Severe hyperglycemia during renally adjusted gatifloxacin therapy

OBJECTIVE: To report a case of severe hyperglycemia in a nondiabetic patient receiving gatifloxacin that was properly dosed based on renal function. CASE SUMMARY: A 65-year-old nondiabetic female with progressive renal dysfunction was admitted for severe hyperglycemia. The patient had received 9 days of a 10-day course of renally adjusted therapy with gatifloxacin 200 mg/day for bronchitis. Her blood glucose level on admission was 1121 mg/dL, at which point the gatifloxacin was discontinued. After several days of intensive insulin therapy, the blood glucose levels returned to normal, and the patient was subsequently discharged. DISCUSSION: Gatifloxacin-induced hyperglycemia has been reported in the literature, but based on a MEDLINE search (1966-December 2004), no such cases were found in a nondiabetic patient receiving the proper gatifloxacin dose, adjusted for degree of renal insufficiency. The available case reports seem to suggest the increase in blood glucose concentrations could have been precipitated by high drug concentrations in patients not receiving the renally adjusted dose or in those with preexisting, undiagnosed diabetes. A definite mechanism of action for gatifloxacin-induced hyperglycemia is not known. The Naranjo probability scale revealed a probable adverse reaction of hyperglycemia associated with gatifloxacin therapy. CONCLUSIONS: Healthcare professionals should be more aware of the possible development of hyperglycemia in all patients taking gatifloxacin, including those who are not diabetic and those receiving appropriately reduced doses for renal dysfunction.     

Possible gatifloxacin-induced hyperglycemia

OBJECTIVE: To report a case of possible gatifloxacin-induced hyperglycemia in a nondiabetic middle-aged woman. CASE SUMMARY: A 64-year-old Indian woman with an extensive cardiovascular history was admitted for urosepsis. On admission, her blood glucose was 117 mg/dL. She was empirically started on gatifloxacin 400 mg/day; after 3 days of gatifloxacin therapy, her blood glucose was 607 mg/dL. On day 4, therapy was changed to cefazolin for sensitive Escherichia coli and her blood glucose levels began to return to normal. DISCUSSION: Although gatifloxacin has been previously reported as a potential cause of both hyper- and hypoglycemia, the exact mechanism is unknown. Several factors that may have been involved in our patient's hyperglycemia are discussed. She experienced hyperglycemic changes more rapidly than did the typical patients of previous reports. The Naranjo probability scale suggests a possible drug-related event. CONCLUSIONS: The temporal relationship between gatifloxacin administration and the patient's hyperglycemia suggests an iatrogenic cause. Based on our experience and the product labeling, clinicians should be more aware of the blood glucose-altering effects of gatifloxacin.     

Possible gatifloxacin-induced hypoglycemia

OBJECTIVE: To report a case of hypoglycemia in a patient receiving gatifloxacin for presumed exacerbation of chronic obstructive pulmonary disease (COPD). CASE SUMMARY: A 73-year-old white man with an extensive past medical history significant for type 2 diabetes mellitus and COPD was prescribed gatifloxacin 400 mg/d for a COPD exacerbation. After 2 days of therapy, the patient presented to the emergency department (ED) reporting worsening symptoms; he had a blood glucose concentration of 22 mg/dL. Because he had not eaten well for several days, the patient discontinued his oral antidiabetic medications prior to presenting to the ED, but continued to take gatifloxacin. The patient had never before experienced a symptomatic hypoglycemic episode during the years of taking his antidiabetic medications. In the ED, he received 1 last dose of gatifloxacin and was treated aggressively with intravenous dextrose. By the end of his hospitalization, antidiabetic medication was restarted to control hyperglycemia. DISCUSSION: Although gatifloxacin has been shown to alter glucose homeostasis, the mechanism of action has not been elucidated. Other recognized risk factors that contribute to the development of hypoglycemia are discussed. Our patient experienced hypoglycemia after receiving gatifloxacin and recovered 24 hours after discontinuation. The Naranjo probability scale suggests a possible drug-related event. CONCLUSIONS: The temporal relationship of gatifloxacin administration and the hypoglycemic episode suggests that gatifloxacin likely precipitated the event. Clinicians should be aware of this adverse effect in patients taking gatifloxacin presenting with hypoglycemia.     

