A Standard 5 boy returned from a summer camp with several minor cuts and abrasions. Within a week, extensive cellulitis developed, and it was apparent that subcutaneous tissue was involved, requiring surgical intervention of nonviable tissue.
A provisional diagnosis of cellulitis is made, blood samples are taken for culture, sensitivity and testing. The doctor prescribes intravenous Dicloxacillin 250mg qid for 5 days.
A short review of the aetiology of the disease indicated in the scenario
Cellulitis is a kind of skin infection that will affect the skin and subcutaneous tissues, eventually spread to other areas. It often occurs in many parts of the skin where the skin barrier is damaged which includes a cut, abrasions and scratches. Bacteria such as streptococcus pyogenes and staphylococcus aureus are the most common type of bacteria that cause cellulitis. However, Heamophillus influenza may be responsible for the development of cellulitis in children but is rare. Besides that Aeromonas hydrophila is also associated with cellulitis when a wound is immersed or prolonged in fresh water. An infection can occur when these microorganisms invade the broken surface of the skin and spread, resulting symptoms like pain, swelling and warmth at the site of infection. 1,2
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Staphylococcus aureus is a gram positive cocci with a spherical shape that resides on various skin surfaces without harming the host. Although it is harmless, but when there is a breach in tissue barrier the bacteria will get into the body resulting cellulitis especially around the legs, face or any other parts of body.3,4 The possible starting point of cellulitis are usually located at wounds or surgical incisions. Sense of feverish and sick will be developed when these area start to spread.4 Infections of Staphylococcus aureus from minor rashes to cellulitis, impetigo, scalded skin syndrome or even severe toxic shock syndrome are due to the its production of virulence factors. These factors include five cytolytic toxins known as alpha toxin, beta toxin, delta toxin, gamma toxin, Panton-Valentine toxin and two exfoliative toxins A and B. Both types of toxins are responsible for tissue damage such that the cytolytic toxins lyse neutrophils, causing the release of lysosomal enzyme that will damage the surrounding tissues while the exfoliative toxins cause tissue damage due to the release of cytokins by interacting with specific T-cell receptors that leads to proliferation of T cells.3
In addition, staphylococcus aureus can be transmitted through skin to skin contact. In this, case to prevent a standard five boy from infected, protective wear has to be worn to avoid injuries from the summer camp.5
Was the doctor's presumptive diagnosis justified? Describe how you reached this conclusion citing microbiological, symptomatic evidence and literature to support your argument
The causative microorganism in this case is known as Staphylococcus aureus after several tests have been carried out for confirmation. Firstly, the bacteria are stained purple which give a positive result in gram-staining procedure and appear as spherical shape with grapelike cluster arrangement when view under microscope. Besides that the bacteria also show positive result in catalase test which verifying that the bacteria are staphylococci species that produce catalase to degrades hydrogen peroxide into oxygen and water. These bacteria also give a positive result in coagulase test as they produce coagulase that convert prothrombin to thrombin resulting clot formation. These two definitive biochemical tests confirm the species to be staphylococcus aureus.6,7
On the other hand, the blood sample of the boy was sent to laboratory for culture on three different agar plates such that the Mannitol Salt Agar (MSA), blood agar with neomycin and blood agar with neomycin and bacitracin. Under aerobic conditions, only the MSA plate shows growth because Staphylococcus aureus only grow on mannitol salt agar plate as golden-$yellowish, round with smooth surface colonies. MSA is a selective and differential medium which is able to select out bacteria that can grow in high sodium chloride concentration medium since other bacteria are unable to tolerate such high levels of sodium chloride. It also contains phenol red which is an indicator to differentiate mannitol fermenters staphylococci from non- mannitol fermenter staphylococci. The phenol red will turn from red to yellow in response of acidic environment which is due to the lactic acid that is produced during the fermentation of mannitol by mannitol fermenter staphylococci such as staphylococcus aureus. Thus, the microorganism that is responsible in the infection is staphylococcus aureus.6,8
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Normally, staphylococcus aureus thrive underneath the skin's surface when the barrier is exposed and cellulitis will start with that small exposed area like a cut showing redness and also sensation of pain and warmth around the area will be experienced by the patient.9,10
Before the doctor's presumptive can be justified, careful examination and diagnosis on patient's signs, symptoms of the infections and his previous activity have to be done. First of all, the standard five boy probably infected because of the cut and abrasions on his body. These damaged areas on his skin are the most likely pathway for bacteria like staphylococcus which is the normal flora resides on his skin to invade into his body. In addition, he needs to undergo surgical intervention to remove nonviable tissue which the subcutaneous tissue is involved. According to these data, the boy may suffer from severe cellulitis which is also known as necrotizing fasciitis (NF) due to the same sign and symptoms shared. Based on the microbiological data and the symptomatic evidence of the patient, the doctor's presumptive of cellulitis is justified despite the possibility of developing NF.
