Antifungal Resistance Patterns in Molds Isolated from Wounds of Combat-Related Trauma Patients

Abstract Background An outbreak of trauma-related invasive fungal infections (IFI) occurred in US service members injured in Afghanistan. Empiric treatment included voriconazole (VORI) and amphotericin (AMB) and aggressive surgical debridement. Antifungal susceptibilities (AS) and relation to outcomes are yet to be described. Methods Between 2009 and 2013, military trauma patients with initial unique and serial (>3 days after initial isolation) molds isolated from wounds and admitted to Brooke Army Medical Center as part of the Trauma Infectious Disease Outcomes Study were assessed. The AS to AMB, VORI, posaconazole (POSA), isavuconazole (ISA), itraconazole, and caspofungin were determined by broth microdilution with CLSI breakpoint interpretations for Aspergillus spp. and mucormycetes (MM). Results Included are 18 patients with 28 initial mold isolates with 72% of IFI diagnosed via histopathology. All patients were male with a median of eight operations. There was a median of 11 days post-injury to mold culture. Initial isolates were five Aspergillus spp., three MM, three Fusarium spp., and combinations of three Aspergillus and MM, two Aspergillus and Fusarium, one Aspergillus and Bipolaris, one MM and Fusarium. A. flavus (AFL) and A. fumigatus (AFU) were all susceptible to AMB and POSA and 25% of AFL were intermediate to VORI. Four A. terreus (AT) isolates had MICs to AMB of 0.25, 1, 2, and 4, and were susceptible to VORI. ISA MIC50 and 90 were one and two for Aspergillus spp. Fusarium spp. MICs were >16 for VORI, POSA, and ISA, with AMB MIC50/90 of two and three. Among MM isolates, 86% were susceptible to AMB and 29% to POSA, and ISA MIC50 and MIC90 were 8 and >16. Five patients had serial isolates. One with serial AFL and AFU received no antifungal therapy, one with AT was treated with VORI, AMB, and POSA, and one with AFL was treated with AMB with no new resistance. The patient with serial MM was treated with AMB and VORI and remained resistant to POSA, but susceptible to AMB. Serial A. elegans acquired new POSA and AMB resistance and ISA MIC increased from 4 to 16 after AMB and VORI exposure. Conclusion Antifungal exposure to AMB and VORI was not associated with new resistance within Aspergillus spp., but 50% of MM exposed to this combination developed POSA and AMB resistance. Despite resistance of Fusarium, it was not isolated on subsequent debridements. Disclosures All authors: No reported disclosures.

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1184. Resistance Patterns and Susceptibility Analysis of Klebsiella pneumoniae Infections in Service Members Who Sustained Trauma in Iraq and Afghanistan

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.1017 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S357-S358

Author(s):