Olanzapine-lnduced hyperglycemic nonketonic coma

OBJECTIVE: To report a case of olanzapine-induced hyperglycemia leading to a hyperosmolar, hyperglycemic, nonketonic coma. CASE SUMMARY: A 51-year-old, 85.5-kg (ideal body weight 79.9 kg), white man presented to a Veterans Affairs hospital with a serum glucose concentration of 1596 mg/dL. Soon thereafter, he went into a hyperosmolar, hyperglycemic, nonketonic coma. Olanzapine therapy had been instituted less than six months prior to this event; approximately two months before this event, his blood glucose was 108 mg/dL. Eight days after stopping olanzapine, the glucose concentration returned to normal, and the patient no longer required insulin nor any other glucose-lowering agents. DISCUSSION: The insulin resistance caused by olanzapine is normally attributed to the weight gain associated with the drug. In this patient, it appears that olanzapine caused hyperglycemia by a mechanism other than weight gain. CONCLUSIONS: This case report and others from the literature suggest that olanzapine therapy may induce hyperglycemia in some patients.     

A case of successful treatment of a patient with hyperglycemia of 2700 mg/dL

A 34-year-old man with obesity who was an avid consumer of soft drinks was found in a coma after complaining of a poor physical condition for a few days. On arrival, he had hyperglycemia of 2700 mg/dL, coma, shock, sepsis, aspiration pneumonia, acute renal failure, acute pancreatitis, liver dysfunction, and systemic mycosis. The rapid infusion of a large volume of isotonic saline, insulin, antibiotics, and ulinastatin was performed, and mechanical ventilation was applied. The treatment was complicated by transient hypernatremia resulting from osmostasis, which gradually decreased. He demonstrated transient decerebrate posturing upon stimulation; however, he became conscious within a week of admission, and his associated diseases also improved. After correcting his hyperglycemia, the patient was discharged on foot. We report our case of a patient with hyperglycemia of 2700 mg/dL, which was the highest value reported in the English literature. During the correction of the hyperglycemia, transient hypernatremia occurred to prevent abrupt decrease in osmolality, which thus resulted in cell swelling.     

Acute interstitial nephritis due to pantoprazole

OBJECTIVE: To describe what is believed, as of November 4, 2003, to be the first case published in the literature of acute interstitial nephritis (AIN) due to pantoprazole. CASE SUMMARY: A 77-year-old white woman presented to the hospital with elevated serum creatinine, oliguria for the past 24 hours, arthralgia, fatigue, fever, and bilateral flank pain. The patient had initiated treatment with oral pantoprazole 40 mg/d for gastroesophageal reflux 2 months prior to admission. After 5 weeks of therapy, she stopped taking pantoprazole due to general malaise. Upon admission, all home medications, including pantoprazole, were reinitiated based on the patient's medication list. Serum creatinine increased to 6.1 mg/dL on day 4 of admission from a baseline of 1.0 mg/dL. Pantoprazole therapy was promptly discontinued, and prednisone 40 mg/d was initiated. Urinalysis revealed eosinophils, and a subsequent renal biopsy confirmed a diagnosis of AIN. The serum creatinine level gradually declined over 2 weeks, and the patient was discharged home with a serum creatinine level of 1.6 mg/dL. The Naranjo probability scale suggests a highly probable relationship between AIN and pantoprazole therapy in this patient. DISCUSSION: Drug hypersensitivity reactions are the most common cause of AIN. There have been several reported cases of omeprazole-induced AIN. Although there are very few prospective data on the efficacy of treatment of drug-induced AIN, corticosteroids may have a role in recovery of renal function. Prednisone doses of 1 mg/kg/d have been suggested. CONCLUSIONS: Physicians should be aware that drug-induced AIN can be associated with proton-pump inhibitors. Early detection of this rare adverse reaction may prevent acute renal insufficiency.     

A randomized trial of two weight-based doses of insulin glargine and glulisine in hospitalized subjects with type 2 diabetes and renal insufficiency

