Antibiotic-Induced Neutropenia in Patients Receiving Outpatient Parenteral Antibiotic Therapy: a Retrospective Cohort Study.

Our research objective was to describe the incidence and management of antibiotic-induced neutropenia in patients receiving outpatient parenteral antibiotic therapy (OPAT) at our institution over a 7-year period. We conducted a retrospective cohort study of patients followed by the OPAT clinic from 1 July 2016 to 30 March 2022 who developed antibiotic-induced neutropenia (defined as an absolute neutrophil count of ≤1.5 × 109/L). Patients receiving vancomycin in the OPAT clinic received weekly laboratory monitoring, while those receiving other antibiotics received laboratory monitoring at week 3 of therapy. Out of the 2,513 treatment courses, 55 cases of antibiotic-induced neutropenia were identified, resulting in an incidence of 2.2 cases per 100 treatment courses (95% confidence interval [CI], 1.7 to 2.9). Of the 45 cases for which a sole cause was identified, the three most common intravenous antibiotic culprits were vancomycin (21/541; 3.9%), ceftriaxone (10/490; 2.0%), and cloxacillin (2/103; 1.9%). Five (9.1%) patients had symptoms accompanying neutropenia that warranted hospital admission. There were no deaths, and all patients recovered their neutrophil count after antibiotic discontinuation or completion. In nine cases (16.3%), the culprit beta-lactam antibiotic was changed to another beta-lactam agent containing a structurally different side chain, with successful recovery of the neutrophil count in 9/9 (100%). The highest risk of antibiotic-induced neutropenia was associated with vancomycin, ceftriaxone, and cloxacillin in our cohort. With standardized outpatient monitoring during the third week of OPAT, cases of neutropenia can be detected early and managed without hospitalization. Data from our study also support the safety of switching to alternate beta-lactams with structurally different side chains.

Optimizing Cefazolin Prophylaxis in Obstetrical Patients with Reported Beta-Lactam Allergy Undergoing Cesarean Delivery.

OBJECTIVES: Evaluate the impact of an allergy history-guided algorithm for optimizing perioperative cefazolin use in patients with reported beta-lactam allergy undergoing cesarean delivery. METHODS: The Allergy Clarification for Cefazolin Evidence-based Prescribing Tool (ACCEPT) was developed through consensus by allergists, anesthesiologists, and infectious diseases specialists, and implemented over a 2-month period (December 1, 2018, to January 31, 2019). A segmented regression on monthly cefazolin use was conducted during the baseline (January 1 to November 30, 2018) and intervention (February 1 to December 31, 2019) periods to evaluate the impact of ACCEPT on the monthly use of perioperative cefazolin in patients with reported beta-lactam allergy undergoing cesarean delivery. The frequency of perioperative allergic reactions and surgical site infections was collected during both periods. RESULTS: Of the 3128 eligible women who underwent a cesarean delivery, 282 (9%) reported a beta-lactam allergy. The most common beta-lactam allergens were penicillin (64.3%), amoxicillin (16.0%), and cefaclor (6.0%). The most frequently reported allergic reactions were rash (38.1%), hives (21.4%), and unknown (11.6%). Use of cefazolin increased from 52% (baseline) to 87% during the intervention period. Segmented regression analysis confirmed a statistically significant increase following implementation (incidence rate ratio 1.62, 95% CI 1.19-2.21, P = 0.002). There was 1 perioperative allergic reaction in the baseline period and 2 during the intervention period. Cefazolin use remained high (92%) 2 years after algorithm implementation. CONCLUSIONS: Implementation of a simple allergy history-guided algorithm in obstetrical patients with reported beta-lactam allergy resulted in a sustained increase in perioperative cefazolin prophylaxis.

Introducing the Escalation Antibiogram: A Simple Tool to Inform Changes in Empiric Antimicrobials in the Nonresponding Patient.

