VOLUME 11 NUMBER 1 • MARCH 2014
33
SA JOURNAL OF DIABETES & VASCULAR DISEASE
REVIEW
Invasive
Staphylococcus aureus
infections in
diabetes mellitus
Lukman Hakeem, Robert BS Laing, Ivan Tonna, John G Douglas, Alexander R Mackenzie
Abstract
S
taphylococcus aureus
, the most virulent of the many
staphylococcal species, has remained a major cause
of morbidity and mortality despite the availability
of numerous effective anti-staphylococcal antibiotics.
S. aureus
causes disease through both toxin-mediated
and non-toxin-mediated mechanisms. This organism
is responsible for both healthcare-associated and
community-based infections ranging from relativelyminor
skin and soft tissue infections to severe life-threatening
systemic infections. Patients with diabetes mellitus are at
increased risk of invasive
S aureus
infections. This article
focuses on the spectrum of invasive
S aureus
infections
and discusses the clinical features, investigations and
management of these infections in patients with diabetes
mellitus.
Keywords:
antibiotics, bacteraemia, diabetes mellitus, invasive
infections,
S aureus
Introduction
Staphylococci are Gram-positive cocci that form grape-like
clusters on Gram stain. They are capable of prolonged survival on
environmental surfaces in varying conditions.
Staphylococcus aureus
is a part of the normal human flora. About 25–50% of healthy
persons may be persistently or transiently colonised.
1,2
The rate
of colonisation is higher among patients with insulin-dependent
diabetes, HIV infection, patients undergoing haemodialysis, and
individuals with skin damage. The anterior nares are the most
frequent site of human colonisation, although the skin (especially
when damaged), vagina, axilla, perineum, and oropharynx may also
be colonised. These colonisation sites serve as a reservoir of strains
for future infections, and persons colonised with
S. aureus
are at
greater risk of subsequent infection than uncolonised individuals.
S aureus
has an environment-resistant peptidoglycan cell wall
surrounded by a microcapsule that determines the serotype.
1
Of
the 13 capsular types, type 5 and 8 account for 85% of clinical
isolates.
3–6
The bacterium produces a battery of surface proteins
involved in host colonisation, several enzymes engaged in tissue
Corresponding author: Dr Lukman Hakeem
Infection Unit, Aberdeen Royal Infirmary, Ward 111, ECC, Foresterhill,
Aberdeen, AB25 2ZN, UK.
e-mail:
Robert BS Laing, Ivan Tonna, John G Douglas and
Alexander R Mackenzie
Infection Unit, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, UK
Previously published in:
Br J Diabetes Vasc Dis
2013;
13
(4): 164–177.
S Afr J Diabetes Vasc Dis
2014;
11
: 33–43
invasion, and a multitude of toxins.
1
These include cytolytic toxins,
exfoliative toxins, enterotoxins and toxic shock syndrome toxin-1
(TSST-1). The cytotoxins can lyse neutrophils, resulting in the
release of the lysosomal enzymes that subsequently damage
surrounding tissues. Staphylococcal scalded skin syndrome,
characterised by exfoliative dermatitis, is mediated by exfoliative
toxins. Staphylococcal enterotoxins are mostly associated with
food poisoning and pseudomembranous enterocolitis. TSST-1 is
responsible for menstruation-associated and nearly half of non-
menstruation-associated staphylococcal toxic shock syndrome.
7
Increased virulence shown by some of the community
acquired
S aureus
strains has been attributed to genes (
lukS-PV
and lukF-PV
) that encode the subunits of Panton-Valentine
leukocidin (PVL), a cytolytic toxin.
8
PVL has been associated with
both superficial and severe skin and soft-tissue infections and
necrotising pneumonia among community-acquired methicillin-
sensitive
S aureus
(CA MSSA) isolates and later among CA
methicillin-resistant
S aureus
(MRSA) organisms.
9–11
The escalation
in morbidity and mortality associated with PVL MRSA has
caused public health concern worldwide. To date most PVL
S aureus
strains in the UK have been MSSA, but a major problem
has emerged with CA MRSA in North America, most of which
produce PVL.
12
In the UK the genes encoding for PVL are carried
by < 2% of clinical isolates of
S aureus
submitted to the National
Reference Laboratory, whether MSSA or MRSA.
13
Taken together, these factors make
S aureus
one of the most
pathogenic of human organisms. The most important characteristic
of
S aureus
is its marked capacity for swift tissue invasion,
multiplication at the nidus of infection, and subsequent rapid
dissemination throughout the body.
3,14
The major host defence
against tissue invasion seems to be opsonophagocytosis, which is
inhibited by the polysaccharide capsule.
2
Also characteristic of
S aureus
is its ability to colonise a broad
range of host tissues and to persist intracellularly or in biofilms
formed on prosthetic materials or on human tissues.
14,15
Biofilm
formation determines the persistent character of
S aureus
foreign body-related infection, endocarditis, and osteoarticular
infection.
1,15,16
Several aspects of immunity are altered in patients with diabetes.
17
Polymorphonuclear leukocyte function is depressed, particularly
when acidosis is present. Leukocyte adherence, chemotaxis, and
phagocytosis may be affected. Antioxidant systems involved in
bactericidal activity may also be impaired.
17,18
Moreover studies on
mice have shown that defects in neutrophil apoptosis may contribute
to the chronic inflammation and the inability to clear staphylococcal
infections observed in diabetic patients.
19
All these factors increase
the risk of invasive
S aureus
infection in patients with diabetes.
Spectrum of infection
Worldwide
S aureus
is the most commonly identified agent
responsible for skin and soft tissue infection (SSTI.)
20
Localised
