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In 2016, the proportion of Neisseria gonorrhoeae isolates with reduced susceptibility to azithromycin rose to 3.6%. A phylogenetic analysis of 334 N. gonorrhoeae isolates collected in 2016 revealed a single, geographically diverse lineage of isolates with MICs of 2 to 16 μg/ml that carried a mosaic-like mtr locus, whereas the majority of isolates with MICs of ≥16 μg/ml appeared sporadically and carried 23S rRNA mutations. Continued molecular surveillance of N. gonorrhoeae isolates will identify new resistance mechanisms., (Copyright © 2020 American Society for Microbiology.)

Background: Given the lack of new antimicrobials or a vaccine, understanding the evolutionary dynamics of Neisseria gonorrhoeae is a significant public and global health priority. We investigated the emergence and spread of gonococcal strains with decreased susceptibility to cephalosporins and azithromycin using detailed genomic analyses of gonococcal isolates collected in the United States, 2014-2016., Methods: We sequenced genomes of 649 isolates collected through the Gonococcal Isolate Surveillance Project. We examined the genetic relatedness of isolates and assessed associations between clades and various genotypic and phenotypic combinations., Results: We identified a large and clonal lineage of strains (MLST ST9363) associated with elevated azithromycin minimum inhibitory concentration (AZIem), characterized by a mosaic mtr locus (C substitution in the mtrR promoter, mosaic mtrR and mtrD). Mutations in 23S rRNA were sporadically distributed among AZIem strains. Another clonal group (MLST ST1901) possessed 7 unique PBP2 patterns, and it shared common mutations in other genes associated with cephalosporin resistance., Conclusions: Whole-genome sequencing methods can enhance monitoring of antimicrobial resistant gonococcal strains by identifying gonococcal populations containing mutations of concern. These methods could inform the development of point-of-care diagnostic tests designed to determine the specific antibiotic susceptibility profile of a gonococcal infection in a patient., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Laboratory monitoring for adverse effects to isotretinoin occurs with variability. Standardization of laboratory monitoring practices represents an opportunity to improve quality of care., Objective: We sought to develop an evidence-based approach to laboratory monitoring of patients receiving isotretinoin therapy for acne., Methods: We reviewed laboratory data from 515 patients with acne undergoing 574 courses of isotretinoin from March 2003 to July 2011. Frequency, timing, and severity of abnormalities were determined., Results: Clinically insignificant leukopenia or thrombocytopenia occurred in 1.4% and 0.9% of patients, respectively. Elevated liver transaminases were detected infrequently and not significantly increased compared with baseline detection rates (1.9% vs 1.6% at baseline). Significant elevations occurred with triglyceride (19.3%) and cholesterol (22.8%) levels. The most severe abnormalities were grade 2 (moderate). Mean duration of treatment before abnormalities were detected was 56.3 days for hypertriglyceridemia, 61.9 days for alanine transaminitis, and 50.1 days for hypercholesterolemia., Limitations: This was a single-center experience examining variable isotretinoin laboratory monitoring practices., Conclusions: In healthy patients with normal baseline lipid panel and liver function test results, repeated studies should be performed after 2 months of isotretinoin therapy. If findings are normal, no further testing may be required. Routine complete blood cell count monitoring is not recommended., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

During an 18-month period in a pediatric intensive care unit, nine patients with vocal cord paralysis were identified using flexible bronchoscopy. When tracheally extubated, each child was found to have stridor. The children ranged in age from 17 days to 5 1/2 years. Two patients had unilateral paralysis, but neither required tracheostomy. Seven patients displayed bilateral abductor vocal cord paralysis. Of these, six patients required tracheostomy. Surgical injury to the recurrent laryngeal nerve was the probable cause in two patients. The other seven patients had neurologic disorders with documented or suspected increases of intracranial pressure. Four of the seven patients with bilateral abductor vocal cord paralysis regained cord mobility within 4 months. Both children with unilateral cord paralysis have no stridor and vocalize well 1 year later. Cord paralysis in the setting of intracranial hypertension probably results from compression or ischemia of the vagus nerve before it exits the skull. Early visualization of the larynx should be done in patients who become stridulous when extubated, especially those with prior thoracic procedures or with neurologic disorders associated with intracranial hypertension.