OBJECTIVE Renal insufficiency may increase the risk of hypoglycemia in hospitalized patients with diabetes who are treated with insulin. We randomized inpatients with type 2 diabetes and chronic renal failure to treatment with two different dose levels of insulin glargine and glulisine and studied control of hyperglycemia and the frequency of hypoglycemia. RESEARCH DESIGN AND METHODS We conducted a multicenter, prospective, randomized trial to compare the efficacy of once-daily glargine and three-times daily glulisine at 0.5 vs. 0.25 units/kg/day. A total of 107 subjects had type 2 diabetes for >1 year, had a glomerular filtration rate <45 mL/min but did not require dialysis, and had an initial blood glucose (BG) >180 mg/dL. Doses were adjusted based on four-times daily BG measurements for 6 days. RESULTS Mean BG on the first day was 196 ± 71 mg/dL in the group receiving 0.5 units/kg (0.5 group) and 197 ± 55 mg/dL in the group receiving 0.25 units/kg (0.25 group; P = 0.94). On days 2 to 6, mean BG was 174 ± 52 mg/dL in the 0.5 group and 174 ± 46 mg/dL in the 0.25 group (P = 0.96). There were no significant differences between groups in the percentage of BG values within the target range of 100 to 180 mg/dL on any of the 6 study days. In the 0.5 group, 30% experienced hypoglycemia (BG <70 mg/dL) compared with 15.8% of the 0.25 group (P = 0.08). CONCLUSIONS Reduction of initial glargine/glulisine insulin weight-based dosing in hospitalized patients with diabetes and renal insufficiency reduced the frequency of hypoglycemia by 50% without compromising the control of hyperglycemia.     

Impact of a subcutaneous insulin protocol in the emergency department: Rush Emergency Department Hyperglycemia Intervention (REDHI)

Objective: We evaluated a hyperglycemia treatment protocol for use in the Emergency Department (ED) in patients with diabetes mellitus (DM) before admission to the hospital or discharge home. Methods: Fifty-four consecutive patients with a history of DM and an ED admission blood glucose (BG) > 200 mg/dL were treated with subcutaneous (SQ) insulin aspart every 2 h until BG was < 200 mg/dL. Point-of-care BG was measured immediately on ED admission and every 2 h until discharge home or hospital admission. The intervention group was compared with 54 historical controls with DM and an ED admission BG > 200 mg/dL. Results: One hundred percent of intervention patients received insulin aspart, whereas only 35% of historical controls received insulin therapy. In the intervention group, mean BG declined from 333 ± 104 mg/dL on ED admission to 158 ± 68 mg/dL on ED discharge. In the historical control group, mean BG decline was significantly less, from 322 ± 126 mg/dL on admission to 242 ± 79 mg/dL on discharge (p < 0.001). Sixty-nine percent of intervention patients and 67% of controls were subsequently admitted to the hospital. Mean hospital length of stay (LOS) in the intervention group was significantly less, 3.8 ± 3.3 days, compared with 5.3 ± 4.1 days in the control group (p < 0.05). Four intervention patients (7.4%) developed a BG < 70 mg/dL. Conclusion: A protocol for the treatment of acute hyperglycemia in the ED can be safely implemented. Subsequent inpatient LOS was reduced. Further randomized clinical trials of this intervention are warranted.     

A probable case of gabapentin-related reversible hearing loss in a patient with acute renal failure

BACKGROUND: As described in the literature, gabapentin toxicity in patients with impaired renal function can manifest as coma, myoclonus, tremulousness, or altered mental status. Gabapentin is an antiepileptic agent indicated for use as an adjunct therapy in partial seizures and postherpetic neuralgia but is also prescribed for the treatment of diabetic peripheral neuropathy. CASE SUMMARY: A 46-year-old white woman (height, 167 cm; weight, 177 kg; body mass index, 62.8 kg/m2) with a 6-year history of diabetes mellitus and previously normal renal function, presented to the emergency department of Wake Forest University Baptist Medical Center with anuria (a serum creatinine level of 7.4 mg/dL), hearing loss, myoclonus, and confusion with hallucinations lasting for 3 days. Her blood pressure was 110/74 mm Hg. The patient's preadmit medication list included: lisinopril (40 mg QD), hydrochlorothiazide (25 mg QD), and furosemide (80 mg QD) for hypertension; atorvastatin (10 mg QD) for hyperlipidemia; omeprazole (20 mg QD) for gastroesophageal reflux disease; salmeterol/fluticasone inhaler (100/50 microg; 1 puff BID) and albuterol metered-dose inhaler (90 microg as needed) for asthma; metformin (500 mg BID) and insulin lispro per sliding scale for type 2 diabetes mellitus; oxycodone controlled release (60 mg TID) for chronic osteoarthritis and low back pain; alprazolam (0.5 mg every 8 hours as needed) for generalized anxiety disorder; venlafaxine (150 mg BID) for depression; and gabapentin (300 mg TID) for diabetic peripheral neuropathy. The patient's symptoms (hearing loss, myoclonus, and confusion) improved after 1 session of hemodialysis (approximately 10 hours following admission) and had resolved at the time of discharge (4 days later). On admission, the gabapentin concentration was 17.6 microg/mL, and following hemodialysis, the gabapentin concentration was undetectable (by discharge/day 4). The timing of the patient's last dose of gabapentin is unknown. Normal doses for the treatment of diabetic peripheral neuropathy range from 900 to 3600 mg/d divided 3 times daily. Conclusions: We report a patient with acute renal failure who developed hearing loss, myoclonus, and confusion with hallucinations in the presence of elevated gabapentin concentrations. Due to rapid improvement after hemodialysis and discontinuation of gabapentin, we believe that these symptoms were probably due to gabapentin toxicity.     

