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1.
Antimicrob Agents Chemother ; 66(4): e0241421, 2022 04 19.
Article in English | MEDLINE | ID: mdl-35341315

ABSTRACT

Klebsiella pneumoniae carbapenemases (KPC-2 and KPC-3) present a global clinical threat, as these ß-lactamases confer resistance to carbapenems and oxyimino-cephalosporins. Recent clinically identified KPC variants with substitutions at Ambler position D179, located in the Ω loop, are resistant to the ß-lactam/ß-lactamase inhibitor combination ceftazidime-avibactam, but susceptible to meropenem-vaborbactam. To gain insights into ceftazidime-avibactam resistance conferred by D179N/Y variants of KPC-2, crystal structures of these variants were determined. The D179N KPC-2 structure revealed that the change of the carboxyl to an amide moiety at position 179 disrupted the salt bridge with R164 present in wild-type KPC-2. Additional interactions were disrupted in the Ω loop, causing a decrease in the melting temperature. Shifts originating from N179 were also transmitted toward the active site, including ∼1-Å shifts of the deacylation water and interacting residue N170. The structure of the D179Y KPC-2 ß-lactamase revealed more drastic changes, as this variant exhibited disorder of the Ω loop, with other flanking regions also being disordered. We postulate that the KPC-2 variants can accommodate ceftazidime because the Ω loop is displaced in D179Y or can be more readily displaced in D179N KPC-2. To understand why the ß-lactamase inhibitor vaborbactam is less affected by the D179 variants than avibactam, we determined the crystal structure of D179N KPC-2 in complex with vaborbactam, which revealed wild-type KPC-2-like vaborbactam-active site interactions. Overall, the structural results regarding KPC-2 D179 variants revealed various degrees of destabilization of the Ω loop that contribute to ceftazidime-avibactam resistance, possible substrate-assisted catalysis of ceftazidime, and meropenem and meropenem-vaborbactam susceptibility.


Subject(s)
Ceftazidime , beta-Lactamase Inhibitors , Anti-Bacterial Agents/pharmacology , Azabicyclo Compounds/pharmacology , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Ceftazidime/pharmacology , Drug Combinations , Klebsiella pneumoniae/genetics , Meropenem/pharmacology , Microbial Sensitivity Tests , beta-Lactamase Inhibitors/pharmacology , beta-Lactamases/genetics
2.
Antimicrob Agents Chemother ; 63(12)2019 09 09.
Article in English | MEDLINE | ID: mdl-31527035

ABSTRACT

The pharmacokinetics (PK) and dialytic clearance of isavuconazole in vitro and in 7 solid organ transplant patients undergoing continuous renal replacement therapy (CRRT) were evaluated. In vivo, mean (± SD) plasma PK parameters of isavuconazole were: C max 4.00±1.45 mg/L, C min 1.76±0.76 mg/L, t ½ 48.36±29.78 h, Vss 288.78±182.11 L, CLss 4.85±3.79 L/h, and AUC 54.01±20.98 mg ⋅ h/L. Transmembrane clearance represented just 0.7% of the total isavuconazole clearance. These data suggest that isavuconazole is not readily removed by CRRT and no dose adjustments are necessary.

