Evolution of a laboratory mechanomyograph.

Mechanomyography is currently the accepted laboratory reference standard for quantitative neuromuscular blockade monitoring. Mechanomyographs are not commercially available. Previously, a mechanomyograph was built by our laboratory and used in several clinical studies. It was subsequently redesigned to improve its usability and functionality and to accommodate a wider range of hand sizes and shapes using an iterative design process. Each version of the redesigned device was initially tested for usability and functionality in the lab with the investigators as subjects without electrical stimulation. The redesigned devices were then assessed on patients undergoing elective surgery under general anesthesia without neuromuscular blocking drugs. Since the patients were not paralyzed, the expected train-of-four ratio was 1.0. The device accuracy and precision were represented by the train-of-four ratio mean and standard deviation. If issues with the device's useability or functionality were discovered, changes were made, and the redesign processes repeated. The final mechanomyograph design was used to collect 2,362 train-of-four ratios from 21 patients. The mean and standard deviation of the train-of-four ratios were 0.99 ± 0.030. Additionally, the final mechanomyograph design was easier to use and adjust than the original design and fit a wider range of hand sizes. The final design also reduced the frequency of adjustments and the time needed for adjustments, facilitating data collection during a surgical procedure.

Accuracy and Precision of Three Acceleromyographs, Three Electromyographs and a Mechanomyograph Measuring the Train-of-Four Ratio in the Absence of Neuromuscular Blocking Drugs.

BACKGROUND: The accuracy and precision of currently available, widely used acceleromyograph and electromyograph neuromuscular blockade monitors have not been well studied. In addition, the normalization of the train-of-four ratio from acceleromyography (train-of-four ratio [T4/T1] divided by the baseline train-of-four ratio) has not been validated in comparison to mechanomyography. METHODS: Enrolled patients had surgery under general anesthesia with a supraglottic airway and without any neuromuscular blocking drugs. Three acceleromyograph monitors, three electromyograph monitors and a mechanomyograph built in our laboratory were tested. Most patients had an electromyograph and the mechanomyograph on one arm and a third monitor on the contralateral arm. Train-of-four ratios were collected every 12-20 seconds for the duration of the anesthetic. At least 1,000 train-of-four ratios were recorded for each device. Gauge repeatability and reproducibility analysis was performed. RESULTS: Twenty-eight patients were enrolled. In total, 9,498 train-of-four ratio measurements were collected. Since no neuromuscular blocking drugs were used, the expected train-of-four ratio was 1.0. All of the acceleromyograph monitors produced overshoot in the train-of-four ratio (estimated means 1.10-1.13) and substantial variability (gauge standard deviations 0.07-0.18). Normalization of the train-of-four ratio measured by acceleromyography improved the estimated mean for each device (0.97-1.0) but the variability was not improved (gauge standard deviations 0.06-0.17). The electromyograph and the mechanomyograph monitors produced minimal overshoot (estimated means 0.99-1.01) and substantially less variation (gauge standard deviations 0.01-0.02). For electromyography and mechanomyography, 0.3% of all train-of-four ratios were outside of the range of 0.9-1.1. For acceleromyography, 27% to 51% of normalized train-of-four ratios were outside of the range of 0.9-1.1. CONCLUSION: Three currently available acceleromyograph monitors produced overshoot and substantial variability that could be clinically significant. Normalization corrected the overshoot in the average results but did not reduce the wide variability. Three electromyograph monitors measured the train-of-four ratio with minimal overshoot and variability, similar to a mechanomyograph.

A Dose-finding Study of Sugammadex for Reversal of Rocuronium in Cardiac Surgery Patients and Postoperative Monitoring for Recurrent Paralysis.

