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Jeffrey Tessier, MD

Actinomyces turicensis Necrotizing Soft-Tissue Infection of the Thigh in a Diabetic Male.

Wed, 02/27/2019 - 15:16
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Actinomyces turicensis Necrotizing Soft-Tissue Infection of the Thigh in a Diabetic Male.

Surg Infect (Larchmt). 2019 Feb 21;:

Authors: Panwar K, Duane TM, Tessier JM, Patel K, Sanders JM

BACKGROUND: Necrotizing soft-tissue infections are a devastating infection that is rarely caused by Actinomyces spp.
CASE REPORT: A 45-year-old obese previously healthy male presented to the emergency department with diabetic ketoacidosis. The patient developed systemic signs of infections and right medial thigh pain subsequently diagnosed as a necrotizing soft-tissue infection. Successful treatment included prompt surgical intervention and initiation of broad-spectrum antimicrobial drugs.
CONCLUSION: Actinomyces turicensis may be the pathogen causing certain necrotizing soft-tissue infections. Clinicians should consider the possibility that this organism represents a true pathogen and not colonization/contamination.

PMID: 30789313 [PubMed - as supplied by publisher]

Measuring Provider Compliance with an Institution-Based Clinical Pathway for Diverticulitis Using Radiologic Criteria.

Wed, 01/30/2019 - 08:22
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Measuring Provider Compliance with an Institution-Based Clinical Pathway for Diverticulitis Using Radiologic Criteria.

Surg Infect (Larchmt). 2018 Oct;19(7):655-660

Authors: Gonzalez G, Montemayor E, Sanders JM, Burton M, Tessier JM, Duane TM

BACKGROUND: Diverticulitis remains a common disease encountered in the acute care setting. Management strategies have been developed to guide treatment decisions based on imaging. By using a multi-faceted clinical pathway approach, a standardized method of diagnosing and categorizing disease severity can be performed in order to guide appropriate management. This study evaluated provider compliance with an institutional clinical pathway designed to guide management of diverticulitis.
METHODS: An institutional clinical pathway was developed to manage diverticulitis, including radiologic classification, primary service line assignment, interventional strategies, and antimicrobial treatment. To assess provider compliance with the algorithm, we queried the institutional acute diverticulitis database for patients admitted from May 19, 2016 to February 8, 2017, which identified 83 patients. Provider compliance with the pathway was assessed using subgroup analysis of radiologic documentation (modified Neff [mNeff] classification), primary service assignment, and interventions (i.e., interventional radiology [IR] and antimicrobial agents).
RESULTS: The cohort represented a diverse group of mNeff classifications, predominantly Stage 0. Surgical interventions occurred in 10.8% of the cohort. Antimicrobial agents were administered to 88.0% and 78.3% of the outpatients and inpatients, respectively. Patients received a total duration of antimicrobial therapy (mean ± standard deviation [SD]) of 10.2 ± 5.1 days. Overall compliance occurred in 10% of the patients. Compliance with radiologic documentation, antimicrobial choice, and antimicrobial duration were 90.4%, 20.5%, and 69.9%, respectively.
CONCLUSIONS: Overall compliance with the clinical pathway was poor, except as it related to compliance with radiologic documentation, appropriate assignment to surgical service line, and antimicrobial duration. These results suggest areas for future improvement to augment compliance with the clinical pathway.

PMID: 30179571 [PubMed - indexed for MEDLINE]

Does Isolation of Enterococcus Affect Outcomes in Intra-Abdominal Infections?

Wed, 10/11/2017 - 05:00

Surg Infect (Larchmt). 2017 Nov/Dec;18(8):879-885. doi: 10.1089/sur.2017.121. Epub 2017 Oct 10.


BACKGROUND: Enterococci are isolated frequently as pathogens in patients with intra-abdominal infections (IAIs) and may predict poor clinical outcomes. It remains controversial whether enterococci warrant an altered treatment approach with regard to antimicrobial treatment.