Could the doctor's selection of antimicrobial therapy following the presumptive diagnosis be criticized? Would you have recommended any alteration in the initial therapy or in the subsequent treatment plan following the availability of the microbiological data? Justify your decision and make reference to the literature
According to the antibiotic minimum inhibitory concentration (MIC) testing, the results of four antibiotics namely oxacillin, fusidic acid, neomycin and dicloxacillin are obtained. The MIC for each antibiotic for staphylococcus aureus is shown in the table below.
Table 1: MIC results of antibiotics.
The standard 5 boy was given intravenous 250mg of Dicloxacillin, 4 times per day for 5 days by the doctor. In such severe cellulitis which necrotizing fasciitis is suspected, intravenous therapy with β-lactamase resistance penicillin is needed. Dicloxacillin is a narrow spectrum β-lactam antibiotic that is specific on staphylococcal species. It is bacteriacidal which is able to bind to penicillin binding proteins, which are enzymes responsible for the synthesis of cell wall peptidoglycan.3,7 As a result, the cross linkage of the peptide chains attached to the backbone of the peptidoglycan is inhibited, followed by inhibition of autolytic enzyme in the cell wall and result in lysis of the bacteria.11 Based on the MIC test, Dicloxacillin has second lowest MIC which is rather a good choice for staphylococcus aureus compare to oxacillin. This means that Dicloxacillin is more active toward strains of staphylococcus aureus at low concentration.12
Next, oxacillin is also a β-lactam antibiotic which is resistance to the penicillinase produce by staphylococcal species like staphylococcus aureus. Its action is same as the dicloxacillin which it exerts a bacteriacidal action against staphylococcus aureus during the state of active multiplication and inhibits its cell wall synthesis. However, it has a high MIC values obtained in the antibiotic susceptibility test. Despite its action which is highly specific towards staphylococcus aureus it is not commonly used as there are 30% to 50% of the strains of staphylococcus aureus are resistiant to oxacillin.3,13 Although staphylococcus aureus may developed resistance when treated with dicloxacillin but oxacillin resistance Staphylococcus aureus (ORSA) is more prevalent in hospital and community. It is also likely to cause adverse reaction like reversible hepatitis and rash.14
In addition, fusidic acid is a narrow-spectrum antibiotic which inhibits protein synthesis in bacteria by preventing translocation of growing peptide along the ribosome. It is highly active against Gram-positive bacteria such that the staphylococcus aureus and is useful in treating infection caused by penicillin resistance staphylococci. From the MIC table, it has the lowest MIC values but it has some adverse effects which is the gastrointestinal disturbance and skin eruptions. It is usually associated with second anti-staphylococcal antibiotic in clinical use to avoid emergence of resistance.10,11
Lastly, Neomycin is a broad-spectrum aminoglycoside antibiotic which is active against most Gram-negative and some Gram-positive bacteria. Like fusidic acid, neomycin inhibits bacteria protein synthesis and is widely used for skin or mucous membranes infections.10,11 With its high MIC value obtained from the susceptibility test, there is possibility that the incidence of nephrotoxicity increased when administered with β-lactam antibiotics, despite its effectiveness. Furthermore since it is a broad spectrum antibiotic, it is also not recommended as the confirmed bacteria causing the infection is staphylococcus aureus. A narrow spectrum antibiotic that targets staphylococcus aureus should be used instead.10,14
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In conclusion, the doctor's initial prescription which is dicloxacillin is a good choice of antibiotic since the bacteria that is causing the patient from suffering cellulitis without systemic symptoms is staphylococcus aureus. Alternatives which targeted on staphylococcus aureus like clindamycin, clarithromycin and cefazolin are recommended if the patient is allergic to dicloxacillin.10 In order to eradicate and prevent the recurrence of the infection, some changes can be made to the treatment plan such that the dicloxacillin can be replace with vancomycin only f the strains of staphylococcus aureus are resistance to methicillin wich is known as MRSA. Benzylpenicillin which is a type of penicillin should be given if systemic response developed in the patient instead of giving dicloxacillin.2 Prevention such that keeping good self hygene also helps to eliminate cellulitis permanently.5