Interferon-gamma Release Assay-positive Granulomatous Interstitial Nephritis in a Patient with a History of Diffuse Large B Cell Lymphoma.

Tuberculosis is a common etiology of granulomatous interstitial nephritis (GIN). However, the absence of evidence of lung involvement and lack of mycobacterial isolation in cultures make the etiological diagnosis and treatment decision challenging. We herein report a 46-year-old man with severe renal failure, a persistent fever, and a history of lymphoma. A renal biopsy exhibited GIN. Despite no evidence of tuberculosis except for a positive interferon-gamma release assay (IGRA), the patient was successfully treated with anti-tuberculosis drugs. Our case suggests that anti-tuberculosis therapy should be considered for patients with IGRA-positive GIN after excluding other etiologies.

Increased Vancomycin Clearance in Patients with Solid Malignancies.

Vancomycin (VAN) is an anti-microbial agent used to treat a number of bacterial infections, which has a high incidence of nephrotoxicity. We examined the pharmacokinetics of VAN retrospectively based on trough concentrations at large scale and identified pharmacokinetic differences between Japanese patients having solid malignancy and non-malignancy patients. Data were analyzed from 162 solid malignancy patients and 261 non-malignancy patients, including the patient's background, VAN dose, and pharmacokinetics of VAN. We failed to detect differences in values for VAN clearance or shorter elimination half-lives between these two groups. In contrast, multiple regression analysis under adjusting for confounding factors by propensity score, showed that VAN clearance significantly increased in relation to solid malignancies in each stage. We conclude that VAN clearance in solid malignancy patients is increased and that the blood concentration of VAN becomes lower than expected. These results suggest that early monitoring of VAN levels in solid malignancy patients might be essential for maintaining desired effects without side-effects.

Metastatic infection during Staphylococcus aureus bacteremia.

Staphylococcus aureus causes various infections, including skin and soft tissue infections and pneumonia via both, community-associated and nosocomial infection. These infectious diseases can lead to bacteremia, and may subsequently result in metastatic infections in several cases. Metastatic infections are critical complications in patients with S. aureus bacteremia, since the optimal duration of the antimicrobial treatment differs in patients with and without metastatic infection. Notably, two weeks of antimicrobial treatment is recommended in case of uncomplicated S. aureus bacteremia, whereas in patients with S. aureus bacteremia-associated endocarditis or vertebral osteomyelitis, six weeks of antimicrobial administration is vital. In addition, misdiagnosis or insufficient treatment in metastatic infection is associated with poor prognosis, functional disability, and relapse. Although echocardiography is recommended to examine endocarditis in the patients with S. aureus bacteremia, it remains unclear which patients should undergo additional examinations, such as CT and MRI, to detect the presence of other metastatic infections. Clinical studies have revealed that permanent foreign body and persistent bacteremia are predictive factors for metastatic infections, and experimental studies have demonstrated that the virulence factors of S. aureus, such as fnbA and clfA, are associated with endocarditis; however, these factors are not proven to increase the risk of metastatic infections. In this review, we assessed the incidence, predictive factors, diagnosis, and treatment for metastatic infections during S. aureus bacteremia.

Augmented Renal Clearance of Vancomycin in Hematologic Malignancy Patients.

The pharmacokinetics of vancomycin (VAN) was retrospectively examined based on trough concentrations at large scale to identify pharmacokinetic differences between Japanese hematologic malignancy and non-malignancy patients. Data from 261 hematologic malignancy patients and 261 non-malignancy patients, including the patient's background, VAN dose, and pharmacokinetics of VAN estimated by an empirical Bayesian method, were collected and analyzed. Our results showed significantly higher values for VAN clearance and shorter elimination half-lives in patients with hematologic malignancies than non-malignancy patients. In addition, multiple regression analysis under adjusting for confounding factors by propensity score, showed that VAN clearance significantly increased in relation to hematologic malignancies. In conclusion, since in hematologic cancer patients VAN clearance is increased, the blood concentration of VAN becomes lower than expected and this may contribute to the survival of resistant bacteria when VAN is administered at low doses. These results suggest that early monitoring of VAN levels in hematologic cancer patients might be recommended to maintain desired effects without side-effects.

Associations of HIV testing and late diagnosis at a Japanese university hospital.