John Kiley ◽

Katrin Mende ◽

Susan J Kaiser ◽

Leigh Carson ◽

Dan Z Lu ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Common Species ◽

Multidrug Resistant ◽

Trauma Patients ◽

Disease Outcomes ◽

Antibiotic Susceptibilities ◽

Military Trauma ◽

Resistance Patterns ◽

Outcomes Study ◽

Susceptibility And Resistance

Abstract Background Klebsiella pneumoniae was the third most common species of multidrug-resistant (MDR) Gram-negative organism in military trauma patients injured in Iraq and Afghanistan (2009–2014). This study aims to characterize the antimicrobial susceptibility and resistance patterns of K. pneumoniae isolates in these patients. Methods All infecting K. pneumoniae isolates (IKpI) archived by the Trauma Infectious Disease Outcomes Study (TIDOS) and 96 colonizing isolates (CKpI) from groin swabs were included (6/09-12/14). All CKpI linked with IKpI were included; the remainder to total 50 MDR and 46 non-MDR CKpI were chosen randomly. Antimicrobial identification and susceptibilities were determined by CLSI criteria using the BD Phoenix Automated Microbiology System. MDR was defined as either resistance to ≥3 classes of aminoglycosides, β-lactams, carbapenems, and/or fluoroquinolones or production of an ESBL or KPC. Results Of 588 K. pneumoniae archived isolates, 237 isolates were included in the analysis (141 IKpI and 96 CKpI). IKpI sources were 40% wound, 22% respiratory, 20% blood, 9% urine, and 9% other. Antibiotic susceptibilities for IKpI were: cefazolin (CFZ) 20%, ceftriaxone 30%, levofloxacin 62%, piperacillin–tazobactam (PTZ) 41%, meropenem 96%, and amikacin 89%. MDR IKpI and CKpI were more likely to have had prior fluoroquinolone (82% vs. 18%, P < 0.01) or anti-pseudomonal penicillin (53% vs. 47%, P < 0.01) exposure. Seventeen patients had CKpI cultured at a median of 5 days (IQR 2–17) before a subsequent IKpI with 11 (65%) having MDR CKpI. All IKpI isolated after MDR CKpI were also MDR. Among IKpI recovered after non-MDR CKpI, new resistance was noted in 1 IKpI to gentamicin (200 days post-CKpI), 1 IKpI to ertapenem (7 days post-CKpI), two IKpI to CFZ (10 days and 17 days, respectively), and 1 IKpI to PTZ (19 days post-CKpI). Serial isolates of IKpI had similar MDR status (63% initial IKpI were MDR, whereas 76% of subsequent IKpI were MDR). Conclusion K. pneumoniae isolates in military trauma patients from Iraq and Afghanistan had challenging resistance patterns. Prior exposure to fluoroquinolones and anti-pseudomonal penicillins were associated with MDR K. pneumoniae isolation. MDR status of CKpI predicted subsequent IKpI MDR status. Disclosures All authors: No reported disclosures.

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Resistance patterns and clinical outcomes of Klebsiella pneumoniae and invasive Klebsiella variicola in trauma patients

PLoS ONE ◽

10.1371/journal.pone.0255636 ◽

2021 ◽

Vol 16 (8) ◽

pp. e0255636

Author(s):

John L. Kiley ◽

Katrin Mende ◽

Miriam L. Beckius ◽

Susan J. Kaiser ◽

M. Leigh Carson ◽

...

Keyword(s):

Bloodstream Infections ◽

Multidrug Resistant ◽

Trauma Patients ◽

Blast Injuries ◽

Chain Reaction ◽

Disease Outcomes ◽

String Test ◽

Resistance Patterns ◽

Outcomes Study ◽

Polymerase Chain

Recent reclassification of the Klebsiella genus to include Klebsiella variicola, and its association with bacteremia and mortality, has raised concerns. We examined Klebsiella spp. infections among battlefield trauma patients, including occurrence of invasive K. variicola disease. Klebsiella isolates collected from 51 wounded military personnel (2009–2014) through the Trauma Infectious Disease Outcomes Study were examined using polymerase chain reaction (PCR) and pulsed-field gel electrophoresis. K. variicola isolates were evaluated for hypermucoviscosity phenotype by the string test. Patients were severely injured, largely from blast injuries, and all received antibiotics prior to Klebsiella isolation. Multidrug-resistant Klebsiella isolates were identified in 23 (45%) patients; however, there were no significant differences when patients with and without multidrug-resistant Klebsiella were compared. A total of 237 isolates initially identified as K. pneumoniae were analyzed, with 141 clinical isolates associated with infections (remaining were colonizing isolates collected through surveillance groin swabs). Using PCR sequencing, 221 (93%) isolates were confirmed as K. pneumoniae, 10 (4%) were K. variicola, and 6 (3%) were K. quasipneumoniae. Five K. variicola isolates were associated with infections. Compared to K. pneumoniae, infecting K. variicola isolates were more likely to be from blood (4/5 versus 24/134, p = 0.04), and less likely to be multidrug-resistant (0/5 versus 99/134, p<0.01). No K. variicola isolates demonstrated the hypermucoviscosity phenotype. Although K. variicola isolates were frequently isolated from bloodstream infections, they were less likely to be multidrug-resistant. Further work is needed to facilitate diagnosis of K. variicola and clarify its clinical significance in larger prospective studies.