3.
J Antimicrob Chemother ; 74(3): 633-638, 2019 03 01.
Article in English | MEDLINE | ID: mdl-30534964

ABSTRACT

OBJECTIVES: To ensure the accuracy of susceptibility testing methods for ceftazidime/avibactam. METHODS: The performances of the Etest (bioMérieux), 30/20 µg disc (Hardy diagnostics) and 10/4 µg disc (Mast Group) were evaluated against the reference broth microdilution (BMD) method for 102 clinically relevant Gram-negative organisms: 69 ceftazidime- and meropenem-resistant Klebsiella pneumoniae and 33 MDR non-K. pneumoniae. Essential and categorical agreement along with major and very major error rates were determined according to CLSI guidelines. RESULTS: A total of 78% of isolates were susceptible to ceftazidime/avibactam. None of the three methods met the defined equivalency threshold against all 102 organisms. The Etest performed the best, with categorical agreement of 95% and major errors of 6.3%. Against the 69 ceftazidime- and meropenem-resistant K. pneumoniae, only the Etest and the 10/4 µg disc met the equivalency threshold. None of the three methods met equivalency for the 33 MDR isolates. There were no very major errors observed in any analysis. These results were pooled with those from a previous study of 74 carbapenem-resistant Enterobacteriaceae and data from the ceftazidime/avibactam new drug application to define optimal 30/20 µg disc thresholds using the error-rate bound model-based approaches of the diffusion breakpoint estimation testing software. This analysis identified a susceptibility threshold of ≤19 mm as optimal. CONCLUSIONS: Our data indicate that the Etest is a suitable alternative to BMD for testing ceftazidime/avibactam against ceftazidime- and meropenem-resistant K. pneumoniae. The 30/20 µg discs overestimate resistance and may lead to the use of treatment regimens that are more toxic and less effective.


Subject(s)
Anti-Bacterial Agents/pharmacology , Azabicyclo Compounds/pharmacology , Ceftazidime/pharmacology , Gram-Negative Bacteria/drug effects , Microbial Sensitivity Tests/methods , beta-Lactamase Inhibitors/pharmacology , Drug Combinations , Gram-Negative Bacteria/isolation & purification , Gram-Negative Bacterial Infections/microbiology , Humans , beta-Lactam Resistance
4.
Article in English | MEDLINE | ID: mdl-27799206

ABSTRACT

Method-dependent Etest epidemiological cutoff values (ECVs) are not available for susceptibility testing of either Candida or Aspergillus species with amphotericin B or echinocandins. In addition, reference caspofungin MICs for Candida spp. are unreliable. Candida and Aspergillus species wild-type (WT) Etest MIC distributions (microorganisms in a species-drug combination with no detectable phenotypic resistance) were established for 4,341 Candida albicans, 113 C. dubliniensis, 1,683 C. glabrata species complex (SC), 709 C. krusei, 767 C. parapsilosis SC, 796 C. tropicalis, 1,637 Aspergillus fumigatus SC, 238 A. flavus SC, 321 A. niger SC, and 247 A. terreus SC isolates. Etest MICs from 15 laboratories (in Argentina, Europe, Mexico, South Africa, and the United States) were pooled to establish Etest ECVs. Anidulafungin, caspofungin, micafungin, and amphotericin B ECVs (in micrograms per milliliter) encompassing ≥97.5% of the statistically modeled population were 0.016, 0.5, 0.03, and 1 for C. albicans; 0.03, 1, 0.03, and 2 for C. glabrata SC; 0.06, 1, 0.25, and 4 for C. krusei; 8, 4, 2, and 2 for C. parapsilosis SC; and 0.03, 1, 0.12, and 2 for C. tropicalis The amphotericin B ECV was 0.25 µg/ml for C. dubliniensis and 2, 8, 2, and 16 µg/ml for the complexes of A. fumigatus, A. flavus, A. niger, and A. terreus, respectively. While anidulafungin Etest ECVs classified 92% of the Candida fks mutants evaluated as non-WT, the performance was lower for caspofungin (75%) and micafungin (84%) cutoffs. Finally, although anidulafungin (as an echinocandin surrogate susceptibility marker) and amphotericin B ECVs should identify Candida and Aspergillus isolates with reduced susceptibility to these agents using the Etest, these ECVs will not categorize a fungal isolate as susceptible or resistant, as breakpoints do.