PATIENTS AND METHODS: The study population was derived from the Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial database. Through post hoc analysis subjects were stratified into two groups based on isolation of Enterococcus. Fifty subjects of the cohort (n = 518) had Enterococcus isolated. Uni-variable and multi-variable analyses were conducted to determine whether isolation of Enterococcus constituted an independent predictor of the pre-defined STOP-IT composite outcome (surgical site infection, recurrent IAI, or death) and the individual components of the composite outcome.

RESULTS: From the cohort of 50 subjects, we identified 52 isolates of Enterococcus spp. with a predominance of Enterococcus faecalis (40%) followed by other Enterococcus spp. (37%) and Enterococcus faecium (17%). Baseline demographic characteristics were statistically similar between the two groups. Antibiotic utilization distribution remained balanced between the Enterococcus and no Enterococcus groups with the majority receiving piperacillin-tazobactam (62% and 54%, respectively). The groups had comparable infection characteristics including setting of acquisition (>50% community acquired) and origin of infection (predominantly colon or rectum). Individual and composite clinical outcomes were not different statistically between the Enterococcus and no Enterococcus groups: surgical site infection (10% vs. 7.5%; p = 0.53), recurrent IAI (20% vs. 14.1%; p = 0.26), death (2% vs. 1%; p = 0.40), and composite of all three (30% vs. 20.9%; p = 0.14], respectively. Multi-variable analysis revealed that isolation of Enterococcus did not predict independently the incidence of the composite outcome (odds ratio [OR] 1.53 [95% confidence interval {CI} = 0.78-3.01]; p = 0.22; c-statistic = 0.65; goodness of fit, p = 0.71).

CONCLUSIONS: Enterococcus was not a more common pathogen in health-care-associated IAIs and was not an independent risk factor for the composite outcome. The isolation of Enterococcus from IAIs may not warrant an alternative treatment approach but larger studies are needed to validate these findings.

PMID:28994635 | DOI:10.1089/sur.2017.121

The <em>Global Alliance for Infections in Surgery:</em> defining a model for antimicrobial stewardship-results from an international cross-sectional survey

Sat, 08/05/2017 - 05:00

World J Emerg Surg. 2017 Aug 1;12:34. doi: 10.1186/s13017-017-0145-2. eCollection 2017.


BACKGROUND: Antimicrobial Stewardship Programs (ASPs) have been promoted to optimize antimicrobial usage and patient outcomes, and to reduce the emergence of antimicrobial-resistant organisms. However, the best strategies for an ASP are not definitively established and are likely to vary based on local culture, policy, and routine clinical practice, and probably limited resources in middle-income countries. The aim of this study is to evaluate structures and resources of antimicrobial stewardship teams (ASTs) in surgical departments from different regions of the world.

METHODS: A cross-sectional web-based survey was conducted in 2016 on 173 physicians who participated in the AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections) project and on 658 international experts in the fields of ASPs, infection control, and infections in surgery.

RESULTS: The response rate was 19.4%. One hundred fifty-six (98.7%) participants stated their hospital had a multidisciplinary AST. The median number of physicians working inside the team was five [interquartile range 4-6]. An infectious disease specialist, a microbiologist and an infection control specialist were, respectively, present in 80.1, 76.3, and 67.9% of the ASTs. A surgeon was a component in 59.0% of cases and was significantly more likely to be present in university hospitals (89.5%, p < 0.05) compared to community teaching (83.3%) and community hospitals (66.7%). Protocols for pre-operative prophylaxis and for antimicrobial treatment of surgical infections were respectively implemented in 96.2 and 82.3% of the hospitals. The majority of the surgical departments implemented both persuasive and restrictive interventions (72.8%). The most common types of interventions in surgical departments were dissemination of educational materials (62.5%), expert approval (61.0%), audit and feedback (55.1%), educational outreach (53.7%), and compulsory order forms (51.5%).

CONCLUSION: The survey showed a heterogeneous organization of ASPs worldwide, demonstrating the necessity of a multidisciplinary and collaborative approach in the battle against antimicrobial resistance in surgical infections, and the importance of educational efforts towards this goal.

