A 76-year-old Caucasian lady with a past medical history of non-Hodgkin's (Follicular) lymphoma, secondary hypogammaglobulinemia, bronchiectasis with recurrent lower respiratory tract infections, and aortic stenosis presented acutely unwell, but not neutropenic, with one week of fever and productive cough. On the day of admission she had been found unresponsive.
On admission she had a Glasgow Coma Scale of 10/15, with eyes opening to speech. She was pyrexial (40.3°C) and tachycardic with a blood pressure of 148/91. An ejection systolic murmur was audible along with bibasal coarse crepitations.
Finger prick testing revealed hypoglycaemia which was treated with 50% dextrose with an increase in the blood glucose but no improvement in the patient's general condition. Electrocardiograph and chest X-ray did not show any acute abnormalities. Echocardiograms were performed on days 2 and 13 with no vegetations or evidence of infective endocarditis.
The patient underwent a computed tomography head scan on day one which was reported as being normal. A lumbar puncture was performed which obtained a visibly turbid cerebrospinal fluid (CSF) with a white cell count of 7600
cells per mm3
(95% neutrophils), a red cell count of 250
cells per mm3
, undetectable glucose level, and a protein level of 7.02
g/L. Gram stain of CSF revealed Gram-positive diplococci. Unfortunately there was no growth after 48 hours incubation of CSF, but blood cultures grew S. pneumoniae
(serotype 35F, ST7004) susceptible to penicillin (minimum inhibitory concentration = 0.012
mg/L), erythromycin (MIC = 0.06
mg/L), vancomycin (MIC < 1
mg/L), and ceftriaxone (MIC < 0.06
mg/L). Polymerase chain reaction of the CSF using a real-time multiplex assay to identify the lytA
gene confirmed the presence of pneumococci in CSF, and further PCR for the 7 Multilocus Sequence Typing (MLST) house keeping genes identified this also as an entirely new sequence type (ST7004) currently unique to this patient.
The patient was known to develop a rash when given penicillin and so was initially treated with intravenous ceftriaxone 2
g twice daily and vancomycin 750
mg twice daily. Dexamethasone 2.5
mg four times daily was added orally on day 2 for a 4 day course. On day 6 treatment was rationalised to ceftriaxone 2
g twice daily alone on which the patient remained until discharge on day 15 having made a full recovery with no neurological deficit.
Eight months previously this patient had required admission for sepsis while recovering from Influenza A H1N1 (2009) and was found to have left basal pneumococcal pneumonia with septicaemia due to a vaccine preventable serotype (serotype 7F, ST191) treated initially with clarithromycin then levofloxacin. Prior to both episodes of invasive pneumococcal disease (IPD) she had received Pneumovax II (Sanofi Pasteur). We assessed her antibody response to the pneumococcal serotypes present in Pneumovax II using indirect immunofluorescence with anti-human immunoglobulin which indicated a poor response to many serotypes including 7F () in keeping with her known secondary hypogammaglobulinemia.
Table 1 Patient's response to Pneumovax II determined by indirect immunofluorescence with anti-human immunoglobulin. Poor response indicates a level below that believed to be protective and intermediateandindicates a response that is likely to be protective but (more ...)
Given the failure to respond to vaccination as a likely consequence of hypogammaglobulinemia and the predisposition this has given to recurrent IPD this patient now receives transfusions of 20
g normal human immunoglobulin (Kiovig, Baxter) every 3 weeks to prevent further reinfection. Prophylactic daily erythromycin has been commenced, and this patient is offered yearly seasonal influenza vaccination.