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502. Klebsiella variicola Infections in Service Members Who Sustained Trauma in Iraq and Afghanistan

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.571 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S243-S244

Author(s):

John L Kiley ◽

Katrin Mende ◽

Miriam Beckius ◽

Susan Kaiser ◽

M Leigh Carson ◽

...

Keyword(s):

Injury Severity ◽

Length Of Hospital Stay ◽

Patient Characteristics ◽

Invasive Disease ◽

Multidrug Resistant ◽

Trauma Patients ◽

Disease Outcomes ◽

Military Trauma ◽

Pcr Targeting ◽

Selection Of

Abstract Background Recent work has argued that genus Klebsiella is best divided into 3 clades: K. pneumoniae (Kp), K. quasipneumoniae (Kq), and K. variicola (Kv). Kv has drawn attention from reports of higher mortality and virulence. We evaluated a previously defined group of military trauma patients with Klebsiella infections for the presence of Kv, described clinical and isolate characteristics, and compared Kv and Kp groups. Methods All initial and serial (≥7 days from prior isolate) infecting Kp isolates (identified by clinical laboratories without the ability to speciate Kq and Kv) were collected from the Trauma Infectious Disease Outcomes Study (6/09–12/14). Additionally, a previously defined group of colonizing isolates linked to the infecting isolates and a selection of random colonizers were included from groin swabs. DNA extraction and PCR targeting Kv per published methods was performed. Antimicrobial susceptibilities were determined using the BD Phoenix Automated Microbiology System and CLSI criteria. Multidrug resistance was defined as either resistance to ≥3 classes of aminoglycosides, β-lactams, carbapenems and/or fluoroquinolones or production of ESBL or KPC. Results Of 237 archived Kp isolates (from 122 patients), 10 (4%) were identified as Kv by PCR (from 8 [7%] patients). The Kv sources were 4 from blood (40%), 1 intra-abdominal (10%) and 5 from groin (50%). Six (3%) isolates were identified as Kq (4 from groin and 2 from respiratory specimens). The Kv and Kp patients were all males, with a median age of 25 (IQR 21–46) and 23 (IQR 21–28), length of hospital stay of 24 days (IQR: 5–106) and 53 days (IQR 36–74), and Injury Severity Score of 21 (IQR: 10–50) and 38 (IQR: 30–45), respectively. There were no deaths in the Kv group compared with 4 with Kp. Infecting Kv isolates were more likely to be from blood compared with Kp (80% vs. 17%, P = 0.04). No infecting Kv isolates were multidrug-resistant compared with 70% of infecting Kp isolates (P < 0.01). Conclusion Kv represented 4% of the previously identified Kp isolates in this population. Patient characteristics were similar in both groups. While Kv was less resistant than Kp, it was more likely to be associated with invasive disease in this group. Disclosures All authors: No reported disclosures.

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The Causative Organisms of Bacterial Meningitis and their Antimicrobial Resistance Profiles in Iranian Children in 2011-2016

Infectious Disorders - Drug Targets ◽

10.2174/1871526519666181123130101 ◽

2020 ◽

Vol 20 (2) ◽

pp. 229-236

Author(s):

Sepideh Keshavarz Valian ◽

Shima Mahmoudi ◽

Babak Pourakbari ◽

Maryam Banar ◽

Mohammad Taghi Haghi Ashtiani ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Bacterial Meningitis ◽