Gatifloxacin and the elderly: pharmacokinetic-pharmacodynamic rationale for a potential age-related dose reduction

OBJECTIVES: Recently, anecdotal reports via the FDA's MedWatch reporting system have documented rare but serious hyperglycaemia in elderly patients receiving gatifloxacin. One possible factor contributing to these events may be gatifloxacin overexposure, resulting from age-related decreases in renal function in elderly patients predisposed to glycaemic alterations. These analyses examine gatifloxacin exposure in 10 patients with severe hyperglycaemia, provide a pharmacokinetic-pharmacodynamic (PK-PD) rationale for a potential age-related dose reduction to avoid high exposures, and evaluate the likely impact of such a dose reduction on clinical efficacy in this specific patient population. METHODS: First, a previously derived population pharmacokinetic model, with patient demographics, was used to estimate gatifloxacin AUC0-24 following a dosage regimen of 400 mg/24 h in 10 index patients with severe hyperglycaemia. Second, the population pharmacokinetic model and patient demographic data from 2696 patients aged > or =65 years from two New Drug Application (NDA) databases were used to estimate AUC0-24 following dosage regimens for gatifloxacin of 200 and 400 mg/24 h. Finally, Monte Carlo simulation was utilized to assess the probability of achieving PK-PD target exposures against Streptococcus pneumoniae in elderly patients using these regimens. RESULTS: The mean estimated AUC0-24 among severe hyperglycaemia cases was 74 mg.h/L (range 57-100). Gatifloxacin AUC0-24 exposures for the 400 mg regimen were predicted to be higher in patients aged > or =65 years and similar to the severe hyperglycaemia cases. The probability of AUC0-24 > or =60 and > or =70 in patients aged > or =65 years for the 200 mg regimen was 0.03 and <0.01, respectively, versus 0.51 and 0.35 for the 400 mg regimen, respectively. The probability of achieving PK-PD target exposures against S. pneumoniae in patients aged > or =65 years receiving the 200 mg regimen was 0.99. CONCLUSIONS: The probability of a patient aged > or =65 years having an AUC0-24 > or =60-70 mg.h/L is markedly lower following a 200 mg regimen relative to a 400 mg regimen, suggesting a decreased risk of severe hyperglycaemia in a predisposed patient. Moreover, a dose reduction does not appear to significantly modify the likelihood of achieving the PK-PD target of gatifloxacin against S. pneumoniae.     

Risk factors for hyperglycemia in hospitalized adults receiving gatifloxacin: a retrospective, nested case-controlled analysis