BACKGROUND: The dose of sugammadex recommended by the manufacturer for reversal of rocuronium is 2 mg/kg when the train-of-four count is 2 or more and 4 mg/kg when it is less than 2 but there is a posttetanic count of at least 1. The purpose of this dose-finding study was to titrate sugammadex to produce a train-of-four ratio 0.9 or greater at the conclusion of cardiac surgery, and to continue monitoring neuromuscular blockade in the intensive care unit to identify recurrent paralysis. The hypothesis was that many patients would require less than the recommended dose of sugammadex, but that some would require more, and that recurrent paralysis would not occur. METHODS: Neuromuscular blockade was monitored using electromyography during cardiac surgery. Administration of rocuronium was at the discretion of the anesthesia care team. During sternal closure, sugammadex was titrated in 50-mg increments every 5 min until a train-of-four ratio 0.9 or greater was obtained. Neuromuscular blockade was monitored with electromyography in the intensive care unit until sedation was discontinued before extubation or for a maximum of 7 h. RESULTS: Ninety-seven patients were evaluated. The dose of sugammadex required to achieve a train-of-four ratio of 0.9 or greater varied from 0.43 to 5.6 mg/kg. There was a statistically significant relationship between the depth of neuromuscular blockade and the sugammadex dose required for reversal, but there was a large variation in dose required at any depth of neuromuscular blockade. Eighty-four of 97 patients (87%) required less than the recommended dose, and 13 (13%) required more. Two patients required additional sugammadex administration for recurrent paralysis. CONCLUSIONS: When sugammadex was titrated to effect, the dose was usually less than the recommended dose, but it was more in some patients. Therefore, quantitative twitch monitoring is essential for ascertaining that adequate reversal has taken place after sugammadex administration. Recurrent paralysis was observed in two patients.

Comparison of a Modern Digital Mechanomyograph to a Mechanomyograph Utilizing an Archival Grass Force Transducer.

BACKGROUND: Mechanomyography is the traditional gold standard research technique for quantitative assessment of neuromuscular blockade. Mechanomyography directly measures the isometric force generated by the thumb in response to ulnar nerve stimulation. Researchers must construct their own mechanomyographs since commercial instruments are no longer available. A mechanomyograph was constructed, and its performance was compared against an archival mechanomyography system from the 1970s that utilized an FT-10 Grass force transducer, hypothesizing that train-of-four ratios recorded on each device would be equivalent. METHODS: A mechanomyograph was constructed using 3D-printed components and modern electronics. An archival mechanomyography system was assembled from original components, including an FT-10 Grass force transducer. Signal digitization for computerized data collection was utilized instead of the original paper strip chart recorder. Both devices were calibrated with standard weights to demonstrate linear voltage response curves. The mechanomyographs were affixed to opposite arms of patients undergoing surgery, and the train-of-four ratio was measured during the onset and recovery from rocuronium neuromuscular blockade. RESULTS: Calibration measurements exhibited a positive linear association between voltage output and calibration weights with a linear correlation coefficient of 1.00 for both mechanomyography devices. The new mechanomyograph had better precision and measurement sensitivity than the archival system: 5.3 mV versus 15.5 mV and 1.6 mV versus 5.7 mV, respectively (P < 0.001 for both). A total of 767 pairs of train-of-four ratio measurements obtained from eight patients had positive linear association (R 2 = 0.94; P < 0.001). Bland-Altman analysis resulted in bias of 3.8% and limits of agreement of -13% and 21%. CONCLUSIONS: The new mechanomyograph resulted in similar train-of-four ratio measurements compared to an archival mechanomyography system utilizing an FT-10 Grass force transducer. These results demonstrated continuity of gold standard measurement of neuromuscular blockade spanning nearly 50 yr, despite significant changes in the instrumentation technology.

The Association Between Hypophosphatemia and Lactic Acidosis After Cardiac Surgery With Cardiopulmonary Bypass: A Retrospective Cohort Study.