Medical Center ◽

Blood Cultures ◽

Gram Positive ◽

Gram Negative ◽

Number Of Patients ◽

Resistance Patterns ◽

Iranian Children ◽

Surgery Department

Objective: The study aimed to describe the identity and antimicrobial resistance patterns of the causative agents of bacterial meningitis in children referred to Children’s Medical Center (CMC) Hospital, Tehran, Iran. Methods: This retrospective study was performed at CMC Hospital during a six-year period from 2011 to 2016. The microbiological information of the patients with a diagnosis of bacterial meningitis was collected and the following data were obtained: patients’ age, sex, hospital ward, the results of CSF and blood cultures, and antibiotic susceptibility profiles of isolated organisms. Results: A total of 118 patients with bacterial meningitis were admitted to CMC hospital. Sixty-two percent (n=73) of the patients were male. The median age of the patients was ten months (interquartile range [IQR]: 2 months-2 years) and the majority of them (n=92, 80%) were younger than two years of age. The highest number of patients (n=47, 40%) were admitted to the surgery department. Streptococcus epidermidis was the most frequent isolated bacterium (n=27/127, 21%), followed by Klebsiella pneumoniae (n=20/127, 16%), and Staphylococcus aureus (n=16/127, 12.5%). Blood culture was positive in 28% (n=33/118) of patients. Ampicillin-sulbactam and imipenem were the most effective antibiotics against Gram-negative bacteria isolated from CSF cultures. In the case of Gram-positive organisms, ampicillinsulbactam, vancomycin, and linezolid were the best choices. Imipenem was the most active drug against Gram-negative blood pathogens. Also, ampicillin and vancomycin had the best effect on Gram-positive bacteria isolated from blood cultures. Conclusion: Results of this study provide valuable information about the antibiotic resistance profiles of the etiologic agents of childhood meningitis, which can be used for prescription of more effective empirical therapies.

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Infectious Complications of Noncombat Trauma Patients Provided Care at a Military Trauma Center

Military Medicine ◽

10.7205/milmed-d-09-00098 ◽

2010 ◽

Vol 175 (5) ◽

pp. 317-323 ◽

Cited By ~ 8

Author(s):

Heather C. Yun ◽

Lorne H. Blackbourne ◽

John A. Jones ◽

John B. Holcomb ◽

Duane R. Hospenthal ◽

...

Keyword(s):

Trauma Center ◽

Infectious Complications ◽

Trauma Patients ◽

Military Trauma

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Candida parapsilosis Candidemia Resistance Patterns and Treatment Outcomes: An Opportunity for Antifungal Stewardship

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.037 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S86-S86

Author(s):

Gary Fong ◽

Kim Ngo ◽

Hannah Russo ◽

Nicholas Beyda

Keyword(s):