Background: The prevalence of glucose abnormalities has been reported to be greater in hospitalized patients receiving gatifloxacin than in patients receiving ceftriaxone. Objective: The purpose of the current study was to identify risk factors for hyperglycemia in hospitalized patients receiving gatifloxacin. Methods: This retrospective, nested case-controlled study was conducted in 69 patients and 69 controls in 2 nonteaching hospitals in Houston, Texas. Classification and regression tree (CART) analysis was conducted to identify break points in continuous variables. Univariate and multivariate logistic regression analyses were also performed. Results: A total of 138 patients (mean [SD] age, 68.3 [17.3] years; weight, 77.4 [21.1] kg; sex, women/ men, 69.6%/30.4%; race [Hispanic, 58.3%; white, 28.5%; black, 9.2%; other, 4.0%]) were identified. Patients who developed hyperglycemia (blood glucose level >200 mg/dL) within 72 hours of gatifloxacin ad-ministration (cases) were matched 1:1 with patients who received gatifloxacin for >/=5 days and did not experience hyperglycemia during treatment and for 3 days after the end of treatment (controls). In univariate analysis, cases were more likely than controls to have diabetes (89.9% vs 13.0%; P < 0.001), have a decreased mean (SD) creatinine clearance (CrCl) (53.8 [36.8] vs 69.2 [45.3] mL/min; P = 0.025), be located in the intensive care unit at the time of the event (20.3% vs 7.2%; P = 0.02), have received gatifloxa-cin doses higher than recommended based on renal function (>200 mg/d when CrCl <40 mL/min) (25/69 [36.2%] vs 9/69 [13.0%]), have leukocytosis (mean [SD] white blood cell [WBC] count, 15.5 [7.4] vs 12.8 [6.2] cells/mm3), and have received concomitant total parenteral nutrition (7/69 [10.1%] vs 0 [0%]; P = 0.02) and/or steroids (22/69 [31.9%] vs 8/69 [11.6%]; P = 0.008). CART analysis identified age >65 years, albumin <3.2 g/dL, WBC count >14.5 cells/mm3, and CrCl <40 mL/min to be more common in hyperglycemic patients. In logistic regression, diabetes (odds ratio [OR] = 233; 95% CI, 19-2784) and excessive dose for renal function (OR = 42; 95% CI, 2-770) were identified as independent predictors for hyperglycemia in patients receiving gatifloxacin. After controlling for diabetes, concomitant steroids (OR = 5.7; 95% CI, 1.5-21.1) and excessive dose for renal function (OR = 4.9; 95% CI, 1.2-20.4) were associated with hyperglycemia in patients receiving gatifloxacin. Conclusions: This retrospective, nested case-controlled study found that the risk of hyperglycemia increased in diabetic patients who received concomitant steroids or higher gatifloxacin doses than recommended by the manufacturer's prescribing information. The application of these data should be assessed for other fluoroquinolones used at higher doses.     

Hyperglycemia and mortality in elderly patients with Staphylococcus aureus bacteremia

OBJECTIVE: To investigate the association between hyperglycemia and in-hospital mortality in elderly patients with Staphylococcus aureus bacteremia (SAB). METHODS: We reviewed the medical records of 135 elderly patients with SAB admitted to two tertiary medical centers from January 2003 until December 2004. Patients were stratified into two groups: those with a 7-day post-SAB mean blood glucose < 170 mg/dL and those with a 7-day post-SAB mean blood glucose > or = 170 mg/dL. A stepwise logistic regression analysis was performed to determine whether the degree of hyperglycemia was a significant predictor of mortality. RESULTS: Seventy-four (54.8%) patients had methicillin-resistant Staphylococcus aureus bacteremia. During the follow-up period from admission until discharge, 36 (26.7%) patients died. Twenty-one (21.4%) of 98 patients with a 7-day post-SAB mean blood glucose < 170 mg/dL died, while 15 (40.5%) of 37 patients with a 7-day post-SAB mean blood glucose > or = 170 mg/dL expired. Multivariate analysis identified 3 independent determinants of death: Simplified Acute Physiology Score (SAPS) score at onset of SAB > 45 (OR 5.3, 95% CI {1.8, 15.5}, P = 0.002), a 7-day post-SAB mean blood glucose > or = 170 mg/dL (OR 3.3, 95% CI {1.2, 9.2}, P = 0.03), and altered mental status at the onset of SAB (OR 7.8, 95% CI {2.5, 23.9}, P = 0.0003). CONCLUSIONS: Hyperglycemia is an important marker of increased mortality among hospitalized elderly patients with SAB.     

Propylene glycol-induced lactic acidosis in a patient with normal renal function: a proposed mechanism and monitoring recommendations

OBJECTIVE: To report a case of severe propylene glycol-induced lactic acidosis not attributable to renal dysfunction that was secondary to administration of high-dose intravenous lorazepam. CASE SUMMARY: A 24-year-old female with community-acquired pneumonia presented with severe acute respiratory distress syndrome. To maintain adequate sedation and ventilation and reduce airway pressure, several relaxation strategies were used including high-dose intravenous lorazepam, fentanyl, and cisatracurium. After 18 days of high-dose continuous infusion of lorazepam (maximum dose 50 mg/h), the patient developed severe lactic acidosis secondary to propylene glycol toxicity, the main diluent of lorazepam. The acidosis temporarily resolved with bicarbonate administration and discontinuation of lorazepam. Her renal function remained stable for a time (serum creatinine 0.5 mg/dL, blood urea nitrogen 10 mg/dL, urine output 100-200 mL/h). However, after several more days, the patient's condition deteriorated, and she ultimately died. DISCUSSION: Previous cases of propylene glycol toxicity secondary to high-dose lorazepam infusion have occurred in patients with compromised renal function. Our patient's renal function remained stable throughout the hospital course, which caused us to look further for an explanation for the propylene glycol-induced lactic acidosis. Based on the Naranjo probability scale, propylene glycol was determined to be the probable cause of lactic acidosis. Since this case occurred, our intensive care unit has instituted recommendations for the prevention of lorazepam-associated propylene glycol toxicity. CONCLUSIONS: Our case highlights the development of propylene glycol-induced lactic acidosis secondary to high-dose lorazepam infusion not associated with renal dysfunction.     