OBJECTIVES: The clinical significance of hypophosphatemia in cardiac surgery has not been investigated extensively. The aim of this study was to evaluate the association of postoperative hypophosphatemia and lactic acidosis in cardiac surgery patients at the time of intensive care unit (ICU) admission. DESIGN: A retrospective cohort study. SETTING: At a single academic center. PARTICIPANTS: Patients who underwent nontransplant cardiac surgery with cardiopulmonary bypass between August 2009 and December 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum phosphate and lactate levels were measured upon ICU admission in patients undergoing nontransplant cardiac surgery with cardiopulmonary bypass. There were 681 patients in the low-phosphate (<2.5 mg/dL) group and 2,579 patients in the normal phosphate group (2.5-4.5 mg/dL). A higher proportion of patients in the low phosphate group (26%; 179 of 681; 95% CI: 23-30) had severe lactic acidosis compared to patients in the normal phosphate group (16%; 417 of 2,579; 95% CI: 15-18). In an unadjusted logistic regression model, patients in the low phosphate group had 1.9-times the odds of having severe lactic acidosis (serum lactate ≥4.0 mmol/L) when compared to patients in the normal phosphate group (95% CI: 1.5-2.3), and still 1.4-times the odds (95% CI: 1.1-1.7) after adjusting for several possible confounders. CONCLUSIONS: Hypophosphatemia is associated with lactic acidosis in the immediate postoperative period in cardiac surgery patients. Future studies will need to investigate it as a potential treatment target for lactic acidosis.

Infection Prevention Precautions for Routine Anesthesia Care During the SARS-CoV-2 Pandemic.

Many health care systems around the world continue to struggle with large numbers of SARS-CoV-2-infected patients, while others have diminishing numbers of cases following an initial surge. There will most likely be significant oscillations in numbers of cases for the foreseeable future, based on the regional epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Less affected hospitals and facilities will attempt to progressively resume elective procedures and surgery. Ramping up elective care in hospitals that deliberately curtailed elective care to focus on SARS-CoV-2-infected patients will present unique and serious challenges. Among the challenges will be protecting patients and providers from recurrent outbreaks of disease while increasing procedure throughput. Anesthesia providers will inevitably be exposed to SARS-CoV-2 by patients who have not been diagnosed with infection. This is particularly concerning in consideration that aerosols produced during airway management may be infective. In this article, we recommend an approach to routine anesthesia care in the setting of persistent but variable prevalence of SARS-CoV-2 infection. We make specific recommendations for personal protective equipment and for the conduct of anesthesia procedures and workflow based on evidence and expert opinion. We propose practical, relatively inexpensive precautions that can be applied to all patients undergoing anesthesia. Because the SARS-CoV-2 virus is spread primarily by respiratory droplets and aerosols, effective masking of anesthesia providers is of paramount importance. Hospitals should follow the recommendations of the Centers for Disease Control and Prevention for universal masking of all providers and patients within their facilities. Anesthesia providers should perform anesthetic care in respirator masks (such as N-95 and FFP-2) whenever possible, even when the SARS-CoV-2 test status of patients is negative. Attempting to screen patients for infection with SARS-CoV-2, while valuable, is not a substitute for respiratory protection of providers, as false-negative tests are possible and infected persons can be asymptomatic or presymptomatic. Provision of adequate supplies of respirator masks and other respiratory protection equipment such as powered air purifying respirators (PAPRs) should be a high priority for health care facilities and for government agencies. Eye protection is also necessary because of the possibility of infection from virus coming into contact with the conjunctiva. Because SARS-CoV-2 persists on surfaces and may cause infection by contact with fomites, hand hygiene and surface cleaning are also of paramount importance.

Aviation-Style Computerized Surgical Safety Checklist Displayed on a Large Screen and Operated by the Anesthesia Provider Improves Checklist Performance.