PMID:28775763 | PMC:PMC5540347 | DOI:10.1186/s13017-017-0145-2

Antibiotics vs. Appendectomy for Acute Uncomplicated Appendicitis in Adults: Review of the Evidence and Future Directions

Thu, 06/15/2017 - 05:00

Surg Infect (Larchmt). 2017 Jul;18(5):527-535. doi: 10.1089/sur.2017.073. Epub 2017 Jun 14.


BACKGROUND: Acute appendicitis is the most common abdominal surgical emergency in the United States, with a lifetime risk of 7%-8%. The treatment paradigm for complicated appendicitis has evolved over the past decade, and many cases now are managed by broad-spectrum antibiotics. We determined the role of non-operative and operative management in adult patients with uncomplicated appendicitis.

METHODS: Several meta-analyses have attempted to clarify the debate. Arguably the most influential is the Appendicitis Acuta (APPAC) Trial.

RESULTS: According to the non-inferiority analysis and a pre-specified non-inferiority margin of -24%, the APPAC did not demonstrate non-inferiority of antibiotics vs. appendectomy. Significantly, however, the operations were nearly always open, whereas the majority of appendectomies in the United States are done laparoscopically; and laparoscopic and open appendectomies are not equivalent operations. Treatment with antibiotics is efficacious more than 70% of the time. However, a switch to an antimicrobial-only approach may result in a greater probability of antimicrobial-associated collateral damage, both to the host patient and to antibiotic susceptibility patterns. A surgery-only approach would result in a reduction in antibiotic exposure, a consideration in these days of focus on antimicrobial stewardship.

CONCLUSION: Future studies should focus on isolating the characteristics of appendicitis most susceptible to antibiotics, using laparoscopic operations as controls and identifying long-term side effects such as antibiotic resistance or Clostridium difficile colitis.

PMID:28614043 | DOI:10.1089/sur.2017.073

Response to "Re-Thinking the Definition of Complicated Intra-Abdominal Infection"

Tue, 04/11/2017 - 05:00

Surg Infect (Larchmt). 2017 Apr;18(3):375-376. doi: 10.1089/sur.2017.057.


PMID:28394744 | DOI:10.1089/sur.2017.057

The Surgical Infection Society Revised Guidelines on the Management of Intra-Abdominal Infection

Sat, 01/14/2017 - 05:00

Surg Infect (Larchmt). 2017 Jan;18(1):1-76. doi: 10.1089/sur.2016.261.


BACKGROUND: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations.

METHODS: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council.

RESULTS: This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included.

SUMMARY: The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline.

PMID:28085573 | DOI:10.1089/sur.2016.261

Age and Its Impact on Outcomes with Intra-Abdominal Infection

Fri, 12/23/2016 - 05:00

Surg Infect (Larchmt). 2017 Feb/Mar;18(2):77-82. doi: 10.1089/sur.2016.184. Epub 2016 Dec 22.


BACKGROUND: Age has been shown to play a significant role in the etiology of complicated intra-abdominal infections (cIAIs), but the correlation between age and outcomes after therapy was not investigated in the Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial.

PATIENTS AND METHODS: Data were obtained by post hoc analysis of the STOP-IT trial database. Patients were stratified by age <65 or ≥65 years. Primary outcomes were surgical site infection (SSI), recurrent IAI (recIAI), and death. Multivariable analysis was performed to identify independent predictors of outcomes.

RESULTS: There were 398 subjects <65 and 120 ≥ 65 years. Overall baseline characteristics of the two groups were similar. The site of infection was similar between groups except: Colon or rectum (48.3% vs. 29.9%, p = 0.0002) and biliary tree (16.7% vs. 9.1%, p = 0.02), which were more common in the older group, whereas small intestine (6.7% vs. 16.3%, p = 0.008) and appendix (4.2% vs.17.1%, p = 0.0004) were more common in the younger group. Among the primary outcomes, only death was significantly different between the age groups and was more prevalent in the ≥65 years group (4 [3.3%] vs. 1 [0.3%], p = 0.01). Surgical site infection (9.2% vs. 7.3%, p = 0.50), recIAI (15.8% vs. 14.4%, p = 0.69), and a composite outcome (26.7% vs. 20.4%, p = 0.14) were statistically similar between the age groups, and this remained true when controlling for other co-variables. Multivariable analyses did not reveal age as an independent predictor of the composite or individual outcomes.