BACKGROUND: Hospital antibiograms guide initial empiric antibiotic treatment selections, but do not directly inform escalation of treatment among nonresponding patients. METHODS: Using gram-negative bacteremia as an exemplar condition, we sought to introduce the concept of an escalation antibiogram. Among episodes of gram-negative bacteremia between 2017 and 2020 from 6 hospitals in the Greater Toronto Area, we generated escalation antibiograms for each of 12 commonly used agents. Among organisms resistant to that antibiotic, we calculated the likelihood of susceptibility to each of the other 11 agents. In subgroup analyses, we examined escalation antibiograms across study years, individual hospitals, community versus hospital onset, and pathogen type. RESULTS: Among 6577 gram-negative bacteremia episodes, the likelihood of coverage was ampicillin 31.8%, cefazolin 62.7%, ceftriaxone 67.1%, piperacillin-tazobactam 72.5%, ceftazidime 74.1%, trimethoprim-sulfamethoxazole 74.4%, ciprofloxacin 77.1%, tobramycin 88.3%, gentamicin 88.8%, ertapenem 91.0%, amikacin 97.5%, and meropenem 98.2%. The escalation antibiograms revealed marked shifts in likelihood of coverage by the remaining 11 agents. For example, among ceftriaxone-resistant isolates, piperacillin-tazobactam susceptibility (21.2%) was significantly lower than trimethoprim-sulfamethoxazole (54.2%, P < .0001), ciprofloxacin (63.0%, P < .0001), ertapenem (73.4%, P < .0001), tobramycin (80.1%, P < .0001), gentamicin (82.8%, P < .0001), meropenem (94.3%, P < .0001), and amikacin (97.1%, P < .0001). Trimethoprim-sulfamethoxazole was the second-ranked agent in the meropenem escalation antibiogram (49.6%) and first in the amikacin escalation antibiogram (86.0%). Escalation antibiograms were consistent across 4 study years and 6 hospitals. CONCLUSIONS: Escalation antibiograms can be generated to inform empiric treatment changes in nonresponding patients. These tools can yield important insights such as avoiding the common maneuver of escalating from ceftriaxone to piperacillin-tazobactam in suspected gram-negative bacteremia.

Improving Intrapartum Group B Streptococcus Prophylaxis in Patients with a Reported Penicillin or Cephalosporin Allergy: A Quality Improvement Project.

OBJECTIVE: To evaluate the impact of a standardized allergy-guided approach to Group B Streptococcus (GBS) prophylaxis in pregnant women with reported penicillin or cephalosporin allergy. METHODS: This interrupted time-series analysis included obstetric patients requiring GBS prophylaxis who reported penicillin or cephalosporin allergies. Patients were divided into baseline (April 1, 2019 to July 21, 2020) and intervention (July 22, 2020 to July 31, 2021) groups. The primary outcome was prophylaxis appropriateness, based on antibiotic type, nature of reaction, and cross-reactivity risk. Secondary outcomes included type of prophylaxis received and antibiotic-related adverse events. RESULTS: The study included 88 patients in the baseline period and 52 patients in the intervention period. Appropriate prophylaxis increased from 47% (41/88) to 85% (44/52), with the segmented regression model confirming a statistically significant increase over time (incidence rate ratio 1.57; 95% CI 1.02-2.43, P = 0.04, slope coefficient 1.06/month; 95% CI 1.01-1.10, P = 0.01). Penicillin and cefazolin use increased from 61% (54/88) to 87% (45/52) in the intervention period (P = 0.002), and no hypersensitivity reactions occurred during this period. CONCLUSIONS: Implementation of standardized allergy-guided prophylaxis safely improved appropriate ß-lactam antibiotic use in obstetric patients requiring GBS prophylaxis who reported penicillin and cephalosporin allergies.

Using Virtual Care to Facilitate Direct Hospital Admissions in Outpatients with Worsening COVID-19 Infection.