Subject(s)
Amphotericin B/pharmacology , Antifungal Agents/pharmacology , Aspergillus/drug effects , Candida/drug effects , Drug Resistance, Fungal , Echinocandins/pharmacology , Aspergillus/growth & development , Aspergillus/isolation & purification , Candida/growth & development , Candida/isolation & purification , Disk Diffusion Antimicrobial Tests , Europe , Latin America , South Africa , United States
5.
Osteoporos Int ; 27(3): 1149-1160, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26395887

ABSTRACT

SUMMARY: This study examined the effect of a controlled dose of vibration upon bone density and architecture in people with spinal cord injury (who eventually develop severe osteoporosis). Very sensitive computed tomography (CT) imaging revealed no effect of vibration after 12 months, but other doses of vibration may still be useful to test. INTRODUCTION: The purposes of this report were to determine the effect of a controlled dose of vibratory mechanical input upon individual trabecular bone regions in people with chronic spinal cord injury (SCI) and to examine the longitudinal bone architecture changes in both the acute and chronic state of SCI. METHODS: Participants with SCI received unilateral vibration of the constrained lower limb segment while sitting in a wheelchair (0.6g, 30 Hz, 20 min, three times weekly). The opposite limb served as a control. Bone mineral density (BMD) and trabecular micro-architecture were measured with high-resolution multi-detector CT. For comparison, one participant was studied from the acute (0.14 year) to the chronic state (2.7 years). RESULTS: Twelve months of vibration training did not yield adaptations of BMD or trabecular micro-architecture for the distal tibia or the distal femur. BMD and trabecular network length continued to decline at several distal femur sub-regions, contrary to previous reports suggesting a "steady state" of bone in chronic SCI. In the participant followed from acute to chronic SCI, BMD and architecture decline varied systematically across different anatomical segments of the tibia and femur. CONCLUSIONS: This study supports that vibration training, using this study's dose parameters, is not an effective anti-osteoporosis intervention for people with chronic SCI. Using a high-spatial-resolution CT methodology and segmental analysis, we illustrate novel longitudinal changes in bone that occur after spinal cord injury.


Subject(s)
Osteoporosis/prevention & control , Spinal Cord Injuries/complications , Vibration/therapeutic use , Adolescent , Adult , Bone Density/physiology , Cancellous Bone/diagnostic imaging , Child , Child, Preschool , Female , Femur/diagnostic imaging , Femur/physiopathology , Humans , Infant , Longitudinal Studies , Lower Extremity , Male , Osteoporosis/diagnostic imaging , Osteoporosis/etiology , Osteoporosis/physiopathology , Spinal Cord Injuries/physiopathology , Tibia/diagnostic imaging , Tibia/physiopathology , Tomography, X-Ray Computed/methods , Young Adult
6.
Am J Transplant ; 15(1): 180-9, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25359455

ABSTRACT

Guidelines recommend targeted antifungal prophylaxis for liver transplant (LT) recipients based on tiers of risk, rather than universal prophylaxis. The feasibility and efficacy of tiered, targeted prophylaxis is not well established. We performed a retrospective study of LT recipients who received targeted prophylaxis (n = 145; voriconazole [VORI; 54%], fluconazole [8%], no antifungal [38%]) versus universal VORI prophylaxis (n = 237). Median durations of targeted and universal prophylaxis were 11 and 6 days, respectively (p < 0.0001). The incidence of invasive fungal infections (IFIs) in targeted and universal groups was 6.9% and 4.2% (p = 0.34). Overall, intra-abdominal candidiasis (73%) was the most common IFI. Posttransplant bile leaks (p = 0.001) and living donor transplants (p = 0.04) were independent risk factors for IFI. IFIs occurred in 6% of high-risk transplants who received prophylaxis and 4% of low-risk transplants who did not receive prophylaxis (p = 1.0). Mortality rates (100 days) were 10% (targeted) and 7% (universal) (p = 0.26); attributable mortality due to IFI was 10%. Compliance with prophylaxis recommendations was 97%. Prophylaxis was discontinued for toxicity in 2% of patients. Targeted antifungal prophylaxis in LT recipients was feasible and safe, effectively prevented IFIs and reduced the number of patients exposed to antifungals. Bile leaks and living donor transplants should be considered high-risk indications for prophylaxis.