BACKGROUND: Many hospitals have implemented surgical safety checklists based on the World Health Organization surgical safety checklist, which was associated with improved outcomes. However, the execution of the checklists is frequently incomplete. We reasoned that aviation-style computerized checklist displayed onto large, centrally located screen and operated by the anesthesia provider would improve the performance of surgical safety checklist. METHODS: We performed a prospective before and after observational study to evaluate the effect of a computerized surgical safety checklist system on checklist performance. We created checklist software and translated our 4-part surgical safety checklist from wall poster into an aviation-style computerized format displayed onto a large, centrally located screen and operated by the anesthesia provider. Direct observers recorded performance of the first part of the surgical safety checklist that was initiated before anesthetic induction, including completion of each checklist item, provider participation and distraction level, resistance to use of the checklist, and the time required for checklist completion before and after checklist system implementation. We compared trends of the proportions of cases with 100% surgical safety checklist completion over time between pre- and postintervention periods and assessed for a jump at the start of intervention using segmented logistic regression model while controlling for potential confounding variables. RESULTS: A total of 671 cases were observed before and 547 cases were observed after implementation of the computerized surgical safety checklist system. The proportion of cases in which all of the items of the surgical safety checklist were completed significantly increased from 2.1% to 86.3% after the computerized checklist system implementation (P < .001). Before computerized checklist system implementation, 488 of 671 (72.7%) cases had <75% of checklist items completed, whereas after a computerized checklist system implementation, only 3 of 547 (0.5%) cases had <75% of checklist items completed. CONCLUSIONS: The implementation of a computerized surgical safety checklist system resulted in an improvement in checklist performance.

The nociception level index (NOL) response to intubation and incision in patients undergoing video-assisted thoracoscopic surgery (VATS) with and without thoracic epidural analgesia. A pilot study.

Background: The PMD100™ (Medasense Biometrics Ltd., Ramat Yishai, Israel) is a novel non-invasive nociception monitor that integrates physiological parameters to compute a real-time nociception level index (NOL) in the anesthetized patients. Thoracic epidural analgesia provides effective analgesia and improves surgical outcomes. Side effects include sympathectomy, hypotension, changes in skin temperature and a decreased cardiac accelerator fiber tone. The purpose of this pilot study was to evaluate changes in NOL values after incision in patients with and without epidural analgesia.   Methods: Half of the patients scheduled for Video-Assisted Thoracoscopic Surgery (VATS) received a thoracic epidural catheter, placed and tested 2h before surgery and activated prior to incision. The other half of the patients received i.v. fentanyl (1 mcg/kg) five minutes before incision. Anesthesia and analgesia were maintained in a standardized manner. NOL and heart rate (HR) were compared before and after the nociceptive stimuli intubation and skin incision. Results: NOL significantly increased in all patients after intubation by 10.2 points (CI: 4.5-16.0; p=0.002) as well as HR by 9 beats per minute after intubation in all patients (CI: 3.3-15.6; p=0.01). After incision, in patients without epidural analgesia the NOL increased by 13.9 points (CI: 7.4-20.3; p=0.0001), compared to 5.4 points (CI: -6.3-17.1; p=0.29) in patients with epidural analgesia. HR did not significantly vary after incision in both groups. The area under the curve of delta NOL and delta HR variations after incision were significantly different (p<0.05) between groups and delta NOL variations were significantly different from baseline values but not the delta HR variations. Conclusions: This pilot study suggests that the PMD100™ Monitor may be a useful tool to evaluate the efficacy of an intraoperative thoracic epidural analgesia. Clinical Trial Registry Number: ClinicalTrials.gov record ID: NCT01978379 registered 10/25/2014.

Intravenous Acetaminophen as an Adjunct Analgesic in Cardiac Surgery Reduces Opioid Consumption But Not Opioid-Related Adverse Effects: A Randomized Controlled Trial.