CONCLUSION: Patients with a more advanced age demonstrated variable sources of infection relative to the younger cohort, yet received similar treatments. Patient age was not an independent predictor of the undesired cIAI outcomes. These findings suggest that advanced age itself does not play a significant role in predicting these adverse outcomes for cIAIs and does not necessitate an altered treatment tactic.

PMID:28005468 | DOI:10.1089/sur.2016.184

Antimicrobial Stewardship: A Call to Action for Surgeons

Thu, 11/10/2016 - 05:00

Surg Infect (Larchmt). 2016 Dec;17(6):625-631. doi: 10.1089/sur.2016.187. Epub 2016 Nov 9.


Despite current antimicrobial stewardship programs (ASPs) being advocated by infectious disease specialists and discussed by national and international policy makers, ASPs coverage remains limited to only certain hospitals as well as specific service lines within hospitals. The ASPs incorporate a variety of strategies to optimize antimicrobial agent use in the hospital, yet the exact set of interventions essential to ASP success remains unknown. Promotion of ASPs across clinical practice is crucial to their success to ensure standardization of antimicrobial agent use within an institution. To effectively accomplish this standardization, providers who actively engage in antimicrobial agent prescribing should participate in the establishment and support of these programs. Hence, surgeons need to play a major role in these collaborations. Surgeons must be aware that judicious antibiotic utilization is an integral part of any stewardship program and necessary to maximize clinical cure and minimize emergence of antimicrobial resistance. The battle against antibiotic resistance should be fought by all healthcare professionals. If surgeons around the world participate in this global fight and demonstrate awareness of the major problem of antimicrobial resistance, they will be pivotal leaders. If surgeons fail to actively engage and use antibiotics judiciously, they will find themselves deprived of the autonomy to treat their patients.

PMID:27828764 | PMC:PMC5124748 | DOI:10.1089/sur.2016.187

Prophylactic Gentamicin Is Not Associated with Acute Kidney Injury in Patients with Open Fractures

Tue, 08/09/2016 - 05:00

Surg Infect (Larchmt). 2016 Dec;17(6):720-723. doi: 10.1089/sur.2015.086. Epub 2016 Aug 8.


BACKGROUND: Data on antimicrobial prophylaxis for open fractures is limited, with many protocols based on expert recommendations. These protocols include aminoglycosides (AGs) for fractures with significant soft tissue injury, but these drugs are associated with acute kidney injury (AKI) in other settings; this risk has not been defined for open fracture prophylaxis.

METHODS: We performed a retrospective study from May 2012 to October 2014 at our Level 1 trauma center. Patients with open fractures were evaluated for demographics, location/type of fracture, injury severity, and receipt of an AG. Outcomes included rates of AKI, infection, and mortality.

RESULTS: There were 167 patients with open fractures during the study period (119 males, mean age 42 ± 17 [standard deviation] years), with 80 (48%) receiving prophylactic gentamicin (AG+ group). The AG+ and AG- patients had similar fracture sites and Injury Severity Scores (ISSs) (12.6 ± 9.9 AG+ vs. 15.9 ± 13.2 AG-) but were more likely to have sustained blunt trauma (96% AG+ vs. 77%; p < 0.001) or received intravenous contrast medium ≤48 h from admission (75% AG+ vs. 56% AG-; p = 0.01). Gentamicin was not associated with AKI (odds ratio [OR] 0.22; 95% confidence interval [CI] 0.020-2.44; p = 0.22), whereas hypotension on admission (OR 10.7; 95% CI 1.42-80.93; p = 0.02) and ISS (OR 1.1; 95% CI 1.01-1.20; p = 0.02) were both associated with AKI. Only four fracture site infections were identified, three in the AG+ group and one in the AG- group (3.8% vs. 1.1%; p = 0.27). The mortality rate was greater in the AG- group (3.8% vs. 12.6%; p = 0.04).