Subject(s)
Antifungal Agents/therapeutic use , Graft Rejection/epidemiology , Liver Diseases/complications , Liver Transplantation/adverse effects , Mycoses/prevention & control , Transplant Recipients , Adult , Aged , Algorithms , Female , Follow-Up Studies , Graft Rejection/microbiology , Graft Survival , Humans , Immunocompromised Host , Liver Diseases/microbiology , Liver Diseases/surgery , Male , Middle Aged , Mycoses/epidemiology , Mycoses/microbiology , Postoperative Complications , Prognosis , Retrospective Studies , Risk Factors , Tissue Donors , United States/epidemiology
7.
Eur J Clin Microbiol Infect Dis ; 33(6): 1053-61, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24500598

ABSTRACT

Our objective was to model the cost-effectiveness and economic value of routine peri-operative Staphylococcus aureus screening and decolonization of lung and heart-lung transplant recipients from hospital and third-party payer perspectives. We used clinical data from 596 lung and heart-lung transplant recipients to develop a model in TreeAge Pro 2009 (Williamsport, MA, USA). Sensitivity analyses varied S. aureus colonization rate (5-15 %), probability of infection if colonized (10-30 %), and decolonization efficacy (25-90 %). Data were collected from the Cardiothoracic Transplant Program at the University of Pittsburgh Medical Center. Consecutive lung and heart-lung transplant recipients from January 2006 to December 2010 were enrolled retrospectively. Baseline rates of S. aureus colonization, infection and decolonization efficacy were 9.6 %, 36.7 %, and 31.9 %, respectively. Screening and decolonization was economically dominant for all scenarios tested, providing more cost savings and health benefits than no screening. Savings per case averted (2012 $US) ranged from $73,567 to $133,157 (hospital perspective) and $10,748 to $16,723 (third party payer perspective), varying with the probability of colonization, infection, and decolonization efficacy. Using our clinical data, screening and decolonization led to cost savings per case averted of $240,602 (hospital perspective) and averted 6.7 S. aureus infections (4.3 MRSA and 2.4 MSSA); 89 patients needed to be screened to prevent one S. aureus infection. Our data support routine S. aureus screening and decolonization of lung and heart-lung transplant patients. The economic value of screening and decolonization was greater than in previous models of other surgical populations.


Subject(s)
Carrier State/diagnosis , Carrier State/drug therapy , Mass Screening/economics , Staphylococcal Infections/diagnosis , Staphylococcal Infections/drug therapy , Staphylococcus aureus/isolation & purification , Transplant Recipients , Academic Medical Centers , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cohort Studies , Computer Simulation , Cost-Benefit Analysis , Female , Heart Transplantation , Humans , Infant , Lung Transplantation , Male , Mass Screening/methods , Middle Aged , Pennsylvania , Retrospective Studies , Young Adult
8.
Transpl Infect Dis ; 16(4): 578-87, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24962102

ABSTRACT

BACKGROUND: Few studies of Scedosporium infections following solid organ transplantation have been performed in the era of induction immunosuppression and widespread antifungal prophylaxis. METHODS: We performed a single-center, retrospective study of transplant recipients from 2000 through 2010 who had a positive Scedosporium culture. RESULTS: Among 27 patients, 67% (n = 18) and 33% (n = 9) were infected with Scedosporium apiospermum and Scedosporium prolificans, respectively. A total of 67% received induction immunosuppression and 74% received prior antifungal therapy. Isolates were broadly resistant to antifungals. Of these patients, 59% (n = 16) were colonized by Scedosporium, and 41% (n = 11) had disease (scedosporiosis). No significant clinical differences were seen between species. Colonization occurred exclusively in the lungs of lung transplant recipients (LTR). Scedosporiosis followed lung transplantation in 55%, and other organ transplants (multivisceral [18%]; and heart, liver, small intestine [9% each]) in 45%. Scedosporiosis was preceded by colonization in 36%. Diseases included pneumonia (64%), mediastinitis (18%), and fungemia/disseminated infections (18%). The 6-month outcomes were death in 55%, progression in 18%, stability in 9%, and resolution in 18%. Patients who died had earlier onset scedosporiosis post transplant (median: 80.5 vs. 1388 days; P = 0.04), and were more likely to have mediastinitis or disseminated infections than pneumonia (100% vs. 29%; P = 0.06). The 3 patients who developed scedosporiosis >1 year post transplant survived. All patients who survived were treated with a voriconazole-containing regimen. CONCLUSIONS: LTR were most susceptible to Scedosporium colonization and scedosporiosis, particularly within the lungs. Death was common with scedosporiosis in the first year after all types of organ transplants, consistent with profound immunosuppression and antifungal resistance, but not encountered thereafter.