We studied the effect of increasing systemic oxygen delivery (DO2) by packed RBC (PRBC) transfusion on oxygen consumption (VO2) in children with hyperdynamic septic shock. After routine resuscitation with volume loading and pharmacologic support, patients were studied if they had significant derangements of oxygen transport variables defined as: baseline VO2 less than 180 ml/min.m2 and oxygen extraction (O2 extr) less than 24%. Eight studies were performed. PRBC transfusion increased DO2 from 636 +/- 167 to 828 +/- 266 ml/min.m2 (p less than .01) without increasing cardiac index (5.2 +/- 1.3 vs. 5.0 +/- 1.4 L/min.m2). VO2 increased from 112 +/- 36 to 157 +/- 60 ml/min.m2 (p less than .01) while O2 extr was unchanged (18 +/- 3% vs. 19 +/- 6%). Despite initial low O2 extr, VO2 can be increased in pediatric septic shock by a further increase in DO2. Since VO2 correlates with survival, one should consider enhancing DO2 further despite initial low O2 extr and high DO2. Effects on morbidity and mortality require further study.

The NCCOM3-R6 monitor continuously monitors cardiac output and five other cardiovascular variables from the thoracic electrical bioimpedance signal. We averaged data over 5-min intervals for 130 min in 100 control studies in 40 pediatric ICU patients, age 0.04 to 20.39 yr (median 1.39) and weighing 2.0 to 59.5 kg (median 8.8). For individual studies, 99% of the 5-min averages of cardiac output fell within +/- 44% of the baseline cardiac output for that study. Normal ranges were somewhat narrower for the other five variables. When we averaged data for 100 studies, 5-min interval observations for each variable did not deviate from baseline over a 2-h period (p greater than .70). With a sample size of 100 studies, we could detect a change in cardiac output of +/- 5% at the p less than .005 level with a power of 0.95. We conclude that with a sufficiently large sample size, studies employing the NCCOM3 can detect clinically significant cardiovascular changes due to pharmacologic or procedural stressors.

The axillary vein was evaluated as an alternative access site for central venous catheterization in critically ill infants and children. Children were placed in the Trendelenberg position (when possible) with arm abducted 100 to 130 degrees. The vein was entered parallel and inferior to the artery. Success rate for catheterization was 79% (41/52). Catheter diameter range was 3 to 8.5 F and catheter length range was 5 to 30.5 cm. Median patient weight was 7.0 kg (3.0 to 59 kg). Median age was 0.91 years (14 days to 9 years). All central lines ended in the subclavian, innominate, or superior vena cava. Median catheter duration was 8 days (2 to 22 days). A total of 338 patient catheter-days were studied. Central venous pressure was successfully monitored in five of five attempts. Complications with insertion (3.8% of attempts) included one pneumothorax and one hematoma. Complications during catheter duration (9.8% of catheters, 1.1% per catheter-day) included one instance each of venous stasis, venous thrombosis, catheter sepsis, and parenteral nutrition infiltration. No complication contributed to a patient mortality. Success and complication rates were comparable with those in jugular catheterization studies in children. The axillary approach is an acceptable route for central venous catheterization in critically ill infants and children.

Mechanically ventilated children usually require a combination of sedation (morphine = M, diazepam = D) and paralysis (pancuronium = P) to minimize anxiety, discomfort, and the risks of self-extubation, tracheal injury, and pulmonary barotrauma. We sought to determine whether our use of MDP varied with patient age. Cases where the dosage of MDP would be influenced by neurological, hemodynamic, or painful diagnoses were excluded. The 36 cases selected were divided according to age into three groups (less than 4 months = A, 4-18 months = B, greater than 18 months = C). The daily sum of MDP dosages was calculated for each of the 326 study days, a mean of 9 study days for each case. The median daily drug usage in group B (2.3 mg/kg/day) was twice that in either group A (younger) or group C (older) (both p less than 0.001). This finding may be explained by developmental changes in physiology, pharmacology, and behavior, and may have been influenced by a paradoxical drug effect or multiple drug antagonism.

A randomized crossover protocol was used to compare conventional mechanical ventilation (CMV) and high-frequency ventilation (HFV) in mongrel dogs experiencing right ventricular dysfunction after right ventriculotomy. When inspired oxygen, pH, PCO2, core temperature, and preload were held constant, cardiac output increased significantly (p less than .05) from 1.16 +/- 0.24 to 1.38 +/- 0.25 L/min and pulmonary vascular resistance decreased significantly (p less than .05) from 734 +/- 257 to 554 +/- 169 dyne X sec/cm5 during HFV relative to CMV. We also noted a significant (p less than .05) increase in mean arterial pressure from 116 +/- 27 to 124 +/- 23 mm Hg and a significant (p less than .05) increase in left ventricular stroke work from 10.2 +/- 3.5 to 12.3 +/- 2.6 g X m during HFV. During the inspiratory phase of CMV there were increases in CVP, pulmonary artery pressure, and systemic arterial pressure, and decreases in pulmonary artery flow which did not occur during HFV. HFV may be preferable to CMV in the presence of right ventricular dysfunction.