Ceftriaxone-induced Neurotoxicity in a Patient after Pancreas-Kidney Transplantation.

Ceftriaxone is a widely used third-generation cephalosporin showing advantageous pharmacokinetic properties and a broad antimicrobial spectrum. We herein report a case of ceftriaxone-induced neurotoxicity in a 56-year-old man on hemodialysis. Seven days after initiating high-dose ceftriaxone, the patient developed impaired consciousness along with facial myoclonus and sporadic phonation. The symptoms clearly disappeared shortly after withdrawal of the drug. Ceftriaxone is considered a safe antibiotic for patients with renal insufficiency, since it is excreted via both haptic and renal pathways. Physicians should note that antibiotic-associated encephalopathy may develop in patients administered ceftriaxone, especially in those complicated with renal dysfunction.

Correlation between outbreaks of multidrug-resistant Pseudomonas aeruginosa infection and use of bronchoscopes suggested by epidemiological analysis.

An outbreak of Multi-Drug Resistance Pseudomonas aeruginosa (MDRP) infections occurred in intensive care unit (ICU) and emergency room (ER) between June and August 2007. Five patients who isolated MDRP in the outbreak of 2007 were all used bronchoscopes, thus, we suspected contamination of the bronchoscopes as the cause of outbreak. Although we did not detect MDRP from any bronchoscopes, the outbreak finally ended after all the bronchoscopes had been disinfected appropriately with the reexamination of washing process in 2008 and 2009. We retrospectively reviewed eleven patients who isolated MDRP in 2006 and 2007, and the fact was revealed that bronchoscopes were used in most patients in ICU and ER. Bronchoscopes were significantly used during 2006-2007 period, compared with 2008-2009 period in ICU and ER, and the case-control analysis among all Pseudomonas aeruginosa isolated patients identified that bronchoscopes [risk ratio (RR) 8.25, 95% confidence interval (CI) 1.328-51.26] was one of the most important risk factors for MDRP isolation. Duration from admission to MDRP isolation was significant longer in MDRP-isolated cases (19.82±12.77 d), compared with in non MDRP-isolated controls (11.76±11.69 d: p=0.0453). Our epidemiological analysis suggested the significant risk factors for an MDRP outbreak, and could contribute the estimation of the focus and prevention of future outbreaks.

High-dose, short-interval daptomycin regimen was safe and well tolerated in three patients with chronic renal failure.

BACKGROUND: The recommended daptomycin dosage is 4 or 6 mg/kg/day for the treatment of complicated skin and soft tissue infections or for Staphylococcus aureus bacteremia, endocarditis, and osteomyelitis. Every other day administration is usually recommended for patients with mild to moderate renal impairment. Higher doses (>6 mg/kg/day) have been explored as a possible alternative. Daptomycin is considered a safe anti-methicillin-resistant S. aureus (MRSA) drug, although renal dysfunction may be worsened. In this paper we report on three patients with chronic renal failure who received a higher dose of daptomycin daily for successful treatment for MRSA bacteremia, MRSA osteomyelitis, and methicillin-resistant S. epidermidis (MRSE) endocarditis. RESULTS: Previous administration of other drugs, including vancomycin, teicoplanin, and linezolid, had failed. In spite of daily treatment with daptomycin instead of the recommended alternate day regimen, adverse effects, such as elevation of creatinine and creatine phosphokinase, did not occur. CONCLUSION: These experiences suggest that administration of high-dose/short-interval daptomycin can be efficient and safe even in the setting of renal dysfunction, and should be considered for the treatment of severe MRSA/MRSE infections in these patients.

Loading regimen required to rapidly achieve therapeutic trough plasma concentration of teicoplanin and evaluation of clinical features.