Enoxaparin-induced retroperitoneal hematoma

OBJECTIVE: To report 2 cases of retroperitoneal hematoma in elderly patients receiving enoxaparin. CASE SUMMARIES: Two white men, aged 70 and 71 years, received enoxaparin 80 mg subcutaneously twice a day for 8 and 4 days, respectively. Baseline hemoglobin and hematocrit values were 9.5 g/dL and 28.9% and 11.2 g/dL and 32.8%, respectively. In both cases, after the hemoglobin and hematocrit values decreased to 6.6 g/dL and 20.4% and 5.1 g/dL and 15.2%, respectively, a computed tomography scan revealed a retroperitoneal hematoma. DISCUSSION: Enoxaparin is a frequently used anticoagulant. Major bleeding episodes are reported to occur at a rate of up to 5.2%. Factors that increase the risk of bleeding in patients receiving enoxaparin are the use of high doses of enoxaparin, advanced age, renal impairment, and the concomitant use of drugs affecting hemostasis. Both of these patients received relatively high doses of 0.80 and 0.94 mg/kg subcutaneously twice a day, were elderly, and had mild renal impairment; 1 received aspirin concomitantly, while the other received aspirin 4 days prior and warfarin 1 day prior to bleeding. CONCLUSIONS: There are very few published reports implicating enoxaparin as a factor in retroperitoneal hematoma. It is hoped that the addition of these 2 cases to the medical literature creates more awareness that retroperitoneal hematoma should be considered in the differential diagnosis in patients receiving enoxaparin and experiencing unexplained decreases in hemoglobin and hematocrit.     

High-dose methylprednisolone therapy in pure red cell aplasia

OBJECTIVE: To report our experience using high-dose methylprednisolone (HDMP) treatment in a patient with primary acquired pure red cell aplasia (PRCA) who failed to respond to conventional prednisone therapy. CASE SUMMARY: A 29-year-old woman reported weakness, was easily fatigued, and had developed palpitations. On physical examination, pallor and splenomegaly were detected. On blood smear, mild macrocytic anemia was seen. Bone marrow aspiration and biopsy revealed normocellularity, erythroid hypoplasia (E/M: 1/10), reduction in erythroid precursors, and normal megakaryocytes and myeloid series. No disease associated with secondary PRCA was detected. Oral prednisone 1 mg/kg (total 60 mg/d) was started as conventional treatment. However, the patient's status deteriorated and the hemoglobin concentration fell from 6.5 to 5.5 g/dL within the first week of hospitalization. HDMP was then begun. Treatment protocol consisted of methylprednisolone 30 mg/kg for 4 days, 20 mg/kg for 3 days, 10 mg/kg for 3 days, 5 mg/kg for 4 days, and 1 mg/kg for 2 weeks. The patient's hemoglobin concentration increased from 5.5 to 14.2 g/dL over a period of 9 weeks. Transient hyperglycemia and cushingoid appearance were seen during prednisone treatment. DISCUSSION: Exactly how steroids enhance erythropoiesis in PRCA is unknown. It seems likely that steroids render abnormal erythroid progenitors more sensitive to marrow growth factors, thereby permitting them to differentiate to functional precursors. HDMP treatment had been rarely used in patients with primary acquired PRCA. Limited studies using HDMP have shown variable results. CONCLUSIONS: HDMP treatment may be considered safe and effective in patients with primary acquired PRCA who do not respond to conventional steroid therapy.     

Psychiatric disturbances associated with ganciclovir therapy.