CONCLUSIONS: Prophylactic gentamicin is not associated with AKI, whereas hypotension on admission and higher ISS were. The use of nephrotoxic agents, including aminoglycosides, should be restricted in open fracture patients presenting with hypotension or a high ISS.

PMID:27500970 | DOI:10.1089/sur.2015.086

Inclusion of Vancomycin as Part of Broad-Spectrum Coverage Does Not Improve Outcomes in Patients with Intra-Abdominal Infections: A Post Hoc Analysis

Wed, 08/03/2016 - 05:00

Surg Infect (Larchmt). 2016 Dec;17(6):694-699. doi: 10.1089/sur.2016.095. Epub 2016 Aug 2.


BACKGROUND: Management of complicated intra-abdominal infections (cIAIs) includes broad-spectrum antimicrobial coverage and commonly includes vancomycin for the empiric coverage of methicillin-resistant Staphylococcus aureus (MRSA). Ideally, culture-guided de-escalation follows to promote robust antimicrobial stewardship. This study assessed the impact and necessity of vancomycin in cIAI treatment regimens.

PATIENTS AND METHODS: A post hoc analysis of the Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial was performed. Patients receiving piperacillin-tazobactam (P/T) and/or a carbapenem were included with categorization based on use of vancomycin. Univariate and multivariable analyses evaluated effects of including vancomycin on individual and the composite of undesirable outcomes (recurrent IAI, surgical site infection [SSI], or death).

RESULTS: The study cohort included 344 patients with 110 (32%) patients receiving vancomycin. Isolation of MRSA occurred in only eight (2.3%) patients. Vancomycin use was associated with a similar composite outcome, 29.1%, vs. no vancomycin, 22.2% (p = 0.17). Patients receiving vancomycin had (mean [standard deviation]) higher Acute Physiology and Chronic Health Evaluation II scores (13.1 [6.6] vs. 9.4 [5.7], p < 0.0001), extended length of stay (12.6 [10.2] vs. 8.6 [8.0] d, p < 0.001), and prolonged antibiotic courses (9.1 [8.0] vs. 7.1 [4.9] d, p = 0.02). After risk adjustment in a multivariate model, no significant difference existed for the measured outcomes.

CONCLUSIONS: This post hoc analysis reveals that addition of vancomycin occurred in nearly one third of patients and more often in sicker patients. Despite this selection bias, no appreciable differences in undesired outcomes were demonstrated, suggesting limited utility for adding vancomycin to cIAI treatment regimens.

PMID:27483362 | DOI:10.1089/sur.2016.095

Infections in the Non-Transplanted Immunocompromised Host

Sat, 05/21/2016 - 05:00

Surg Infect (Larchmt). 2016 Jun;17(3):323-8. doi: 10.1089/sur.2016.008.


BACKGROUND: Discoveries regarding the basic mechanisms underlying malignant disease, rheumatologic disorders, and autoimmune diseases have led to the development of many new therapeutic modalities that target components of the immune system. Most of these are antibodies or fusion proteins that interfere with components of the immune response that are playing both pathological and protective roles, resulting in variable degrees of immune suppression and a higher risk of infectious complications.

METHODS: Review of the English-language literature.

RESULTS: As these modalities are often used in combination with more traditional methods of immune suppression (e.g., corticosteroids), an increasing spectrum of infection is being encountered by clinicians. Febrile neutropenia requires rapid assessment and initiation of empiric broad-spectrum antimicrobial therapy. Persistence despite this therapy should prompt further investigation for drug-resistant bacteria and invasive fungal disease. Important pathogens to consider in patients with neutropenia, chronic steroid exposure, or underlying gastrointestinal malignant diseases include fungi (Candida, Aspergillus) and atypical bacteria (Nocardia, Clostridium septicum).