BACKGROUND: A trough concentration of >20 mg/L is considered the optimal dosage of teicoplanin required to ensure early therapeutic effects against methicillin-resistant Staphylococcus aureus (MRSA) infections including those in patients who develop febrile neutropenia after chemotherapy. This study determines appropriate initial doses during the first 2 days of administration and evaluates the therapeutic target teicoplanin trough concentration. METHOD: A 2-day regimen was evaluated in patients treated with 600 mg and 1200 mg or 1200 mg and 600 mg (total 1800 mg, Group 1), 800 mg and 800 mg (total 1600 mg, Group 2), and 800 mg and 400 mg (total 1200 mg, Group 3) of teicoplanin on Days 1 and 2, respectively. We also compared the efficiency and adverse effects at trough concentrations of 15-20 mg/L (Group A, n = 28) with >20 mg/L (Group B, n = 27) of teicoplanin, and also compared them with those on the similar concentrations of vancomycin (Groups C and D, n = 50 and 34, respectively). RESULTS: The mean trough concentrations of teicoplanin on Days 4 or 5 were 22.2, 17.5, and 16.2 mg/L in Groups 1, 2, and 3, respectively. The clinical efficiency was 85.7%, 81.5%, 92.0%, and 91.5%, in Groups A, B, C, and D, respectively. The rates of adverse effects were not high in teicoplanin (nephrotoxicity, 7.1% and 3.7%, and hepatotoxicity, 14.3% and 11.1% in Groups A and B, respectively). However, more adverse effects tended to arise in patients who received vancomycin in nephrotoxicity (14.0% and 11.8%, in Groups C and D, respectively). CONCLUSION: These results suggest that the 2-day regimens with total 1800 mg achieved the most effective therapeutic trough plasma concentration of teicoplanin (20 mg/L). However, 15-20 mg/L might also be an effective trough target for initial teicoplanin treatment. These teicoplanin regimens might be safer in terms of renal function than vancomycin.

Correlation between the consumption of meropenem or doripenem and meropenem susceptibility of Pseudomonas aeruginosa in a university hospital in Japan.

The appropriate use of carbapenems is essential in order to prevent resistance in Pseudomonas aeruginosa. We investigated the correlation between the consumption of meropenem or doripenem and the susceptibility of P. aeruginosa to meropenem in a Japanese university hospital from 2004 to 2009. The susceptibility data of P. aeruginosa and the annual consumption of meropenem or doripenem were analyzed. The consumption of meropenem or doripenem was calculated using the Anatomic Therapeutic Chemical classification and defined daily doses methodology. Meropenem consumption decreased and doripenem consumption increased and throughout the entire investigation period, total consumption of meropenem plus doripenem was stable. Although the annual number of isolated P. aeruginosa has not changed, the annual number of isolated multidrug resistant P. aeruginosa decreased by measures against nosocomial infection. The rate of meropenem resistant P. aeruginosa decreased in a time-dependent manner. Meropenem consumption was positively correlated with the meropenem resistance rate among P. aeruginosa (r = 0.9455, p<0.01). The total consumption of meropenem and doripenem was not correlated with the meropenem resistance rate (r = -0.6601, p>0.1). These results suggested that even if the total consumption of meropenem plus doripenem was not changed, meropenem susceptibility among P. aeruginosa improved by the decrease of meropenem consumption. Although meropenem and doripenem have been suggested to show cross-resistance with each other, the reduction of meropenem consumption might be effective for preventing an increase of meropenem-resistant P. aeruginosa.

Methicillin-resistant Staphylococcus aureus bacteremia at a university hospital in Japan.