OBJECTIVES: This study was conducted to clarify the rate of late diagnosis of HIV infection and to identify relationships between the reasons for HIV testing and a late diagnosis. METHODS: This retrospective cohort study was conducted among HIV-positive patients at the Jikei University Hospital between 2001 and 2014. Patient characteristics from medical records, including age, sex, sexuality, the reason for HIV testing and the number of CD4-positive lymphocytes at HIV diagnosis, were assessed. RESULTS: A total of 459 patients (men, n=437; 95.2%) were included in this study and the median age at HIV diagnosis was 36 years (range, 18-71 years). Late (CD4 cell count <350/mm3) and very late (CD4 cell count <200/mm3) diagnoses were observed in 61.4% (282/459) and 36.6% (168/459) of patients, respectively. The most common reason for HIV diagnosis was voluntary testing (38.6%, 177/459 patients), followed by AIDS-defining illness (18.3%, 84/459 patients). Multivariate analysis revealed a significant association of voluntary HIV testing with non-late and non-very-late diagnoses and there was a high proportion of AIDS-defining illness in the late and very late diagnosis groups compared with other groups. Men who have sex with men was a relative factor for non-late diagnosis, whereas nonspecific abnormal blood test results, such as hypergammaglobulinemia and thrombocytopenia, were risk factors for very late diagnosis. CONCLUSIONS: Voluntary HIV testing should be encouraged and physicians should screen all patients who have symptoms or signs and particularly hypergammaglobulinemia and thrombocytopenia, that may nonspecifically indicate HIV infection.

Associations of HIV testing and late diagnosis at a Japanese university hospital

OBJECTIVES: This study was conducted to clarify the rate of late diagnosis of HIV infection and to identify relationships between the reasons for HIV testing and a late diagnosis. METHODS: This retrospective cohort study was conducted among HIV-positive patients at the Jikei University Hospital between 2001 and 2014. Patient characteristics from medical records, including age, sex, sexuality, the reason for HIV testing and the number of CD4-positive lymphocytes at HIV diagnosis, were assessed. RESULTS: A total of 459 patients (men, n=437; 95.2%) were included in this study and the median age at HIV diagnosis was 36 years (range, 18-71 years). Late (CD4 cell count <350/mm3) and very late (CD4 cell count <200/mm3) diagnoses were observed in 61.4% (282/459) and 36.6% (168/459) of patients, respectively. The most common reason for HIV diagnosis was voluntary testing (38.6%, 177/459 patients), followed by AIDS-defining illness (18.3%, 84/459 patients). Multivariate analysis revealed a significant association of voluntary HIV testing with non-late and non-very-late diagnoses and there was a high proportion of AIDS-defining illness in the late and very late diagnosis groups compared with other groups. Men who have sex with men was a relative factor for non-late diagnosis, whereas nonspecific abnormal blood test results, such as hypergammaglobulinemia and thrombocytopenia, were risk factors for very late diagnosis. CONCLUSIONS: Voluntary HIV testing should be encouraged and physicians should screen all patients who have symptoms or signs and particularly hypergammaglobulinemia and thrombocytopenia, that may nonspecifically indicate HIV infection.

Predictive factors for metastatic infection in patients with bacteremia caused by methicillin-sensitive Staphylococcus aureus.

BACKGROUND: Metastatic infections such as infective endocarditis and psoas abscess are serious complications of Staphylococcus aureus bacteremia because failure to identify these infections may result in bacteremia relapse or poor prognosis. In the present study, we determined the predictive factors for metastatic infection due to methicillin-sensitive S. aureus bacteremia. METHODS: A retrospective cohort study was conducted among patients with methicillin-sensitive S. aureus bacteremia at the Jikei University Hospital between January 2008 and December 2012. Factors analyzed included the underlying disease, initial antimicrobial treatment and primary site of infection. RESULTS: During the 5-year study period, 73 patients met the inclusion criteria and were assessed. The most common primary site of bacteremia was catheter-related bloodstream infection (25/73 [34.2%]). Metastatic infection occurred in 14 of 73 patients (19.2%) (infective endocarditis [3], septic pulmonary abscess [3], spondylitis [4], psoas abscess [4], epidural abscess [3] and septic arthritis [1]). Six patients had multiple metastatic infections. Multivariate analysis revealed that the predictive factors associated with the development of metastatic infection were a delay in appropriate antimicrobial treatment of >48 hours, persistent fever for >72 hours after starting antibiotic treatment and lowest C-reactive protein levels of >3 mg/dL during 2 weeks after the onset of bacteremia. CONCLUSIONS: This study demonstrated that additional diagnostic tests should be conducted to identify metastatic infection, particularly in patients with delayed antimicrobial treatment, persistent fever and persistently high C-reactive protein levels.

Clinical characteristics and risk factors for mortality in patients with bacteremia caused by Pseudomonas aeruginosa.