Combination Therapy ◽

Treatment Outcomes ◽

Candida Parapsilosis ◽

Medical Center ◽

Antifungal Susceptibility ◽

Antifungal Stewardship ◽

Resistance Patterns ◽

Fluconazole Therapy ◽

The Impact ◽

Research Grant

Abstract Background Candida parapsilosis has emerged as an important fungal pathogen with mortality rates up to 30%. Recent studies show no difference in treatment outcomes for patients treated both empirically and definitively with either echinocandins or fluconazole. However, the impact of antifungal susceptibility testing and opportunities for antifungal stewardship are less clear in this patient population. The purpose of this study was to assess antifungal susceptibility rates, treatment patterns, and outcomes among patients with C. parapsilosis candidemia. Methods This was a single-center, retrospective cohort review of adult patients with a positive blood culture for C. parapsilosis hospitalized at Baylor St. Luke’s Medical Center, between 2006 and 2016. Patients with mixed or breakthrough candidemia were excluded as well as patients who expired within 3 days of candidemia onset. Results Eighty patients with C. parapsilosis candidemia were identified of which 48 met inclusion criteria. Nine patients had infections caused by fluconazole non-susceptible isolates (19%). The most common empiric treatment choice was an echinocandin (33/48, 69%), followed by fluconazole (9/48, 19%), and combination therapy (6/48, 13%). Of the 39 patients with fluconazole susceptible isolates, only 17 were treated with fluconazole definitively (44%). Among patients who received empiric echinocandin vs. fluconazole therapy, there was no difference in 14-day mortality (9% vs. 11%, P = 1.00) or in-hospital mortality (12% vs. 11%, P = 1.00). Empiric combination therapy was the only independent risk factor for treatment failure (OR, 13.8; 95% CI, 1.4–138.3; P = 0.03). Conclusion Treatment outcomes for patients receiving echinocandins were similar for those receiving fluconazole. At our institution, the increased incidence of fluconazole non-susceptible isolates warrants the use of echinocandins empirically. Patients were more likely to remain on echinocandin therapy even when fluconazole susceptible isolates were identified. This study reinforces the guideline suggestion that neither echinocandins nor fluconazole treatment leads to superior outcomes, but also identifies a cohort of patients in need of antifungal stewardship. Disclosures N. Beyda, Astellas: Grant Investigator and Scientific Advisor, Research grant

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1405Antimicrobial Susceptibility of Obligate Anaerobes Isolated from Military Trauma Patients

Open Forum Infectious Diseases ◽

10.1093/ofid/ofu052.951 ◽

2014 ◽

Vol 1 (suppl_1) ◽

pp. S370-S370

Author(s):

Brian White ◽

Katrin Mende ◽

Amy Weintrob ◽

Miriam Beckius ◽

Wendy Zera ◽

...

Keyword(s):

Trauma Patients ◽

Military Trauma

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Anastomotic Outcomes in Military Exploratory Laparotomies in the Modern Combat Era

The American Surgeon ◽

10.1177/00031348211050281 ◽

2022 ◽

pp. 000313482110502

Author(s):

Patrick F. Walker ◽

Joseph D. Bozzay ◽

David W. Schechtman ◽

Faraz Shaikh ◽

Laveta Stewart ◽

...

Keyword(s):

Medical Center ◽

Damage Control ◽

Surgical Site Infections ◽

Trauma Patients ◽

Intestinal Anastomoses ◽

Military Hospitals ◽

Anastomotic Failure ◽

Significant Difference ◽

Regional Medical Center ◽

Outcome Differences

Background Intestinal anastomoses in military settings are performed in severely injured patients who often undergo damage control laparotomy in austere environments. We describe anastomotic outcomes of patients from recent wars. Methods Military personnel with combat-related intra-abdominal injuries (June 2009-December 2014) requiring laparotomy with resection and anastomosis were analyzed. Patients were evacuated from Iraq or Afghanistan to Landstuhl Regional Medical Center (Germany) before being transferred to participating U.S. military hospitals. Results Among 341 patients who underwent 1053 laparotomies, 87 (25.5%) required ≥1 anastomosis. Stapled anastomosis only was performed in 57.5% of patients, while hand-sewn only was performed in 14.9%, and 9.2% had both stapled and hand-sewn techniques (type unknown for 18.4%). Anastomotic failure occurred in 15% of patients. Those with anastomotic failure required more anastomoses (median 2 anastomoses, interquartile range [IQR] 1-3 vs. 1 anastomosis, IQR 1-2, P = .03) and more total laparotomies (median 5 laparotomies, IQR 3-12 vs. 3, IQR 2-4, P = .01). There were no leaks in patients that had only hand-sewn anastomoses, though a significant difference was not seen with those who had stapled anastomoses. While there was an increasing trend regarding surgical site infections (SSIs) with anastomotic failure after excluding superficial SSIs, it was not significant. There was no difference in mortality. Discussion Military trauma patients have a similar anastomotic failure rate to civilian trauma patients. Patients with anastomotic failure were more likely to have had more anastomoses and more total laparotomies. No definitive conclusions can be drawn about anastomotic outcome differences between hand-sewn and stapled techniques.

