatment of choice for MRSA bacteraemia. Despite extensive
experience and evidence underlying the use of vancomycin, it is far
from an ideal drug due to poor tissue penetration, slow bactericidal
activity, inconvenient administration and side effects.
30,61
In
particular, penetration is limited for bone, lung epithelial lining fluid
and cerebrospinal fluid.
62
The relationship between vancomycin
MIC and patient outcome in infections caused by vancomycin
susceptible strains is controversial, with some, but not all, recent
studies finding associations between higher vancomycin MIC
values (1.5 or 2.0 μg/ml) and worse prognosis.
30,63–65
Latest British
Society for Antimicrobial Chemotherapy (BSAC) guidelines on IE
however recommend MIC values to be established on chosen
antibiotics.
40
Teicoplanin, another glycopeptide, can also be used in the
treatment of
S aureus
(MSSA and MRSA) infections. Several studies
have shown that teicoplanin is as effective as vancomycin in the
treatment of bacteraemia and bone and joint infections and is
generally better tolerated with fewer adverse events.
66
Teicoplanin
has an advantage in terms of its single daily dosing and could also
be used three times weekly after appropriate loading for patients
suitable for out-patient parenteral antimicrobial therapy (OPAT).
Linezolid is a bacteriostatic, synthetic oxazolidinone, that
inhibits initiation of protein synthesis at the 50S ribosome.
30
Linezolid has good penetration into bone and excellent oral
bioavailability, characteristics that are desirable in the treatment
of bone infections.
67
Based on a number of clinical trails there
is evidence suggesting that linezolid is comparable to standard
antibiotic therapy in the treatment of
S aureus
infections.
30,68,69
Reversible myelosuppression is a potential serious adverse event
associated with linezolid therapy, especially with long term use.
Other reported adverse events include lactic acidosis, ocular
toxicity and peripheral neuropathy and a serotonin-like syndrome
when co-administered with serotonergic agents.
62,70
Daptomycin is a cyclic lipopeptide with rapid bactericidal
activity against
S aureus
.
30
Daptomycin was non-inferior to
standard therapy in studies, in the treatment of
S aureus
bacteraemia, IE, and complicated skin and soft tissue infections
due to MRSA infection.
62,1
Promising data on daptomycin use in
bone infections were reported in a recent systematic review of
uncontrolled case series.
72
Patients receiving daptomycin should be
evaluated regularly for clinical evidence of peripheral neuropathy
and myopathy. Serum creatine kinase (CK) should be monitored
at least weekly. It has also been associated with eosinophilic
pneumonia.
62,73
Generally daptomycin is a well tolerated antibiotic
that has the advantage of once daily dosing which also make it
suitable for OPAT.
74
It should not be used for cases of pneumonia
because it is inactivated by pulmonary surfactant.
75
Of concern
however is treatment-emergent resistance.
75
Tigecycline is a glycylcycline antibiotic with a bacteriostatic
effect on Gram-positive bacteria including
S aureus
. It can be used
for complicated skin, soft tissue and intra-abdominal infections. It
is effective against MRSA and extended-spectrum beta-lactamase
producing enterobacteriaeceae. Due to concerns regarding achiev-
ing adequate tigecycline serum drug concentrations, caution
should be used with tigecycline for the treatment of patients with
bacteraemia. Tigecycline has not been associated with any organ
toxicity or severe adverse events.
30,76
