Antibiotic Use and Respiratory Pathogens in Adults With Sickle Cell Disease and Acute Chest Syndrome.

Background: Acute chest syndrome (ACS) is an acute complication of sickle cell disease (SCD). Historically, the most common pathogens were Chlamydophila pneumoniae, Mycoplasma pneumoniae, and respiratory syncytial virus. Pediatric patients receiving guideline-adherent therapy experienced fewer ACS-related and all-cause 30-day readmissions compared with those receiving nonadherent therapy. This has not been evaluated in adults. Objectives: The primary objectives were to characterize antibiotic use and pathogens. The secondary objective was to assess the occurrence of readmissions associated with guideline-adherent and clinically appropriate treatment compared with regimens that did not meet those criteria. Methods: A retrospective cohort analysis was conducted for adults with SCD hospitalized between August 1, 2014, and July 31, 2017, with pneumonia (PNA) or ACS. The study was approved by the institutional review board. Results: A total of 139 patients with 255 hospitalizations were reviewed. Among 41 respiratory cultures, 3 organisms were isolated: Cryptococcus neoformans, Pseudomonas aeruginosa, and budding yeast. Respiratory panels were collected on 121 admissions, with 17 positive for 1 virus; all were negative for Chlamydophila pneumoniae and M pneumoniae. There were significantly more ACS-/PNA-related 7-day readmissions from patients on guideline-adherent regimens compared with nonadherent regimens (3.7% vs 0%; P = 0.04). Conclusion and Relevance: These findings challenge existing knowledge regarding the most common pathogens in adults with SCD with ACS or PNA. Routine inclusion of a macrolide may not be necessary. Future studies focused on pathogen characterization with standardized assessment are necessary to determine appropriate empirical therapy in this population.

Hepatorenal Acute Kidney Injury and the Importance of Raising Mean Arterial Pressure.

BACKGROUND: The efficacy of vasoconstrictors in hepatorenal syndrome (HRS) is variable. We hypothesized that the effectiveness of vasoconstrictor therapy in improving kidney function ultimately relates to the magnitude of the achieved mean arterial pressure (MAP) increase. METHODS: A retrospective study was conducted to identify cirrhotic individuals treated with vasoconstrictors for acute kidney injury (AKI) presumably caused by HRS to examine the relationship between change in MAP and change in serum creatinine (sCr) using multivariate mixed linear regression. RESULTS: Among 73 patients treated with midodrine/octreotide, change in MAP inversely correlated with change in sCr (p = 0.0005). The quartile with the greatest increase in MAP (+15.9 to +29.4 mm Hg) was associated with a subsequent absolute decrease in sCr. The strength of the correlation increased when the analysis was restricted to those who met the HRS criteria (n = 27, p = 0.002), where the third (+5.3 to +15.6 mm Hg) and fourth (+15.9 to +20.9 mm Hg) quartiles of MAP change were associated with a decrease in sCr. A similar but stronger correlation was found among 14 patients treated with norepinephrine either after failing midodrine/octreotide (n = 10) or de novo (n = 4; p = 0.002), where a rise in MAP of +19.2 to 25 mm Hg was associated with a larger reduction in sCr. Associations remained significant after adjustment for baseline parameters. CONCLUSIONS: The magnitude of MAP rise during HRS therapy with midodrine/octreotide or norepinephrine correlated with a reduction in sCr concentration. Our results suggest that achieving a pre-specified target of MAP increase might improve renal outcomes in hepatorenal AKI.

Intravenous conivaptan for the treatment of hyponatraemia caused by the syndrome of inappropriate secretion of antidiuretic hormone in hospitalized patients: a single-centre experience.

BACKGROUND: Intravenous conivaptan is a novel therapeutic agent indicated for the treatment of euvolaemic and hypervolaemic hyponatraemia. However, there is paucity of reported clinical experience using conivaptan for the treatment of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Moreover, while there is reasonable concern for overcorrection, no pre-treatment variables are known to be helpful to identify patients at risk for rapid correction. METHODS: We searched our records for hospitalized patients treated with intravenous conivaptan for moderate to severe hyponatraemia due to SIADH, with a starting serum sodium <130 mmol/L, between 2006 and 2009 (n = 18), to examine its efficacy as aquaretic, and to search for pre-treatment variables that could predict degree of response. RESULTS: Twenty-four hours after initiation of therapy, all patients had at least a 3-mmol/L increase in serum sodium, with 66.7% (12/18) of the patients having an absolute increase >or=4 mmol/L, and a median increase in serum sodium of 7 mmol/L (range: 3-16 mmol/L). Concomitantly, urine osmolality decreased in all patients with a mean reduction of 45.9 +/- 28.8% from baseline. Lower serum sodium, lower blood urea nitrogen and higher estimated glomerular filtration rate at baseline had a significant correlation with the magnitude of the absolute increase in serum sodium 24 hours after initiation of therapy. CONCLUSIONS: We conclude that intravenous conivaptan is an effective aquaretic to treat hyponatraemia caused by SIADH, as evidenced by a simultaneous increase in serum sodium and decrease in urine osmolality. Baseline values of serum sodium, blood urea nitrogen and estimated glomerular filtration rate may help predicting the magnitude of response to therapy.