Methicillin-resistant Staphylococcus aureus (MRSA) has become a leading cause of infections in hospitals, and mortality from MRSA bacteremia is high. In this study, we assessed the clinical characteristics and optimum management of 115 patients with MRSA bacteremia who were admitted to Osaka University Hospital between January 2006 and December 2010. Sixty-nine of the patients survived and 46 died of heart failure or renal failure. The nonsurvivors had reduced levels of platelets and albumin, and increased aspartate aminotransferase, total bilirubin, blood urea nitrogen, and creatinine levels. Other causes of death included sepsis, septic shock plus respiratory failure, disseminated intravascular coagulation, and unknown causes. However, a significant number of those whose infections were catheter-derived survived. Nonsurvivors were more often administered catecholamines and consultation with an infection-control team (ICT) was significantly associated with improved survival. Patients about whom the ICT were consulted were administered significantly more additional anti-MRSA drugs, for example trimethoprim-sulfamethoxazole, clindamycin, and gentamycin, than patients who were not the subject of consultation, although trough values for vancomycin did not differ between the two groups. Catheter removal was significantly higher for surviving patients with severe or complicated infections. These results suggest the status of patients with MRSA bacteremia who did not survive was worse than those who did survive, but that ICT consultation might significantly affect survival by recommendation of appropriate care and anti-MRSA drug use.

Impact of antimicrobial stewardship by infection control team in a Japanese teaching hospital.

The objective of this study is to investigate an effect on the antimicrobial appropriate use of the antimicrobial stewardship. We investigated the consumption of injectable antimicrobials from 2001 to 2007 and the administration period of specific antimicrobials (carbapenems, fourth-generation cephalosporins, anti-methicillin-resistant Staphylococcus aureus (MRSA) agents) in the individual patient. Since September 2004, the infection control team at Osaka University Hospital has been promoting appropriate use of antimicrobials through consultation, education, and weekly surveillance of specific antimicrobial usage. We obtained the amount of all antimicrobial injections as titer from the medical information database of the electronic medical chart system retrospectively. Antimicrobial use densities (AUD) were evaluated by measuring the number of doses administered/1000 patient-days. Although the number of inpatient admissions and operations increased 1.53- and 1.39-fold, respectively, in the seven years from 2001 to 2007, the expenditure on specific antimicrobials decreased markedly with AUD of specific antimicrobials decreasing from 39.6 to 29.2. The percentage of inpatients receiving specific antimicrobials decreased from 19.8% to 9.8%, and the ratio of the number of inpatients administered a specific antimicrobial within seven days to the number of inpatients administered each specific antimicrobial increased to over 60%. This led to reduction in the total expenditure of antimicrobials by about 100 million yen annually. The incidence of hospital-associated MRSA (HA-MRSA) infection decreased from 0.93% (2003) to 0.68% (2007). We can reduce the expenditure of antimicrobials without increasing incidence of the HA-MRSA by antimicrobial stewardship, and we think that appropriate use of antimicrobials is achieved progressively.

Evaluation of environmental contaminations and occupational exposures involved in preparation of chemotherapeutic drugs.

Many healthcare workers are concerned about the risk of occupational exposures to hazardous drugs. The Japanese Society of Hospital Pharmacists (JSHP) revised the "Guidelines for the Handling of Antineoplastic Drugs in Hospitals", however, the precautions and awareness of handling drugs varied in institutions. We assessed the levels of environmental contaminations in our hospital and urinary excretion of cyclophosphamide (CP) and ifosfamide (IF) in pharmacists and nurses. In environmental studies, we obtained samples by wiping the surfaces around two biological safety cabinets (BSCs) on eight days for four months. One BSC was equipped in hospital pharmacy and the other was equipped in an oncology ward, and used for preparing chemotherapeutic drugs for outpatients and for inpatients, respectively. We obtained the urine samples from 6 pharmacists and 2 nurses. We used solid phase extraction (SPE) as a convenient extraction procedure and liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) for the analysis of the samples. CP was detected on the working surfaces inside both BSCs, and detected at low levels on the back surfaces of the BSCs and at the working tables around the BSCs. IF over the LLOQ was not detected in both BSCs. CP and IF were not detected in all urine samples of pharmacists and nurses. Detection frequencies and amounts of these drugs were low levels, compared with previous reports in Japan, and our results showed that improving awareness about handling hazardous drugs could reduce the risk of the occupational exposures.