OBJECTIVE: To report a case of possible ganciclovir-induced psychiatric disturbances. CASE SUMMARY: A patient with AIDS who had no known psychiatric history and mild renal dysfunction experienced exacerbation of cytomegalovirus retinitis and was treated with ganciclovir 5 mg/kg iv q12h. The patient complained of nightmares and developed visual hallucinations and severe agitation on day 15 of ganciclovir therapy. The problems resolved after haloperidol administration and ganciclovir withdrawal and reappeared when the same regimen was reinstituted. However, the patient was able to tolerate the maintenance dose of ganciclovir at 5 mg/kg/d along with haloperidol later without further episodes of visual hallucinations. DISCUSSION: Case reports in the literature on ganciclovir-or its analog, acyclovir-, induced psychiatric disturbances were reviewed and compared. The potential relationship between ganciclovir accumulation in patients with renal insufficiency and the observed central nervous system problems in our patient was postulated. CONCLUSIONS: It is likely that ganciclovir accumulation contributed to the acute psychotic episodes observed in our patient. Adjusting ganciclovir dosage based on the patient's renal function is probably the only approach required to prevent or reduce the incidence of these episodes.     

Bortezomib-dexamethasone combination in a patient with refractory multiple myeloma and impaired renal function

BACKGROUND: Multiple myeloma (MM) is a hematologic neoplasia characterized by the monoclonal proliferation of bone marrow plasma cells. Renal failure occurs in 20% to 30% of MM patients at diagnosis and in >50% with an advanced form of the disease. For those with advanced MM, often a high-risk group of patients with poor prognosis, salvage treatment for renal failure needs to avoid nephrotoxic drugs. CASE SUMMARY: We report a case of a 78-year-old white male (weight, 90 kg) presented to the Department of Medical Oncology and Hematology, Istituto Clinico Humanitas, Rozzano, Milan, Italy, with refractory MM immunoglobulin G kappa (IgGkappa), Durie-Salmon Stage IIA, with progressive renal failure after an oral melphalan, prednisone, and thalidomide regimen (4 mg/m2.d, 40 mg/m2.d for 7 days every 6 weeks, and 100 mg/d, respectively). The patient had documented increments of serum monoclonal component (M-protein), anemia, and renal failure with Bence Jones proteinuria (serum creatinine, 2.9 mg/dL; creatinine clearance, 30 mL/min; hemoglobin, 10.9 g/dL; serum IgGkappa M-protein, 3.9 g/dL; proteinuria 3.5 g/d;light-chain level in urine, 1.2 g/L). After 2 cycles with bortezomib at a reduced dose (1.0 mg/m2 twice weekly for 2 weeks followed by a 10-day rest period) to evaluate tolerability and renal toxicity, the patient completed another 3 cycles at the standard dose (1.3 mg/m2) in combination with dexamethasone (20 mg on the day of bortezomib administration and the day after). This led to an improvement of the renal function with a reduction of serum and urinary M-protein (serum creatinine 1.4 mg/dL; serum IgGkappa M-protein, 2.9 g/dL; proteinuria, 2 g/d; kappa light-chain level in urine, 0.7 g/L). The patient developed thrombocytopenia but did not suffer from some of the more severe adverse events associated with bortezomib, such as infection or peripheral neuropathy, even at full dose. CONCLUSION: We report an elderly patient with refractory MM and progression with renal failure who responded to bortezomib treatment. Bortezomib was well tolerated in this patient.     

Possible valacyclovir-related neurotoxicity and aseptic meningitis

OBJECTIVE: To report a case of neurotoxicity and aseptic meningitis in a patient receiving valacyclovir.CASE SUMMARY: An 86-year-old white man had started valacyclovir 1 g 3 times a day for a herpetic rash along the left side of his face. He subsequently presented with balance difficulties, constant frontal headaches, and a seizure 1 day prior to admission. Cerebral spinal fluid (CSF) analysis revealed 162 white cells/mm(3), 1 red blood cell/mm(3), glucose 56 mg/dL, and protein 144 mg/dL, with a negative Gram stain. Further laboratory examination failed to demonstrate other causes for the patient's clinical picture. After discontinuation of valacyclovir and supportive care, the patient symptomatically improved.DISCUSSION: As of the third week of September 2003, only 1 other case of valacyclovir-related aseptic meningitis was published describing a patient with characteristics similar to those of our patient. Our patient's neurologic symptoms may have been due to acyclovir toxicity, but acyclovir-toxic patients present with normal CSF findings. Several drug classes, including nonsteroidal antiinflammatory drugs, antibiotics, and intravenous immunoglobulins, can induce aseptic meningitis. Other reasons for the patient's symptoms or causes of meningitis were excluded, although viral meningitis remains a possibility. Valacyclovir-induced aseptic meningitis was considered to be possible according to the Naranjo probability scale.CONCLUSIONS: Healthcare providers should be aware of valacyclovir as a possible cause of drug-induced aseptic meningitis.     