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Fusarium infection–induced partial failure of free anterolateral thigh musculocutaneous flap: Case report

SAGE Open Medical Case Reports ◽

10.1177/2050313x19841963 ◽

2019 ◽

Vol 7 ◽

pp. 2050313X1984196

Author(s):

Hsin-Han Chen ◽

Pin-Keng Shih

Keyword(s):

Late Onset ◽

Fungal Infections ◽

Fusarium Species ◽

Antifungal Drugs ◽

Musculocutaneous Flap ◽

Split Thickness Skin Graft ◽

Fusarium Spp ◽

Partial Failure ◽

Flap Failure ◽

Anterolateral Thigh

Fusarium species, a soil-borne fungi, causes disease in animals and humans, particularly in immunocompromized patients. A 62-year-old male presented with type II diabetes mellitus, diagnosed 4 years ago. He had a motorcycle accident-caused open tibiofibular fracture of the left lower extremity (Gustilo grade IIIb). With open reduction and internal fixation, an anterolateral thigh musculocutaneous flap was harvested for coverage of exposed bone and defect reconstruction. Partial failure of the flap occurred 9 days following reconstruction, and histological examination revealed Fusarium spp. After treatment with antifungal drugs and debridement, we performed a split-thickness skin graft. At 2-year follow-up, the flap was viable with adequate bone union. This is the first reported case of partial flap failure due to a Fusarium spp. infection. Possibility of fungal infections in patients with late-onset flap failure should be noted. Prompt diagnosis and treatment are needed to prevent repeated free-tissue transfer and/or devastating outcomes.

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The Impact of In-house Attending Surgeon Supervision on the Rates of Preventable and Potentially Preventable Complications and Death at the Start of the New Academic Year

The American Surgeon ◽

10.1177/000313481307901113 ◽

2013 ◽

Vol 79 (11) ◽

pp. 1134-1139 ◽

Cited By ~ 4

Author(s):

Kenji Inaba ◽

Adam Hauch ◽

Bernardino C. Branco ◽

Stephen Cohn ◽

Pedro G. R. Teixeira ◽

...

Keyword(s):

Los Angeles ◽

Trauma Center ◽

Medical Center ◽

Trauma Patients ◽

University Of Southern California ◽

Academic Level ◽

Significant Difference ◽

Level I ◽

The Impact ◽

Academic Year

The purpose of this study was to examine the impact of in-house attending surgeon supervision on the rate of preventable deaths (PD) and complications (PC) at the beginning of the academic year. All trauma patients admitted to the Los Angeles County 1 University of Southern California Medical Center over an 8-year period ending in December 2009 were reviewed. Morbidity and mortality reports were used to extract all PD/PC. Patients admitted in the first 2 months (July/ August) of the academic year were compared with those admitted at the end of the year (May/June) for two distinct time periods: 2002 to 2006 (before in-house attending surgeon supervision) and 2007 to 2009 (after 24-hour/day in-house attending surgeon supervision). During 2002 to 2006, patients admitted at the beginning of the year had significantly higher rates of PC (1.1% for July/ August vs 0.6% for May/June; adjusted odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1 to 3.2; P < 0.001). There was no significant difference in mortality (6.5% for July/August vs 4.6% for May/ June; adjusted OR, 1.1; 95% CI,0.8 to 1.5; P = 0.179). During 2007 to 2009, after institution of 24-hour/day in-house attending surgeon supervision of fellows and housestaff, there was no significant difference in the rates of PC (0.7% for July/August vs 0.6% for May/June; OR, 1.1; 95% CI, 0.8 to 1.3; P = 0.870) or PD (4.6% for July/August vs 3.7% for May/June; OR, 1.3; 95% CI, 0.9 to 1.7; P = 0.250) seen at the beginning of the academic year. At an academic Level I trauma center, the institution of 24-hour/day in-house attending surgeon supervision significantly reduced the spike of preventable complications previously seen at the beginning of the academic year.

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