Recognizing emergency department overcrowding during the COVID-19 pandemic, a pathway to facilitate direct admissions for outpatients with worsening COVID-19 infection was created using the COVID-19 expansion to outpatients (COVIDEO) virtual care program. Outpatients appropriate for direct admission had oxygen saturations consistently <92% without severe respiratory distress. Pulse oximeters were proactively delivered to high-risk patients, and patients contacted the program in the event of worsening symptoms or desaturation persistently <92%. Over a 15-month period, 9,116 outpatients were managed by the program, 164 of whom were hospitalized, and 83 of those hospitalized (50.6%) were directly admitted through this pathway. Of those directly admitted, 10 (12.0%) patients required ICU admission, occurring a median of 4 days from hospital admission. The mortality rate among directly admitted patients was 3.6% (3/83). Implementation of a virtual care program to facilitate direct admissions in outpatients with COVID-19 created a safe, efficient, and patient-centered pathway of care.

Long-Term Sustainability and Acceptance of Antimicrobial Stewardship in Intensive Care: A Retrospective Cohort Study.

OBJECTIVES: To evaluate long-term uptake of an antimicrobial stewardship audit-and-feedback program along with potential predictors of stewardship suggestions and acceptance across a diverse ICU population. DESIGN: A retrospective cohort study. SETTING: An urban, academic medical institution. PATIENTS: Patients admitted to an ICU who received an antimicrobial stewardship program suggestion between June 2010 and September 2019. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The antimicrobial stewardship program provided 7,749 antibiotic assessments over the study period and made a suggestion to alter therapy in 2,826 (36%). Factors associated with a higher likelihood of receiving a suggestion to alter therapy included shorter hospital length of stay prior to antimicrobial stewardship program review (odds ratio 1.15 for ≤ 5 d; 95% CI 1.00-1.32), admission to cardiovascular (1.37; 1.06-1.76) or burn surgery (1.88; 1.50-2.36) versus general medicine, and preceding duration of antibiotic use greater than 5 days (1.33; 1.10-1.60). Assessment of aminoglycosides (2.91; 1.85-4.89), carbapenems (1.93; 1.54-2.41), and vancomycin (2.71; 2.19-3.36) versus ceftriaxone was more likely to result in suggestions to alter therapy. The suggestion acceptance rate was 67% (1,895/2,826), which was stable throughout the study period. Admission to a level 3 ICU was associated with higher likelihood of acceptance of suggestions (1.50; 1.14-1.97). Factors associated with lower acceptance rates were admission to burn surgery (0.64; 0.45-0.91), treatment of pneumonia (0.64; 0.42-0.97 for community-acquired and 0.65; 0.44-0.94 for ventilator-acquired), unknown source of infection (0.66; 0.48-0.92), and suggestion types of "narrow spectrum" (0.65; 0.45-0.94), "change formulation of antibiotic" (0.42; 0.27-0.64), or "change agent of therapy" (0.63; 0.40-0.97) versus "change of dose". CONCLUSIONS: An antimicrobial stewardship program implemented over a decade resulted in sustained suggestion and acceptance rates. These findings support the need for a persistent presence of audit-and-feedback over time with more frequent suggestions to alter potentially nephrotoxic agents, increased efforts toward specialized care units, and further work approaching infectious sources that are typically treated without pathogen confirmation and identification.

Impact of the Allergy Clarification for Cefazolin Evidence-based Prescribing Tool on Receipt of Preferred Perioperative Prophylaxis: An Interrupted Time Series Study.

Implementation of a perioperative allergy and antibiotic assessment tool in patients with reported beta-lactam allergy resulted in a pronounced and sustained increase in perioperative cefazolin use. This intervention could result in improved efficiencies surrounding perioperative antibiotic administration and possible reductions in surgical site infection rates.

Effects of a potassium channel opener on brain injury and neurologic outcomes in an animal model of neonatal hypoxic-ischemic injury.