Probable levetiracetam-associated depression in the elderly: Two case reports

Background: Compared with traditional antiepileptic drugs, levetiracetam has a unique mechanism of action and unique properties, including predominant renal excretion and lack of drug-drug interactions. In the elderly, depression associated with levetiracetam has not been reported.Case summaries: A 73-year-old black man (height, 172.7 cm; weight, 92.7 kg; body mass index [BMI], 31 kg/m²) with stage 4 kidney disease was taking levetiracetam 500 mg BID for partial complex seizures. After 5 months of taking medication, new-onset depression, evidenced by depressed mood, weight loss, fatigue, and appearing withdrawn, was noted in this patient. Levetiracetam was discontinued by order of the patient's primary care physician. At a follow-up appointment 4 weeks later, the depressive symptoms had nearly resolved. The patient's Naranjo Adverse Drug Reaction Probability Scale score was 6, indicating levetiracetam to be a probable cause of depression in this patient. In a second case, a 92-year-old white woman (height, 154.9 cm; weight, 54.5 kg; BMI, 22.7 kg/m²) with existing chronic kidney disease and new-onset partial seizure, likely due to a meningioma, was initiated on levetiracetam 500 mg once daily. Depressive symptoms (eg, anhedonia, hypersomnolence, decreased appetite) were noted within 5 weeks. Cessation led to improvement in mood and cognition within 8 days. Based on this patient's Naranjo Adverse Drug Reaction Probability Scale score of 6, levetiracetam was a probable cause of depression in this patient.Conclusions: Levetiracetam was a probable cause of depression in these 2 elderly patients. Cautious use and additional monitoring may be necessary when prescribing levetiracetam to elderly patients, especially when prescribing to those with a history of renal impairment.     

Admission Blood Glucose Level and Its Association With Cardiovascular and Renal Complications in Patients Hospitalized With COVID-19

OBJECTIVETo investigate the association between admission blood glucose levels and risk of in-hospital cardiovascular and renal complications.RESEARCH DESIGN AND METHODSIn this multicenter prospective study of 36,269 adults hospitalized with COVID-19 between 6 February 2020 and 16 March 2021 (N = 143,266), logistic regression models were used to explore associations between admission glucose level (mmol/L and mg/dL) and odds of in-hospital complications, including heart failure, arrhythmia, cardiac ischemia, cardiac arrest, coagulation complications, stroke, and renal injury. Nonlinearity was investigated using restricted cubic splines. Interaction models explored whether associations between glucose levels and complications were modified by clinically relevant factors.RESULTSCardiovascular and renal complications occurred in 10,421 (28.7%) patients; median admission glucose level was 6.7 mmol/L (interquartile range 5.8–8.7) (120.6 mg/dL [104.4–156.6]). While accounting for confounders, for all complications except cardiac ischemia and stroke, there was a nonlinear association between glucose and cardiovascular and renal complications. For example, odds of heart failure, arrhythmia, coagulation complications, and renal injury decreased to a nadir at 6.4 mmol/L (115 mg/dL), 4.9 mmol/L (88.2 mg/dL), 4.7 mmol/L (84.6 mg/dL), and 5.8 mmol/L (104.4 mg/dL), respectively, and increased thereafter until 26.0 mmol/L (468 mg/dL), 50.0 mmol/L (900 mg/dL), 8.5 mmol/L (153 mg/dL), and 32.4 mmol/L (583.2 mg/dL). Compared with 5 mmol/L (90 mg/dL), odds ratios at these glucose levels were 1.28 (95% CI 0.96, 1.69) for heart failure, 2.23 (1.03, 4.81) for arrhythmia, 1.59 (1.36, 1.86) for coagulation complications, and 2.42 (2.01, 2.92) for renal injury. For most complications, a modifying effect of age was observed, with higher odds of complications at higher glucose levels for patients age <69 years. Preexisting diabetes status had a similar modifying effect on odds of complications, but evidence was strongest for renal injury, cardiac ischemia, and any cardiovascular/renal complication.CONCLUSIONSIncreased odds of cardiovascular or renal complications were observed for admission glucose levels indicative of both hypo- and hyperglycemia. Admission glucose could be used as a marker for risk stratification of high-risk patients. Further research should evaluate interventions to optimize admission glucose on improving COVID-19 outcomes.