OBJECTIVES: The authors hypothesized that intravenous acetaminophen as an adjunct analgesic would significantly decrease 24-hour postoperative opioid consumption. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: A single academic medical center. PARTICIPANTS: The study was comprised of 68 adult patients undergoing cardiac surgery. INTERVENTIONS: Patients were assigned randomly to receive either 1,000 mg of intravenous acetaminophen or placebo immediately after anesthesia induction, at the end of surgery, and then every 6 hours for the first 24 hours in the intensive care unit, for a total of 6-1,000 mg doses. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 24-hour postoperative opioid consumption. The secondary outcomes included 48-hour postoperative opioid consumption, incisional pain scores, opioid-related adverse effects, length of mechanical ventilation, length of intensive care unit stay, and the extent of wound hyperalgesia assessed at 24 and 48 hours postoperatively. The mean±standard deviation postoperative 24-hour opioid consumption expressed in morphine equivalents was significantly less in the acetaminophen group (45.6±29.5 mg) than in the placebo group (62.3±29.5 mg), representing a 27% reduction in opioid consumption (95% CI, 2.3-31.1 mg; p = 0.024). There were no differences in pain scores and opioid-related adverse effects between the 2 groups. A significantly greater number of patients in the acetaminophen group responded "very much" and "extremely well" when asked how their overall pain experience met their expectation (p = 0.038). CONCLUSIONS: The administration of intravenous acetaminophen during cardiac surgery and for the first 24 hours postoperatively reduced opioid consumption and improved patient satisfaction with their overall pain experience but did not reduce opioid side effects.

Ultrasound Identification of the Guidewire in the Brachiocephalic Vein for the Prevention of Inadvertent Arterial Catheterization During Internal Jugular Central Venous Catheter Placement.

BACKGROUND: Imaging the guidewire with ultrasonography in the internal jugular vein during central venous catheterization often is used to verify proper guidewire placement and to aid in prevention of inadvertent arterial catheterization. It is known, however, that inadvertent arterial catheterization can occur despite imaging the guidewire in the internal jugular vein because the guidewire may continue through the far wall of the internal jugular vein and into an adjacent artery. We propose confirmation of the guidewire in the brachiocephalic vein with ultrasonography as a more reliable method of confirming proper guidewire placement. METHODS: A prospective feasibility study of 200 adult cardiothoracic surgery patients undergoing internal jugular vein catheterization was performed to determine whether the guidewire could be imaged with ultrasonography in the brachiocephalic vein. The guidewire was imaged in the internal jugular vein in a short-axis view, and the transducer was then angled caudally under the clavicle, following the guidewire into the brachiocephalic vein. RESULTS: The right internal jugular vein was catheterized in 193 patients and the left internal jugular in 7 patients. The brachiocephalic vein was successfully imaged in all but 2 patients. In 3 patients, the guidewire could not be clearly identified in the brachiocephalic vein because of interference from the leads of a heart rhythm device (pacemaker or defibrillator) or preexisting catheter. In 2 patients, the guidewire was not seen initially in the brachiocephalic vein because of coiling in the internal jugular vein, and in 1 patient because of the guidewire passing into the right subclavian vein, but all 3 were subsequently imaged in the brachiocephalic vein after repositioning. CONCLUSIONS: During internal jugular vein catheterization, the brachiocephalic vein was imaged with ultrasonography in 99% of patients (the lower 1-sided 99% confidence limit is 96%). The guidewire was imaged in the brachiocephalic vein in all cases except when leads from a heart rhythm device caused interference, although in some patients with leads, the guidewire could be imaged without difficulty. The absence of the guidewire from the brachiocephalic vein was indicative of a malpositioned guidewire.

High-fidelity simulation of lung isolation with double-lumen endotracheal tubes and bronchial blockers in anesthesiology resident training.