BACKGROUND: Hypoxia-ischemia (HI) is the most common cause of brain injury in newborns and the survivors often develop cognitive and sensorimotor disabilities that undermine the quality of life. In the current study, we examined the effectiveness of flupirtine, a potassium channel opener, shown previously in an animal model to have strong anti-neonatal-seizure efficacy, to provide neuroprotection and alleviate later-life disabilities caused by neonatal hypoxic-ischemic injury. METHODS: The rats were treated with a single dose of flupirtine for 4 days following HI induction in 7-day-old rats. The first dose of flupirtine was given after the induction of HI and during the reperfusion period. The effect of treatment was examined on acute and chronic brain injury, motor functions, and cognitive abilities. RESULTS: Flupirtine treatment significantly reduced HI-induced hippocampal and cortical tissue loss at acute time point. Furthermore, at chronic time point, flupirtine reduced contralateral hippocampal volume loss and partially reversed learning and memory impairments but failed to improve motor deficits. CONCLUSION: The flupirtine treatment regimen used in the current study significantly reduced brain injury at acute time point in an animal model of neonatal hypoxic-ischemic encephalopathy. However, these neuroprotective effects were not persistent and only modest improvement in functional outcomes were observed at chronic time points.

Comparison of central corneal thickness measurement by scanning slit topography, infrared, and ultrasound pachymetry in normal and post-LASIK eyes.

OBJECTIVES: To compare central corneal thickness (CCT) measurements by scanning slit topography (SST), infrared pachymetry (IRP), and ultrasound pachymetry (USP), and their agreement in normal and post-laser in situ keratomileusis (LASIK) eyes. METHODS: Sixty normal and 35 post-LASIK subjects were recruited. Only one eye from each subject was analyzed. Non-contact pachymetry was performed first, and the order for SST (Orbscan IIz) and IRP (Tonoref III) was randomized for each patient, to be followed by contact USP (Echoscan US-4000). Pearson's correlation, paired t test, and Bland-Altman plots were used to investigate association, difference, and agreement among different instruments respectively. RESULTS: The measurements obtained with the instruments were highly correlated. Compared to CCT determined by USP (CCTUSP), CCT determined by SST (after correction with acoustic factor) (CCTSSTC) was thicker by 7 µm in normal eyes (P < 0.001). There was no significant difference between CCTSSTC and CCTUSP (P = 0.128), but a thickness-dependent deviation in post-LASIK eyes (P = 0.003). The CCT determined by IRP (CCTIRP) was thicker than CCTUSP in normal (P < 0.001) and post-LASIK eyes (P < 0.001) and demonstrated proportional overestimation with thinner corneas, with less predictable ultrasonic equivalent corneal thickness in normal eyes. Conversely, CCTIRP significantly underestimated CCT compared to CCTSST and showed increasing underestimation with thinner corneas in both normal and post-LASIK eyes (both P < 0.001). CONCLUSION: Central corneal thickness determined by SST, IRP and USP were not interchangeable or interconvertible, probably attributed to difference in methodologies. Compensation with algorithms may improve agreements amongst instruments.

Calpain activation and neuronal death during early epileptogenesis.

Epilepsy is a brain disorder characterized by a predisposition to suffer epileptic seizures. Acquired epilepsy might be the result of brain insults like head trauma, stroke, brain infection, or status epilepticus (SE) when one of these triggering injuries starts a transformative process known as epileptogenesis. There is some data to suggest that, during epileptogenesis, seizures themselves damage the brain but there is no conclusive evidence to demonstrate that spontaneous recurrent seizures themselves injure the brain. Our recent evidence indicates that calpain overactivation might be relevant for epileptogenesis. Here, we investigated if spontaneous recurrent seizures that occur during an early period of epileptogenesis show any correlation with the levels of calpain activation and/or expression. In addition, we also investigated a possible association between the occurrence of spontaneous seizures and increased levels of cell death, gliosis and inflammation (typical markers associated with epileptogenesis). We found that the number of spontaneous seizures detected prior to sample collection was correlated with altered calpain activity and expression. Moreover, the levels of hippocampal neurodegeneration were also correlated with seizure occurrence. Our findings suggest that, at least during early epileptogenesis, there is a correlation between seizure occurrence, calpain activity and neurodegeneration. Thus, this study opens the possibility that aberrant calpain reactivation by spontaneous seizures might contribute to the manifestation of future spontaneous seizures.