Subject(s)
Mycoses/etiology , Organ Transplantation/adverse effects , Scedosporium/isolation & purification , Adult , Antifungal Agents/pharmacology , Drug Resistance, Fungal , Female , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Male , Microbial Sensitivity Tests , Middle Aged , Mycoses/microbiology , Retrospective Studies , Scedosporium/drug effects , Voriconazole/therapeutic use
9.
Am J Transplant ; 13(8): 2137-45, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23710593

ABSTRACT

We conducted a retrospective study of deep surgical site infections (SSIs) among consecutive patients who underwent lung transplantation (LTx) at a single center from 2006 through 2010. Thirty-one patients (5%) developed SSIs at median 25 days after LTx. Empyema was most common (42%), followed by surgical wound infections (29%), mediastinitis (16%), sternal osteomyelitis (6%), and pericarditis (6%). Pathogens included Gram-positive bacteria (41%), Gram-negative bacteria (41%), fungi (10%) and Mycobacterium abscessus, Mycoplasma hominis and Lactobacillus sp. (one each). Twenty-three percent of SSIs were due to pathogens colonizing recipients' native lungs at time of LTx, suggesting surgical seeding as a source. Patient-related independent risk factors for SSIs were diabetes and prior cardiothoracic surgery; procedure-related independent risk factors were LTx from a female donor, prolonged ischemic time and number of perioperative red blood cell transfusions. Mediastinitis and sternal infections were not observed among patients undergoing minimally invasive LTx. SSIs were associated with 35% mortality at 1 year post-LTx. Lengths of stay and mortality in-hospital and at 6 months and 1 year were significantly greater for patients with SSIs other than empyema. In conclusion, deep SSIs were uncommon, but important complications in LTx recipients because of their diverse microbiology and association with increased mortality.


Subject(s)
Graft Rejection/mortality , Gram-Negative Bacterial Infections/epidemiology , Gram-Positive Bacterial Infections/epidemiology , Lung Diseases/complications , Lung Transplantation/adverse effects , Postoperative Complications , Surgical Wound Infection/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Graft Rejection/etiology , Gram-Negative Bacteria/pathogenicity , Gram-Negative Bacterial Infections/microbiology , Gram-Negative Bacterial Infections/mortality , Gram-Positive Bacteria/pathogenicity , Gram-Positive Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/mortality , Humans , Lung Diseases/mortality , Lung Diseases/surgery , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Surgical Wound Infection/etiology , Surgical Wound Infection/mortality , Survival Rate , United States/epidemiology , Young Adult
10.
Am J Transplant ; 13(10): 2619-33, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24011185