OBJECTIVE: The mortality rates for bacteremia due to Pseudomonas aeruginosa remain high. In our hospital, we performed retrospective analyses to determine risk factors for mortality among patients with bacteremia caused by P. aeruginosa. MATERIALS AND METHODS: This retrospective cohort study was conducted among adult patients with bacteremia due to P. aeruginosa at Jikei University Hospital. We analyzed factors, such as age, gender, underlying disease, initial antimicrobial treatment, and primary site of infection to determine which of these were predictive of mortality in patients with P. aeruginosa bacteremia. RESULTS: One hundred and thirty-four patients with P. aeruginosa bacteremia were identified between April 2003 and March 2010. The 30-day mortality rate among all patients with P. aeruginosa bacteremia was 20.9%. The most common underlying disease was leukemia (20.9%), and the most common primary site of infection was the urinary tract (24.6%). Seventy-one patients (65.7%) were treated with an appropriate initial antimicrobial regimen for P. aeruginosa bacteremia. However, these patients had similar 30-day mortality to that observed in patients not administered appropriate antibiotics. This study revealed that risk factors for the 30-day mortality were thrombocytopenia and polymicrobial P. aeruginosa bacteremia (p<0.01). CONCLUSION: Thrombocytopenia and polymicrobial bacteremia were associated with a greater incidence of 30-day mortality among patients with P. aeruginosa bacteremia. On the other hand, age, underlying disease, and inappropriate initial empirical antimicrobial treatment did not affect mortality.

Interleukin-1 deficiency in combination with macrophage depletion increases susceptibility to Pseudomonas aeruginosa bacteremia.

We evaluated the role of IL-1 during Pseudomonas aeruginosa bacteremia by intravenously injecting P. aeruginosa strain D4 into IL-1-deficient and WT mice. The two strains showed equivalent mortality rates. However, when the mice were pretreated with cyclophosphamide, bacteremia-induced mortality was significantly greater in the IL-1-deficient mice than in the WT mice (P < 0.01). We then investigated the role of neutrophils and macrophages in protecting IL-1-deficient mice from bacteremia by administering anti-Gr-1 antibody or liposomes containing dichloromethylene diphosphonate, respectively. After P. aeruginosa inoculation survival was significantly lower in the macrophage-depleted IL-1-deficient mice than in the WT mice. In contrast, neutrophil depletion did not have this effect. Compared to the macrophage-depleted WT mice, the macrophage-depleted IL-1-deficient bacteremic mice had higher bacterial counts in various organs 48 and 72 hr post-infection. They also had lower TNF-alpha, IL-6, and INF-gamma concentrations in their livers during the early phase of sepsis. Thus, IL-1 deficiency becomes disadvantageous during P. aeruginosa bacteremia when it is accompanied by immunosuppression, particularly when macrophage functions are seriously impaired.

Interleukin-1-deficient mice exhibit high sensitivity to gut-derived sepsis caused by Pseudomonas aeruginosa.

BACKGROUND: The role of interleukin (IL)-1 in infectious diseases is controversial; some investigators indicated an enhancing effect of IL-1 on host resistance whereas others demonstrated the protective role of IL-1 receptor antagonist in infection. We evaluated the role of endogenous IL-1 in gut-derived sepsis caused by Pseudomonas aeruginosa, by comparing IL-1-deficient mice and wild-type (WT) mice. METHODS: Gut-derived sepsis was induced by intraperitoneal injection of cyclophosphamide after colonization of P. aeruginosa strain D4 in the intestine. RESULTS: The survival rate of IL-1-deficient mice was significantly lower than that of WT mice (P<0.01). Bacterial counts in the liver, mesenteric lymph node and blood were significantly higher in IL-1-deficient mice than in WT mice. Tumor necrosis factor alpha and IL-6 in the liver were significantly higher in IL-1-deficient mice than in WT mice. In vitro, phagocytosis and cytokine production by macrophages were impaired in IL-1-deficient mice compared with WT mice. CONCLUSION: Our results indicate a critical role for IL-1 during gut-derived P. aeruginosa sepsis. The results also suggest that both impairment of cytokine production and phagocytosis by macrophages are caused by IL-1 deficiency and lead to impaired host response.

A case of renal sarcoidosis: a special reference to calcium metabolism as a diagnostic and the therapeutic implications.

Sarcoidosis is a systemic granulomatous disease of unknown etiology and is associated with a wide variety of renal disorders including nephrolithiasis, hypercalciuria, hypercalcemia, nephrocalcinosis, tubular defect, glomerulonephritis, and granulomatous interstitial nephritis. We report a case of renal sarcoidosis in which we could not detect any evidence of extrarenal involvements that was diagnosed by renal biopsy and abnormal calcium metabolism incompatible with chronic renal insufficiency. On laboratory findings, decreased creatinine clearance, proteinuria, hypercalcemia, hypercalciuria, and mildly elevated serum angiotensin-converting enzyme (ACE) were seen. Serum intact parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,alpha-25 vit D) were lower and higher than normal range, respectively, whereas the patient was already in chronic renal insufficiency. He was treated with oral corticosteroid. Serum ACE tended to fall, and 1,alpha-25 vit D level decreased with substantial fall of serum calcium and daily calcium excretion. In contrast, intact PTH increased slowly in accordance with a fall of serum calcium compatible with the level of renal impairment. Creatinine clearance and daily excretion of protein improved. The case reported here may propose that serial measurement of serum level of 1,alpha-25 vit D, calcium level, and magnitude of daily calcium excretion into urine is a simple and meaningful tool to detect the therapeutic response in sarcoidosis with abnormal calcium metabolism.