Utility of Urine Cultures in Predicting Blood Culture Susceptibilities in Patients with Bacteremic Urinary Tract Infection.

In a review of 428 patients with bacteremic urinary tract infections, urine culture susceptibility results accurately predicted blood culture results when the same organism was isolated from both cultures. Early targeted therapy using urine culture results can potentially reduce broad-spectrum antibiotic exposure and its associated adverse effects and the length of hospitalization.

Impact of Defaulting to Single-Lumen Peripherally Inserted Central Catheters on Patient Outcomes: An Interrupted Time Series Study.

Defaulting to single-lumen peripherally inserted central catheters (PICCs) ordered from non-critical care units resulted in a sustained reduction in PICC-related complications. This system of care is transferrable to other institutions, with potential for improved patient safety and efficiency in outpatient parenteral antimicrobial therapy clinics.

Predictors of Peripherally Inserted Central Catheter Occlusion in the Outpatient Parenteral Antimicrobial Therapy Setting.

In this retrospective study of 285 patients receiving outpatient parenteral antibiotic therapy (OPAT), the duration of antibiotic, use of double-lumen catheters, and receipt of penicillin G and cloxacillin appeared to increase the risk of peripherally inserted central catheter (PICC) occlusion. Physicians should consider these factors when prescribing long-term antibiotic therapy. Further studies are needed to evaluate methods to reduce PICC occlusion, particularly when double-lumen PICCs are necessary and when cloxacillin or penicillin G are the preferred treatment.

A calpain inhibitor ameliorates seizure burden in an experimental model of temporal lobe epilepsy.

In this study, we used the pilocarpine model of epilepsy to evaluate the involvement of calpain dysregulation on epileptogenesis. Detection of spectrin breakdown products (SBDPs, a hallmark of calpain activation) after induction of pilocarpine-induced status epilepticus (SE) and before appearance of spontaneous seizure suggested the existence of sustained calpain activation during epileptogenesis. Acute treatment with a cell permeable inhibitor of calpain, MDL-28170, resulted in a partial but significant reduction on seizure burden. The reduction on seizure burden was associated with a limited reduction on the generation of SBDPs but was correlated with a reduction in astrocytosis, microglia activation and cell sprouting. Together, these observations provide evidence for the role of calpain in epileptogenesis. In addition, provide proof-of-principle for the use of calpain inhibitors as a novel strategy to prevent epileptic seizures and its associated pathologies.

Introducing Final-Year Medical Students to Pocket-Sized Ultrasound Imaging: Teaching Transthoracic Echocardiography on a 2-Week Anesthesia Rotation.

PROBLEM: The availability of less expensive and smaller ultrasound machines has enabled the use of ultrasound in virtually all major medical/surgical disciplines. Some medical schools have incorporated point-of-care ultrasound training into their undergraduate curriculum, whereas many postgraduate programs have made ultrasound training a standard. The Chinese University of Hong Kong has charged its Department of Anaesthesia and Intensive Care to spearhead the introduction of ultrasound into the final-year medical curriculum by introducing handheld transthoracic echocardiography as part of perioperative assessment. INTERVENTION: All 133 final-year students completed a 2-week anesthesia rotation, which began with a half-day session consisting of a lecture and hands-on practice session during which they learned 9 basic transthoracic echocardiography views using 4 basic ultrasound probe positions. CONTEXT: Each student was required to perform a transthoracic echocardiography-examine under supervision of 1 patient/week for 2 weeks, and their results were compared against that of the supervisor's. Most patients were elective cardiac surgery patients. One long question on transthoracic echocardiography was included in their end-of-year surgery examination paper. Students provided feedback on their experience. OUTCOME: Most students learned the basic transthoracic echocardiography views fairly efficiently and had variable, though generally favorable, success rates in identifying obvious cardiac anomalies, including use of color Doppler. A few common mistakes were identified but were easily correctable. Logistics for mobilizing enough bedside supervision were challenging. Students reported positive feedback on the teaching initiative. LESSONS LEARNED: We were able to execute a successful short training course on transthoracic echocardiography during the final-year medical degree anesthesia rotation. Our initiative may set an example for other clinical departments to design similar courses pertinent to their specialties and syllabuses.

