Observational retrospective single-centre study in Japan to assess the clinical significance of serum daptomycin levels in creatinine phosphokinase elevation.

WHAT IS KNOWN AND OBJECTIVE: Daptomycin-induced creatinine phosphokinase (CPK) elevation is reported to be associated with its trough level (Ctrough ; breakpoint of 24.3 µg/mL). However, even with high-dose treatment (ie, > 8 mg/kg), the safety of daptomycin treatment is widely demonstrated with low or no significant incidence of CPK elevation or other adverse effects, despite the possibility of Ctrough above 24.3 µg/mL. Therefore, we questioned the clinical significance of Ctrough levels of 24.3 µg/mL. In this study, we retrospectively evaluated the significance of Ctrough in the clinical setting, in addition to completing a retrospective safety assessment of daptomycin utilizing electronic health records. METHODS: Patients who had received daptomycin treatment for > 4 days from July 2011 to June 2015 were enrolled. Serum daptomycin levels, including Ctrough and peak (Cpeak ), were measured by high-performance liquid chromatography equipped with a photodiode array. To evaluate the safety, patients' characteristics and relevant laboratory test values were reviewed retrospectively using an electronic medical record system. RESULTS AND DISCUSSION: A total of 52 therapeutic cases for 46 patients were identified; of these, Ctrough and Cpeak levels were measured in 27 and 28 cases, respectively, and 6 patients received multiple courses of daptomycin treatment. The median age of the 52 patients was 68 years (range: 19-88 years), and 14 patients initially had an estimated creatinine clearance of less than 30 mL/min. Seven cases indicated a Ctrough of above 24.3 µg/mL; however, none of these presented CPK elevation, which meets with the study definition for abnormality. Furthermore, of the two patients with abnormal CPK elevations, only one patient had a measured Ctrough (of 10.9 µg/mL). Their CPK abnormalities were temporal and did not result in treatment discontinuation. The other four patients discontinued daptomycin treatment due to suspicions of adverse effects. Of the discontinued patients, two had measured Ctrough levels; these were 8.6 and 8.1 µg/mL. All patients with abnormal CPK elevation or treatment discontinuation exhibited Ctrough levels lower than 24.3 µg/mL. In this study, two patients receiving high-dose daptomycin (ie, 9.4 and 10.0 mg/kg) had observed Ctrough levels similar to patients who received doses of daptomycin < 9 mg/kg. WHAT IS NEW AND CONCLUSIONS: The safety of daptomycin treatment was suggested in this study. Ctrough level of 24.3 µg/mL was not suggested as a significant clinical index for the incidence of CPK elevation, adverse effects or treatment discontinuation. Thus, acceptable tolerability towards higher Ctrough levels than 24.3 µg/mL was also suggested, though further studies are required. On the other hand, low levels of daptomycin in blood were unexpectedly observed in two cases, despite the high-dose treatments. Accordingly, the monitoring of serum daptomycin levels may also be useful to assess cases in which subtherapeutic levels were achieved.

Tuberculous arthritis of the hip with Staphylococcus aureus superinfection.

Skeletal tuberculosis (TB) accounts for a small percentage of all cases of TB. It is often difficult to diagnose, especially in the hip joint. TB arthritis can be masked by superinfection with other pathogens, leading to a delay in diagnosis and treatment. Trauma or surgery is a reported risk factor of TB arthritis. In contrast, descriptions of TB arthritis after a closed bone fracture are rare. We herein report a case involving an 81-year-old woman with septic arthritis superinfected with methicillin-resistant Staphylococcus aureus (MRSA) and Mycobacterium tuberculosis. Three months before presentation, she sustained a bone fracture of the left femur and was treated conservatively without surgery. She developed a fever at another hospital and was transferred to our institution. Computed tomography revealed the presence of abnormal fluid around the left hip joint. MRSA was detected from the fluid and blood cultures. The patient was diagnosed with MRSA arthritis and treated with antibiotics and surgical drainage. However, her fever persisted, and the abscess further developed and enlarged around the left hip. It was punctured and cultured again. Three weeks later, Mycobacterium tuberculosis was identified from the abscess culture. The septic arthritis was confirmed to have been caused by MRSA and M. tuberculosis. After the initiation of antituberculosis therapy, her fever subsided and the treatment was continued. This case demonstrates that the diagnosis of TB arthritis can be hindered by the existence of other pathogens and that TB arthritis can occur at a closed fracture site in the hip joint.

Community-acquired pneumonia caused by carbapenem-resistant Streptococcus pneumoniae: re-examining its prevention and treatment.

A 73-year-old man with no significant past medical history or any history of health care visits was hospitalized for pneumonia. Sputum culture revealed multidrug-resistant Streptococcus pneumoniae, even to carbapenems. The patient was later treated successfully with levofloxacin. Throat cultures from his two grandchildren revealed S. pneumoniae with the same susceptibility pattern. Analysis for resistant genes revealed gPRSP (pbp1a + pbp2x + pbp2b gene variants) in both the patient and his grandchildren, none of whom had received pneumococcal vaccines of any kind. This case illustrates the importance of the emergence of carbapenem-resistant S. pneumoniae. Non-rational use of carbapenems for community-acquired infections may be counterproductive. This case also highlights the importance of pneumococcal vaccinations in children and the elderly.