OBJECTIVES: Demonstrate the feasibility of using the AirSim Bronchi airway simulator to teach residents how to manage lung isolation with double-lumen endotracheal tubes and bronchial blockers and evaluate their performance with a detailed checklist. DESIGN: Prospective observational study. SETTING: University anesthesiology residency training program. PARTICIPANTS: Anesthesiology residents taking a cardiothoracic anesthesiology rotation. INTERVENTIONS: Residents were instructed in 7 tasks using the AirSim Bronchi: The use of the fiberoptic bronchoscope, methods for placing left and right double-lumen endotracheal tubes and 3 bronchial blockers (Univent, Arndt, and Cohen), and application of continuous positive airway pressure (CPAP) to the unventilated lung. Two to 3 weeks later, checklists and a detailed scoring system were used to assess performance. Residents rated the curriculum and their own confidence in performing the tasks using a 5-point Likert scale. MEASUREMENTS AND MAIN RESULTS: Thirteen residents completed the curriculum. Their median Likert scale ratings of the curriculum based on a questionnaire with 6 items ranged from 4 to 5 of 5. Resident confidence scores for each lung isolation technique improved after the simulation training, with the median gain ranging from 0.5 to 1.5 Likert levels depending on the task. The largest improvement occurred with the bronchial blockers (p<0.05). The median performance score for the 7 tasks combined was 88% of the maximum possible points. CONCLUSIONS: The authors used the AirSim Bronchi simulator in a novel simulation curriculum to teach lung-isolation techniques to anesthesiology residents and evaluated performance using a detailed checklist scoring system. This curriculum is a promising educational tool.

Effects of nefopam on early postoperative hyperalgesia after cardiac surgery.

OBJECTIVE: The purpose of this randomized, double-blind placebo-controlled study was to evaluate the effect of nefopam, a centrally acting antinociceptive compound, on the development of hyperalgesia after sternotomy. Preventive strategy giving nefopam from the early stage of anesthesia was compared with a postoperative strategy only and placebo. DESIGN: This study was double-blinded and randomized. SETTING: It was conducted in a single university hospital. PARTICIPANTS: Ninety American Society of Anesthesiologists II to III patients scheduled for elective cardiac surgery. INTERVENTIONS: Patients were assigned randomly to receive a 0.3-mg/kg bolus of nefopam at the induction of anesthesia followed by a continuous infusion of 0.065 mg/kg/h for 48 hours (G1), a 0.3-mg/kg bolus of nefopam at the end of surgery followed by a continuous infusion of 0.065 mg/kg/h for 48 hours (G2), or a placebo (G3). Postoperative analgesia was based on morphine patient-controlled analgesia and rescue analgesia when necessary. Postoperative hyperalgesia, pain scores, morphine consumption, and postoperative cognitive dysfunction were assessed for the first 48 hours and thereafter on postoperative days 4 and 7. MEASUREMENTS AND MAIN RESULTS: The postoperative extent of dynamic hyperalgesia and the decrease of the nociceptive threshold evaluated by von Frey filaments at the sternal midline were smaller in group 1 and group 2 compared with the placebo group at the 24th hour. The primary objective was the extent of hyperalgesia at the midline given as the mean (standard deviation [SD]) (4.4 [2.5] cm for G1, 4.1 [2.7] for G2, and 6.1 [2.7] cm for G3. The punctuate is given as mean (SD) (64 [43] g for G1, 68 [40.8] g for G2, and 32 [27] g for G3; with p < 0.05 for the comparisons of extent and punctuate hyperalgesia between G1 and G3 and G2 and G3). The extent of hyperalgesia was not significantly different among the 3 groups on days 2, 4, and 7 after surgery. There were no significant differences in pain scores, morphine consumption, or postoperative cognitive dysfunctions. CONCLUSIONS: Nefopam administered during the perioperative period slightly reduced acute hyperalgesia after cardiac surgery, but this was not associated with improved analgesic efficacy.

Target-controlled dosing of remifentanil during cardiac surgery reduces postoperative hyperalgesia.

