Infections
BMJ 2006; 332 doi: https://doi.org/10.1136/bmj.332.7545.838 (Published 06 April 2006) Cite this as: BMJ 2006;332:838All rapid responses
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While the article by Drs Healy and Freedman provided a concise and
authoritative summary of the management of infection in wound care, we
were disappointed to note in the section on osteomyelitis that the authors
recommend the use of the “probe to bone” test in diagnosis. We believe
that this test has acquired an unjustified position in clinical diagnosis
- based more on the simplicity of the concept than on its scientific
validity.
The evidence is based on a single study1 in which the sensitivity,
specificity, positive and negative predictive values (PPV and NPV) were
reported to be 66%, 85%, 89% and 56%, respectively, for the diagnosis of
osteomyelitis. However, this work has been criticised because of the high
prevalence of osteomyelitis (66%) in the small cohort (of hospital in-
patients with overt infection) tested 2. Calculations of sensitivity,
specificity, PPV and NPV are dependent on the prevalence of active disease
in the sample studied and the prevalence in this cohort was extremely
high. The “probe to bone” test was never evaluated in an independent
sample.
We have recently published our own findings3 in a population with a
lower pre-test probability of disease. We studied 81 consecutive patients
(with a total 104 foot ulcers) attending a specialist out-patient diabetic
foot clinic. A total of 21 ulcers (20.2% of 104) were associated with
osteomyelitis. The ‘probe to bone’ test was positive in 8 of these 21
ulcers, but was also positive in 7 of the 83 without associated bone
infection (sensitivity 38%, specificity 91%). While the NPV was 85%, the
PPV (the probability that a patient with a positive test would have
osteomyelitis) was only 53%. In a population with an even lower pre test
probability of osteomyelitis, such as in primary care or a podiatry based
clinic, the performance of the test is likely to be worse.
There is a danger that clinicians who place uncritical reliance on
the use of the “probe to bone” may diagnose osteomyelitis when it does not
exist, and this can lead to inappropriate antibiotic use, with the
associated problems of costs and the evolution of multi-resistant
organisms. Rather than state (as they did) that the “diagnosis of
osteomyelitis should be considered in any … wound (especially in diabetes)
that can be probed to bone”, it would be more precise to say that the
diagnosis is unlikely in any wound that cannot be probed to bone.
1.Grayson ML, Gibbons GW, Balogh K, Levin E, Karchmer AW. Probing to
bone in infected pedal ulcers. A clinical sign of underlying osteomyelitis
in diabetic patients. JAMA 1995; 273: 721-3.
2.Wrobel JS, Connolly JE. Making the diagnosis of osteomyelitis. J
Amer Pod Med Assoc 1998; 88: 337-43.
3.Shone A, Burnside J, Chipchase S, Game F, Jeffcoate W. Probing the
validity of the probe-to-bone test in the diagnosis of osteomyelitis of
the foot in diabetes. Diab Care 2006; 29: 945.
Competing interests:
None declared
Competing interests: No competing interests
Yet again, another review article on wound infections with no mention
of the importance of nutrition! Nor the evidence that immune enhancing
immune nutrition can reduce infection rates in a variety of different
elective surgical patients! At least the article on necrotising fasciitis
included a hint .... malnutrition is indeed an important predisposing
factor and nutritional support is vital in any successful outcome from the
condition! Both points were not emphasised in the text but found in boxes
well away from the reader's immediate attention! I give up preaching my
gospel .... I shall just go back to my Australian diet (good food and a
lot of fish) and a couple of glasses of Shiraz!
Competing interests:
I have given lectures in the past funded by Novartis Nutrition
Competing interests: No competing interests
Dear Sir,
Healy B, Freedman A. ABC OF WOUND HEALING. Infections. BMJ Vol 332 8
Apr. 2006 p.838-841
I have read with great interest this summary article on wound
infection, but I
am deeply concerned to see that there is no mention of ‘biofilm’. A
‘Google’
search today for ‘Biofilm in Chronic Wounds’ reveals over 33,000 sites, a
number of which reveal the importance that the study of chronic wound
biofilm production, and its management, now holds in chronic wound care.
Biofilm formation in nature is ubiquitous, and is fine tuned to
resist adverse
environments. If it is true that even a small proportion of biofilm in
chronic
wounds is resistant to invasion by the host defensive cells, antibodies
and
antibiotics (whether topical or systemic), then laboratory research and
clinical
focussing must be directed to the better understanding of the biology of
these biofilms, and their eradication (1 – 3)
Maggot Débridement Therapy (MDT) has a number of beneficial effects
in
open wounds and ulcers, including the apparent digestion of established
biofilm, and suppression of its formation (4).
If active agents, such as the spectrum of enzymes exhibited in some
maggot
exo-secretions, could be identified, purified and used clinically as
topical
agents, this would be a major breakthrough in wound care. Further, if
such
agents could also be selectively used systemically, then this would give
us the
prospect that biofilm could be destroyed in situ, wherever it might form,
notably on the surface of surgically implanted devices, such as joint
replacements, heart valves, and pacemakers. This would then considerably
reduce the necessity for ‘salvage’ surgery, which currently demands the
exploration of the infected implant, its removal and excision of all
infected
material, and, where possible, the later replacement of the device.
Yours faithfully,
John C T Church MD FRCSE
Refs.