Pasteurella multocida non-native joint infection after a dog lick: A case report describing a complicated two-stage revision and a comprehensive review of the literature.

Prosthetic joint infections (PJIs) are commonly caused by pathogens such as Staphylococcus aureus and coagulase-negative staphylococci; however, other microbial etiologies and specific risk factors are increasingly recognized. Pasteurella multocida is a Gram-negative coccobacillus that is part of the normal oral flora in many animals, and is particularly common in dogs and cats. PJIs caused by P multocida have been reported only rarely in the literature and typically occur in the context of an animal bite or scratch. The present article describes a P multocida joint infection that occurred after a dog lick and complicated a two-stage revision arthroplasty. A comprehensive review of the literature regarding P multocida PJIs follows.

Les infections sur prothèse articulaire (IPA) sont souvent causées par des pathogènes comme le Staphylococcus aureus et les staphylocoques à coagulase négative. Cependant, on constate de plus en plus d'autres étiologies microbiennes et de facteurs de risque particuliers. Le Pasteurella multocida, un coccobacille à Gram négatif qui fait partie de la flore orale normale de nombreux animaux, est particulièrement courant chez les chiens et les chats. Peu d'IPA causées par le P multocida sont signalées dans les publications scientifiques, mais elles se produisent surtout après une morsure ou une griffure d'animal. Le présent article décrit une infection à P multocida qui s'est manifestée après que l'articulation a été léchée par un chien et une arthroplastie de révision compliquée en deux étapes. Une analyse bibliographique approfondie de l'IPA à P multocida suit.

Raoultella planticola bacteremia following consumption of seafood.

Raoultella planticola is a Gram-negative bacillus commonly found in water, soil and aquatic environments. There have only been 16 cases of R planticola infection documented in the literature to date. R planticola possesses the ability to convert histidine to histamine and can produce symptoms of scombroid poisoning when poorly prepared seafood is consumed in large amounts. The present report describes a case involving a 56-year-old woman who presented with R planticola bacteremia and symptoms consistent with cholangitis four days after consuming a seafood salad containing squid and octopus. She was successfully treated with intravenous ceftriaxone followed by oral ciprofloxacin. Recent chemotherapy, proton pump inhibitor use and altered biliary flow secondary to hepatic metastases may have been contributing factors to the pathogenesis of disease.

La Raoultella planticola est un bacille à Gram négatif qu'on trouve souvent dans l'eau, la terre et les milieux aquatiques. Seulement 16 cas d'infection à R planticola ont été répertoriés dans les publications jusqu'à présent. Le R planticola peut convertir l'histidine en histamine et produire des symptômes de scombroïdose après la consommation de grandes quantités de fruits de mer mal préparés. Le présent rapport décrit le cas d'une femme de 56 ans qui a consulté à cause d'une bactériémie à R planticola et de symptômes évocateurs d'une cholangite quatre jours après avoir consommé une salade de fruits de mer contenant du calmar et de la pieuvre. Elle a été traitée avec succès au moyen de ceftriaxone par voie intraveineuse suivie de ciprofloxacine par voie orale. Une récente chimiothérapie, la prise d'inhibiteurs de la pompe à protons et une perturbation de l'écoulement biliaire secondaire à des métastases hépatiques peuvent avoir contribué à la pathogenèse de la maladie.