OBJECTIVE: One of the strategies to attenuate opioid-induced hyperalgesia (OIH) may be to decrease intraoperative doses of opioids by using target-controlled infusion (TCI). DESIGN: Double-blind and randomized study. SETTING: A single university hospital. PARTICIPANTS: Forty American Society of Anesthesiologists II to III patients scheduled for elective cardiac surgery. INTERVENTIONS: patients were randomized to 1 of the 2 groups: 1 group received an infusion of intraoperative remifentanil using TCI (target: 7 ng/mL), and the 2nd one was given an intraoperative continuous infusion (CI) (0.3 µg/kg/min). The anesthestic protocol and postoperative pain management were the same in both groups. The extent of mechanical dynamic hyperalgesia on the middle line perpendicular to the wound was considered the primary endpoint. The secondary endpoints were other results of dynamic and punctuate hyperalgesia until postoperative day 7, visual analog scale (VAS) and verbal rating scale (VRS) scores, and total morphine consumption until postoperative day 2. MEASUREMENTS AND MAIN RESULTS: Morphometric and demographic characteristics and duration of surgery were comparable in both groups. Intraoperative remifentanil consumption was greater in CI than in TCI group (5,329 [1,833] v 3,662 [1,160] µg, p = 0.003). During the first 44 hours, there were no differences in morphine consumption, VAS, and VRS. The extent of hyperalgesia was significantly lower on postoperative days 1, 2, and 4 in the TCI group than in the CI group on the 3 evaluated lines (p < 0.05). Punctuate hyperalgesia evaluating 3 different points was lower in the TCI than in the CI group from postoperative day 1 until postoperative day 7 (p < 0.05). CONCLUSIONS: The intraoperative decrease of opioid consumption when comparing the CI versus TCI mode of administration of remifentanil led to less OIH after cardiac surgery.

The IrgA homologue adhesin Iha is an Escherichia coli virulence factor in murine urinary tract infection.

The role of the Escherichia coli iron-regulated gene homologue adhesin (Iha) in the pathogenesis of urinary tract infections (UTIs) is unknown. We performed a series of complementary analyses to confirm or refute the hypothesis that Iha is a virulence factor in uropathogenic E. coli. Fecal E. coli isolates exhibited significantly lower prevalences of iha (range, 14 to 22%) than did clinical isolates from cases of pediatric cystitis or pyelonephritis, adult pyelonephritis or urosepsis, or bacteremia (range, 38 to 74%). Recombinant Iha from E. coli pyelonephritis isolate CFT073 conferred upon nonadherent E. coli ORN172 the ability to adhere to cultured T-24 human uroepithelial cells. In a well-established mouse model of ascending UTI, CFT073 and its derivative UPEC76 (a pap [P fimbriae] mutant version of strain CFT073) each significantly outcompeted their respective iha deletion mutants in CBA/J mice 48 h after bladder challenge (P < 0.03 for urine, both kidneys, and bladders of both constructs, except for bladders of mice challenged with UPEC76 and its deletion mutant, where P = 0.11). These data suggest that Iha(CFT073) is a virulence factor and might be a target for anti-UTI interventions.

Escherichia coli O157:H7 infections: discordance between filterable fecal shiga toxin and disease outcome.

Shiga toxin (Stx)-producing Escherichia coli O157:H7 are the most common cause of hemolytic uremic syndrome (HUS). We detected free fecal Stx in 48%, 40%, and 17% of infected children with uncomplicated diarrhea, children who subsequently developed HUS, and children with HUS, respectively. Vero cell assay detected Stx more frequently than did a commercial Stx enzyme immunoassay. In children's stool samples obtained on or before day 4 of illness, each 10-fold decrease in titer was, paradoxically, associated with 3.8-fold increased odds of developing HUS (P=.03; 95% confidence interval, 0.77-19.7). The fecal Stx type did not correlate with the Stx expressed by bacteria grown in vitro and was not related to bacterial titer in the studied samples. These data suggest that therapeutic and diagnostic strategies directed toward binding or identifying intraintestinal fecal Stx may have limited success.