CONCLUSIONS: This review focuses on observations regarding the greater risk of infections associated with many of these new biological modalities, as well as some specific infectious complications that may be encountered more commonly by the surgical consultant.

PMID:27206239 | DOI:10.1089/sur.2016.008

Understanding Gram-negative Central Line-Associated Blood Stream Infection in a Surgical Trauma ICU

Wed, 07/29/2015 - 05:00

Am Surg. 2015 Aug;81(8):816-9.


The purpose of this study was to review central line-associated blood stream infection (CLABSI) data from a surgical trauma intensive care unit to better understand patient risk factors, pathogens, and treatment interventions. We performed a retrospective review of all surgical ICU patients who met the Centers for Disease Control definition for Gram-negative CLABSI from 2006 through 2013. Demographics, pathogens, interventions, and outcomes were evaluated. A total of 40 patients were included with an average age of 49.9 ± 19 years and 72.5 per cent male. The average length of central venous line (CVL) was 11 ± 5.9 days with average time from line placement to positive culture 9.4 ± 6.8 days. Most common organisms were Enterobacter species (37.5%) with 17.8 per cent of all cultured organisms considered multidrug resistant. Piperacillin-tazobactam (67.5%) was the most commonly used antibiotic. Overall mortality rate was 22.5 per cent. A total of 11 patients who developed a recurrence did so at 10.7 ± 8 days and were similar to those without recurrence. Predominant pathogens associated with surgical trauma intensive care unit CLABSI in this study are different from those Gram-negative bacteria associated with published studies in the general hospital population. Further investigation into risk factors for infection and relapse is important to minimize such consequences. Understanding appropriate line placement and use as well as clarifying optimal duration of therapy is integral in improving outcomes.


Thrombocytopenia Associated with Linezolid Therapy in Solid Organ Transplant Recipients: A Retrospective Cohort Study

Sat, 07/25/2015 - 05:00

Surg Infect (Larchmt). 2015 Aug;16(4):361-7. doi: 10.1089/sur.2013.190. Epub 2015 May 28.


BACKGROUND: Linezolid is associated infrequently with bone marrow suppression in immunocompetent patients, but hematologic complications from linezolid in transplant recipients are understudied. This study evaluated the hematologic safety of linezolid in solid organ transplant recipients.

METHODS: We performed a retrospective study of inpatients at our institution treated with linezolid from June 1, 2009 until June 6, 2012. The solid organ transplant cohort (TP) was compared with the non-transplant cohort (NTP) using parameters related to linezolid safety. Outcomes included incidences of leukopenia or thrombocytopenia at the end of linezolid treatment (EOT), lengths of stay, and blood product requirements.

RESULTS: The TP cohort included 110 patients; the NTP cohort included 583 patients. Baseline parameters were similar between the TP and NTP cohorts. Non-transplant patients were more likely to have methicillin-resistant Staphylococcus aureus (MRSA), whereas TP patients received more doses of linezolid (17.0 vs. 11.3, p<0.001) and were more likely to receive other drugs associated with thrombocytopenia (91.7% vs. 11.3%, p<0.0001). Transplant patients with normal platelet counts at baseline were more likely to have EOT thrombocytopenia (29.3% vs. 10.7%, p=0.005), and multivariable regression analysis confirmed only a beginning platelet count less than 150,000 platelets per micoliter to be significantly different between groups: 43% TP versus 26.9% NTP (p=0.0009) making it the only independent predictor of EOT thrombocytopenia. Finally, TP patients were more likely to require platelet transfusions compared with the NTP cohort.

CONCLUSIONS: Transplant patients who received linezolid had a higher incidence of EOT thrombocytopenia and platelet transfusions, compared with NTP. Transplant patients who are thrombocytopenic at baseline are at the greatest risk. These findings may relate to more frequent use of drugs associated with marrow suppression or greater linezolid exposure in the TP cohort. Clinicians caring for transplant patients should take into account this higher risk of thrombocytopenia and need for platelets when considering use of linezolid in this population.

PMID:26207396 | DOI:10.1089/sur.2013.190