Dear Editor,

Co-trimoxazole for skin and soft tissue infections not responding to conventional oral antibiotics in Hong Kong

Patients with skin and soft tissue infections which do not respond to conventional oral antibiotic treatments are often referred to the hospital's Emergency Department. These commonly include cases of wound infection and cellulitis, and patients are often hospitalised for intravenous antibiotics. However, when there are no clear signs of systemic infection, especially in immunocompetent or healthy patients, admission may not be necessary if an appropriate trial of antibiotic regime adjustment is given.^1,2,3 Although co-trimoxazole would be regarded as an outdated antibiotic by most Hong Kong doctors, there is in fact strong evidence to support its use in this particular clinical context.

From my working experience in the Emergency Department, the patients with wound infection and cellulitis have typically been on antibiotics such as amoxicillin / clavulanate and/or cloxacillin, or cephalexin to cover against staphylococcus aureus and beta-haemolytic streptococci. When the patient may not show the usual features of Systemic Inflammatory Response Syndrome (based on temperature, heart rate, respiratory rate, white cell count) admission into hospital was usually not necessary.^1,2,3 Poor response to therapy may be because of antibiotic resistance due to community-associated methicillin-resistant staphylococcus aureus (CA-MRSA). International experts including those from the Infectious Diseases Society of America currently recommend co-trimoxazole as one of the antibiotics of choice when empiric coverage of CA-MRSA is considered.^1,2,3 In Hong Kong, the incidence of CA-MRSA is rising, with a study in 2009 showed that CA-MRSA was isolated from 13% of infected wounds and 17% of purulent cellulitis.⁴ Moreover, local data showed that CA-MRSA in Hong Kong is also sensitive to co-trimoxazole.⁵ At the author's hospital, data from our Antibiogram, January 1, 2016 - December 31, 2016 prepared by the hospital's Infection Control Team, 99% of staphylococcus aureus isolated from specimens from different hospital units in 2016 (n=1542) were susceptible to co-trimoxazole. By comparison, only 68% of these isolates were susceptible to cloxacillin.

For skin and soft tissue infections, lack of response to initial therapy should be followed by a collection of wound swab for culture and sensitivity, and the addition of a trial of co-trimoxazole for antibiotic therapy to cover against CA-MRSA. Streptococcal coverage with penicillins or cephalexin should be continued. The patient should be closely followed up to monitor for signs of systemic infection, and should be admitted if clinically indicated. If co-trimoxazole is contraindicated, doxycycline and minocycline are alternative choices of oral antibiotics for CA-MRSA, with minocycline use being supported by local data.^1,2,3,5 This approach can be utilised, not only by emergency department physicians, but also by primary care practitioners in the outpatient setting. For proven cases of CA-MRSA infection, decolonisation therapy is recommended.

Cautiously however, before prescription of co-trimoxazole, authoritative references should be consulted on drug interactions, adverse effects and contraindications. Of particular note, co-trimoxazole may cause hyperkalaemia, especially for the renal impaired and elderly patient, and it may potentiate the effect of other concomitant medications that may also cause hyperkalaemia. It may induce hypoglycaemia, and the drug is also contraindicated in pregnancy. Therefore, co-trimoxazole should not be used indiscriminately as a first-line antibiotic for uncomplicated skin and soft tissue infection. A recent randomised clinical trial showed that adding co-trimoxazole to cephalexin in uncomplicated cellulitis did not increase overall clinical cure rate, so it may not help every patient and further research may be needed to ascertain its effectiveness.⁶ In Hong Kong, Filipino ethnicity appears to be a risk factor for CA-MRSA and hence empiric addition of co-trimoxazole may be justified in such cases.⁴

Yours sincerely,
Stewart SW Chan, MBBS (Syd), FRCSEd, FRCEM, FHKAM (Emergency Medicine)
Senior Medical Officer, Accident & Emergency Department, Prince of Wales Hospital
Email: stewart_chan@hotmail.com / csw912@ha.org.hk