(1) Mertz PM. Feature: Cutaneous Biofilms: Friend or Foe. Wounds –
ISSN.
2003 May;15(5):129-132
(2) Edwards R, Harding KG. Bacteria and Wound Healing. Current Opin
Infect
Dis. 2004 Apr;17(2):91-6
(3) Percival SL, Bowler PG. Feature: Biofilms and Their Potential
Role in Wound
Healing. Wounds – ISSN. 2004 July; 16(7):234-240
(4) Chambers I, Woodrow S, Brown AP, Harris PD, Phillips D, Hall M,
Church
JCT, Pritchard DI. Degradation of extracellular matrix components by
defined
proteinases from the greenbottle larva Lucilia sericata used for the
clinical
debridement of non-healing wounds. British Journal of Dermatology
2003;148:14-23
Competing interests:
None declared
Competing interests: No competing interests
Proinflammatory cytokines, endotoxins and chemokines : Biomarkers for systemic infection due to wounds
Infections remain a major source of failed wound healing. Spectrum
of interaction between bacteria and host progresses from contamination,
colonization, critical colonization, local infection to life threatening
systemic infections resulting in sepsis, multiorgan failure and even death
[1]. Invasive burn wound infection is the main causative factor of
sepsis, septic shock and multiple organ dysfunction syndrome (MODS) in
extensively burned patients and is the principal cause of death. Despite
the impressive advance in our understanding of the basic mechanisms of
sepsis, mortality rates in burned patients associated with sepsis remains
high[2,3]. Little is known of the importance of endotoxaemia in the
pathogenesis of the post burn septic syndrome that may lead to MOF. The
correlation between plasma endotoxin levels and the progression of MOF
remains controversial. Several studies indicate that organ failure is the
leading cause of death in surgical patients. An excessive inflammatory
response followed by a dramatic paralysis of cell-mediated immunity
following major surgery appears to be responsible for the increased
susceptibility to subsequent sepsis. In view of this, most of the
scientific and medical research has been directed towards measuring the
progression and inter-relationship of mediators following major surgery
[4]. Blood mediator concentration often parallel the inflammatory process
and high levels of cytokines can be followed by severe organ dysfunction.
Certain proinflammatory cytokine levels such as the interleukins(TNF-
alpha, IL 1 beta, IL-6) can be used in predictive ways to correlate organ
failure in multiply injured patients. Although much more research must be
done, there is great promise in the study of cytokines through basic
science research and clinical trials.
Current medical practice assumes that the normal population as well
as the population of each disease category can be represented by a smooth
continuum. Consequences of this conceptual clinical paradigm include the
establishment of normal reference ranges, effective therapeutic drug doses
and tumour classification by histology and histogenesis alone. But
current assumptions are valid when disease classification leads to therapy
that approaches 100% effectiveness which is not the case because of
difference in germ line genetics, somatic genomics and cancer tumour
genetics. Conventional pharmacology is based on ED 50, the dose that is
effective for 50% of the population. This has the implication that
defined standard drug doses are only appropriate for 30-50% of the
population. It further erroneously assumes that linear adjustment of the
dose would make drugs effective for the entire population that is not the
case. Hence application of genomics and biomarkers in clinical practice
could optimize drug dosage according to the genetics and genomics of the
individual patient apart from early detection of life threatening
conditions like sepsis and multiorgan failure [5].
Due to their pivotal role in pathogenesis, cytokines and chemokines
are sensitive and specific markers of acute infections. Laboratory
profiling these mediators has been found useful for the diagnosis,
monitoring and prognosis of acute as well as chronic infections.
Currently, the analysis of these markers tend to be expensive due to the
cost of equipment and reagents, rigid because of inflexible test panels,
and can be technically demanding if reproducible and reliable results are
to be obtained. These constraints should soon be remedied, driven by the
continual demand for routine profiling of cytokines, endotoxins and
chemokines. We need to integrate our basic research along with early
detection of proinflammatory mediators (cytokines, endotoxins) as markers
for systemic infection due to wounds so that we can prevent the
progression of local infection to critical conditions like sepsis and
multiorgan dysfunction syndrome. Proinflammatory mediators can act as a
potential targets for future therapeutics and research.
sohailkhan1981@gmail.com
References:
1.Brendan Healy, Andrew Freedman. ABC of wound healing : Infections.
BMJ 2006;332:838-841
2.Yizhi Peng, Zhiqiang Yuan, Hongbin Li. Removal of inflammatory
cytokines and endotoxin by veno-venous continuous renal replacement
therapy for burned patients with sepsis. Burns 2005;31: 623-638
3.Yao Y.M., Sheng Z.Y, Tian H.M., Yu Y. The association of
circulating endotoxaemia with the development of multiple organ failure in
burned patients Burns 1995;21: 255-258
4.Pape, Hans-Cristoph, Griensven V, Martij, Rice, John et al.Major
Secondary Surgery in Blunt Trauma Patients and Perioperative Cytokine
Liberation: Determination of the Clinical Relevance of Biochemical
Markers. Journal of Trauma-Injury Infection & Critical Care 2001; 50:
989-1000
5.Lam C W K, Wong C K. Cytokines and chemokines as markers of acute
infection. Clinical Laboratory International 2006;30:16-19
Competing interests:
None declared
Competing interests: No competing interests