This paper by Pei Chia Eng et al from the Kings College Hospital in London published in the Royal Society of Medicine Magazine – Feb 2014 makes you wonder as to how we should deal with pyrexia of unknown origin. It is very relevant in the present day when large doses of antibiotics are used sometimes unnecessarily.

A 45 year old woman presented to their hospital with one week history of intermittent fever with left flank pain, rigours and worsening knee pain. She had had revision right knee hemiarthroplasty a month before. Two out of 3 perioperative tissue samples at surgery grew coagulase negative staphylococci. She had been discharged with a peripherally inserted central catheter for a three month course of Teicoplanin and oral Rifampicin.

She was referred to the present team as the fever which initially appeared to settle down recurred again after 10 days. She was admitted for investigation and treatment. On investigation her temp was 38.5 deg, the CRP was 127mg/L and her neutrophil count was reduced. All other investigations including chest x-ray, abdominal ultrsound, trans thoracic echocardiogram for vegetation on the heart were all normal. The central venous line was removed and when checked for infection showed no growth in culture. Urine exam was positive for leucocytes and negative for nitrites. Urine culture grew Escherichia coli and blood cultures grew coagulase negative streotococci at 48 hrs.

With all these positive results pyelonephritis was suspected. She was therefore started on intravenous co-amoxiclav. Teicoplanin and Rifampacin were also continued. Following this the temperature seemed to range between 37.6 and 38.3 with occasional spikes. Although the patient appeared well the “C” reactive protein level kept going up. By this time as the orthopaedic surgeons decided that the knee was not infected the Teicoplanin and Rifampicin were discontinued.

Soon after this her inflammatory markers started to normalise. Although she remained well the temperature did not settle down to normal for a further 3 days. As she declined any further inpatient investigation she was discharged with a 2 week course of co-amoxiclav.

The whole picture seems very confusing to me. Did she have an infected knee in the first place. Were her symptoms and signs due to pylonephritis or endocarditis. Why did the C reactive protein level rise inspite of being on 3 different antibiotics and why did it start to come down as soon as Teicoplanin and Rifampicin were withdrawn.

The authors conclude that they cannot say for sure if infection was responsible for the patient’s symptoms when she came back to the hospital following her knee replacement. They have raised the query that drug fever as a differential diagnosis should be considered. The persistence of drug fever by Teicoplanin has been described sporadically in various case reports.

It would be interesting to hear the views of other members.