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.

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.

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.

Cytomegalovirus infection risk with alemtuzumab therapy in hematological malignancies: a retrospective cohort study in the non-transplant setting.

Alemtuzumab is a potent lymphocyte-depleting immunotherapy used in solid organ transplan-tation (SOT), that is increasingly being applied in diverse lymphoproliferative disorders (LPDs). However, a significant toxicity limiting expanded usage is cytomegalovirus (CMV) infection, for which standardized preventive strategies exist in SOT but not in LPDs due to a poor understanding of infection risk in this population, with early LPD studies largely limited to stem cell transplantation. Using one of the most diverse arrays of LPDs studied to date, our retrospective cohort study of non-transplant patients receiving alemtuzumab over a ten-year period at a large regional cancer center examines the incidence and clinical profile of infected patients. Among 24 patients, we identified a composite CMV infection rate of 42% with a symptomatic rate of 21%. We also noted significant variations in preventive strategies, which alongside a high infection rate presents an opportunity to improve outcomes through further work in standardization.

Factors influencing the use of highly bioavailable oral antibiotic therapy for the treatment of prosthetic joint infections.

We conducted a retrospective cohort study to identify factors influencing intravenous (IV) versus oral antibiotic therapy in first-episode prosthetic joint infections. Of the 34/78 (44%) cases treated intravenously, negative cultures (26%), concomitant infections necessitating IV antibiotics (21%), and delays in susceptibility testing (15%) were the most common reasons for IV therapy.

Addition of anaerobic coverage for treatment of biliary tract infections: a propensity score-matched cohort study.

Objectives: To evaluate whether additional antibiotics that target anaerobes, including Bacteroides spp., are associated with improved clinical outcomes in patients with biliary tract infections (BTIs). Methods: This was a retrospective propensity score-matched cohort of adults aged ≥18 years with BTIs, admitted to hospital between 1 April 2015 and 30 March 2021. Eligible patients treated with antibiotics that provided coverage of anaerobes were compared with those treated with comparable regimens without anaerobic coverage. The primary outcome was a composite of mortality within 30 days or relapse within 90 days of source control or completion of antibiotics. Secondary outcomes included length of stay (LOS), duration of antibiotic therapy and adverse drug reactions. ORs were calculated using a weighted generalized linear regression model with propensity-score matching. Results: Among 398 patients included, 209 were treated without anaerobic coverage and 189 with anaerobic coverage. After propensity-score matching, there was no significant difference in primary outcome between propensity-matched patients who received additional anaerobic coverage and those who did not [adjusted OR (aOR) 1.23; 95% CI 0.69-2.22)]. Those with anti-anaerobic coverage had longer LOS (aOR 4.85; 95% CI 1.68-13.98) and longer duration of antibiotic treatment (aOR 4.14; 95% CI 2.61-6.57) than those who did not receive additional anaerobic therapy, but not more adverse drug reactions (aOR 1.01; 95% CI 0.97-1.05). Conclusions: Omitting anti-anaerobic antibiotics may be a safe antimicrobial stewardship intervention. However, a randomized controlled trial may be warranted to definitively conclude whether additional anaerobic coverage in BTI treatment is necessary.

Patient predictors of pathogenic versus commensal Gram-positive bacilli organisms isolated from blood cultures.

Objective: Gram-positive bacilli represent a diverse species of bacteria that range from commensal flora to pathogens implicated in severe and life-threatening infection. Following the isolation of Gram-positive bacilli from blood cultures, the time to species identification may take upward of 24 hours, leaving clinicians to conjecture whether they may represent a contaminant (inadvertent inoculation of commensal flora) or pathogenic organism. In this study, we sought to identify patient variables that could help predict the isolation of contaminant versus pathogenic Gram-positive bacilli from blood cultures. Design: Retrospective cohort study. Settings: One quaternary academic medical center affiliated with the University of Toronto. Patients: Adult inpatients were admitted to hospital over a 5-year period (May 2014 to December 2019). Methods: A total of 260 unique Gram-positive bacilli blood culture results from adult inpatients were reviewed and analyzed in both a univariable and multivariable model. Results: Malignancy (aOR 2.78, 95% CI 1.33-5.91, p = 0.007), point increments in the Quick Sepsis Related Organ Failure Assessment score for sepsis (aOR 2.25, 95% CI 1.50-3.47, p < 0.001), peptic ulcer disease (aOR 5.63, 95% CI 1.43-21.0, p = 0.01), and the receipt of immunosuppression prior to a blood culture draw (aOR 3.80, 95% CI 1.86-8.01, p < 0.001) were associated with an increased likelihood of speciating pathogenic Gram-positive bacilli from blood cultures such as Clostridium species and Listeria monocytogenes. Conclusion: Such predictors can help supplement a clinician's assessment on determining when empirical therapy is indicated when faced with Gram-positive bacilli from blood cultures and may direct future stewardship interventions for responsible antimicrobial prescribing.

A sepsis treatment algorithm to improve early antibiotic de-escalation while maintaining adequacy of coverage (Early-IDEAS): A prospective observational study.

BACKGROUND: Empiric antibiotic treatment selection should provide adequate coverage for potential pathogens while minimizing unnecessary broad-spectrum antibiotic use. We sought to pilot a sepsis treatment algorithm to individualize antibiotic recommendations, and thereby improve early antibiotic de-escalation while maintaining adequacy of coverage (Early-IDEAS). METHODS: In this observational study, the Early-IDEAS decision support algorithm was derived from previous Gram- negative and Gram-positive prediction rules and models along with local guidelines, and then applied to prospectively identified consecutive adults within 24 hours of suspected sepsis. The primary outcome was the proportion of patients for whom de-escalation of the primary antibiotic regimen was recommended by the algorithm. Secondary outcomes included: (1) proportion of patients for whom escalation was recommended; (2) number of recommended de-escalation steps along a pre-specified antibiotic cascade; and (3) adequacy of therapy in patients with culture-confirmed infection. RESULTS: We screened 578 patients, of whom 107 eligible patients were included. The Early-IDEAS treatment recommendation was informed by Gram-negative models in 76 (71%) patients, Gram-positive rules in 64 (59.8%), and local guidelines in 27 (25.2%). Antibiotic de-escalation was recommended in almost half of all patients (n = 52, 48.6%), with a median of 2 steps down the a priori antibiotic treatment cascade. No treatment change was recommended in 45 patients (42.1%), and escalation was recommended in 10 (9.3%). Among the 17 patients with positive blood cultures, both the clinician prescribed regimen and the algorithm recommendation provided adequate coverage for the isolated pathogen in 12 patients (70.6%), (p = 1). Among the 25 patients with positive relevant, non-blood cultures, both the clinician prescribed regimen and the algorithm recommendation provided adequate coverage in 20 (80%), (p = 1). CONCLUSION: An individualized decision support algorithm in early sepsis could lead to substantial antibiotic de-escalation without compromising adequate antibiotic coverage.