Divergent humoral responses to 23-valent pneumococcal polysaccharide vaccine in critically-ill burn and neurosurgical patients.

INTRODUCTION: Critically ill hospitalized patients are at increased risk of infection so we assessed the immunogenicity of 23-valent pneumococcal polysaccharide vaccine (PPSV23) administered within six days of injury. METHODS: This prospective observational study compared the immunogenicity of PPSV23 among critically ill burn and neurosurgical patients at a tertiary, academic medical center. Patients received PPSV23 vaccination within six days of ICU admission per standard of care. Consent was obtained to measure concentrations of vaccine-specific IgG to 14 of 23 serotype capsule-specific IgG in serum prior to and 14-35 days following PPSV23. A successful immunologic response was defined as both a ≥2-fold rise in capsule-specific IgG from baseline and concentrations of >1 mcg/mL to 10 of 14 measured vaccine serotypes. Immunologic response was compared between burn and neurosurgical patients. Multiple variable regression methods were used to explore associations of clinical and laboratory parameters to immunologic responses. RESULTS: Among the 16 burn and 27 neurosurgical patients enrolled, 87.5% and 40.7% generated a successful response to the vaccine, respectively (p = 0.004). Both median post-PPSV23 IgG concentrations (7.79 [4.56-18.1] versus 2.93 [1.49-8.01] mcg/mL; p = 0.006) and fold rises (10.66 [7.44-14.56] versus 3.48 [1.13-6.59]; p<0.001) were significantly greater in burn compared with neurosurgical patients. Presence of burn injury was directly and days from injury to immunization were inversely correlated with successful immunologic response (both p<0.03). Burn injury was associated with both increased median antibody levels post-PPSV23 and fold rise to 14 vaccine serotypes (p<0.03), whereas absolute lymphocyte count was inversely correlated with median antibody concentrations (p = 0.034). CONCLUSION: Critically ill burn patients can generate successful responses to PPSV23 during acute injury whereas responses among neurosurgical patients is comparatively blunted. Further study is needed to elucidate the mechanisms of differential antigen responsiveness in these populations, including the role of acute stress responses, as well as the durability of these antibody responses.

Hypersensitivity Reaction Following Administration of Low-Dose Oral Vancomycin for the Treatment of Clostridium difficile in a Patient With Normal Renal Function.

Systemic absorption of oral vancomycin for the treatment of Clostridium difficile is thought to be trivial in patients without risk factors for increased systemic absorption and is often overlooked in clinical practice. A 51-year-old male elicits a suspected immunoglobulin E-mediated hypersensitivity following administration of low-dose oral vancomycin for the treatment of severe C difficile. The patient had normal renal function and was administered low doses of the medication, however, had a medical history significant for diverticulitis. Applying the Naranjo adverse drug reaction probability scale, a score of 5 was obtained, indicating a probable association between the administration of oral vancomycin and the hypersensitivity reaction. This case demonstrates that hypersensitivity reactions following low-dose oral vancomycin administration in patients with severe C difficile are possible, despite having normal renal function. Other risk factors for systemic absorption of oral vancomycin need to be evaluated in the literature, including severity of disease and underlying gastrointestinal processes.

Thiocyanate Accumulation in Critically Ill Patients Receiving Nitroprusside Infusions.

PURPOSE: This study evaluated thiocyanate concentrations and factors associated with thiocyanate accumulation in intensive care unit patients receiving nitroprusside with and without sodium thiosulfate coadministration. MATERIALS AND METHODS: This retrospective study evaluated critically ill adults who received nitroprusside infusions and had at least one thiocyanate concentration. Patients with thiocyanate accumulation (concentrations ≥30 µg/mL) were compared to patients without accumulation. Factors associated with accumulation were determined by Spearman correlation and multivariate regression. RESULTS: Thiocyanate concentrations (n = 192) were obtained from 87 patients. Fourteen of the 87 (16%) patients experienced thiocyanate accumulation with a mean (SD) thiocyanate concentration of 44 ± 11 µg/mL. Patients with accumulation had received greater cumulative nitroprusside doses (28 vs 8.2 mg/kg, P < .01), greater cumulative sodium thiosulfate doses (16.8 vs 10.1 mg/kg, P < .01), and longer infusion durations (10.9 vs 6.0 days, P < .01), compared to patients without accumulation. Sodium thiosulfate coadministration resulted in greater thiocyanate concentrations (22.8 ± 16.7 vs 16.8 ± 14.9 µg/mL, P = .01), despite utilization of lower cumulative nitroprusside doses (10.2 vs 14.6 mg/kg, P = .03). Cumulative nitroprusside dose ( r2 .44, P < .001) and cumulative sodium thiosulfate dose ( r2 .32, P < .001) demonstrated a significant correlation with measured thiocyanate concentrations. Thiocyanate accumulation was independently associated with cumulative nitroprusside dose in mg/kg (regression coefficient 0.75, 95% CI 0.63-0.89; P < .01). No clinically significant adverse effects of cyanide or thiocyanate toxicity were observed. CONCLUSIONS: Cumulative nitroprusside dose was independently associated with thiocyanate accumulation. Despite elevated thiocyanate levels in 16% of patients, there was no clinical evidence of cyanide or thiocyanate toxicity. Routine monitoring of thiocyanate concentrations appears most warranted in patients receiving higher cumulative doses of nitroprusside.