ABSTRACT

We conducted a retrospective study of 17 transplant recipients with carbapenem-resistant Klebsiella pneumoniae bacteremia, and described epidemiology, clinical characteristics and strain genotypes. Eighty-eight percent (15/17) of patients were liver or intestinal transplant recipients. Outcomes were death due to septic shock (18%), cure (24%) and persistent (>7 days) or recurrent bacteremia (29% each). Thirty- and 90-day mortality was 18% and 47%, respectively. Patients who were cured received at least one active antimicrobial agent and underwent source control interventions. Forty-one percent (7/17) of patients had intra-abdominal infections; all except one developed persistent/recurrent bacteremia despite drainage. Two patients tolerated persistent bacteremia for >300 days. All patients except one were infected with sequence type 258 (ST258), K. pneumoniae carbapenemase (KPC)-2-producing strains harboring a mutant ompK35 porin gene; the exception was infected with an ST37, KPC-3-producing strain. Seventy-one percent (12/17) of patients were infected with ST258 ompK36 mutant strains. In two patients, persistent bacteremia was caused by two strains with different ompK36 genotypes. Three ompK36 mutations were associated with significantly higher carbapenem minimum inhibitory concentrations than wild-type ompK36. Pulse-field gel electrophoresis identified a single ST258 lineage; serial strains from individual patients were indistinguishable. In conclusion, KPC-K. pneumoniae bacteremia exhibited highly diverse clinical courses following transplantation, and was caused by clonal ST258 strains with different ompK36 genotypes.


Subject(s)
Bacteremia/epidemiology , Carbapenems/pharmacology , Klebsiella Infections/epidemiology , Klebsiella pneumoniae/genetics , Organ Transplantation , beta-Lactam Resistance/genetics , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Bacteremia/microbiology , DNA, Bacterial/genetics , Female , Follow-Up Studies , Humans , Klebsiella Infections/microbiology , Klebsiella Infections/mortality , Klebsiella pneumoniae/isolation & purification , Male , Microbial Sensitivity Tests , Middle Aged , Polymerase Chain Reaction , Prognosis , Retrospective Studies , Risk Factors , Survival Rate
11.
Osteoporos Int ; 23(9): 2335-46, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22187008

ABSTRACT

UNLABELLED: People with spinal cord injury (SCI) lose bone and muscle integrity after their injury. Early doses of stress, applied through electrically induced muscle contractions, preserved bone density at high-risk sites. Appropriately prescribed stress early after the injury may be an important consideration to prevent bone loss after SCI. INTRODUCTION: Skeletal muscle force can deliver high compressive loads to bones of people with spinal cord injury (SCI). The effective osteogenic dose of load for the distal femur, a chief site of fracture, is unknown. The purpose of this study is to compare three doses of bone compressive loads at the distal femur in individuals with complete SCI who receive a novel stand training intervention. METHODS: Seven participants performed unilateral quadriceps stimulation in supported stance [150% body weight (BW) compressive load-"High Dose" while opposite leg received 40% BW-"Low Dose"]. Five participants stood passively without applying quadriceps electrical stimulation to either leg (40% BW load-"Low Dose"). Fifteen participants performed no standing (0% BW load-"Untrained") and 14 individuals without SCI provided normative data. Participants underwent bone mineral density (BMD) assessment between one and six times over a 3-year training protocol. RESULTS: BMD for the High Dose group significantly exceeded BMD for both the Low Dose and the Untrained groups (p < 0.05). No significant difference existed between the Low Dose and Untrained groups (p > 0.05), indicating that BMD for participants performing passive stance did not differ from individuals who performed no standing. High-resolution CT imaging of one High Dose participant revealed 86% higher BMD and 67% higher trabecular width in the High Dose limb. CONCLUSION: Over 3 years of training, 150% BW compressive load in upright stance significantly attenuated BMD decline when compared to passive standing or to no standing. High-resolution CT indicated that trabecular architecture was preserved by the 150% BW dose of load.


Subject(s)
Bone Density/physiology , Femur/physiology , Muscle Contraction/physiology , Quadriceps Muscle/physiology , Spinal Cord Injuries/therapy , Tibia/physiology , Adolescent , Adult , Cross-Sectional Studies , Electric Stimulation Therapy/methods , Female , Humans , Longitudinal Studies , Male , Middle Aged , Spinal Cord Injuries/physiopathology , Tomography, X-Ray Computed/methods , Treatment Outcome , Young Adult
12.
Osteoporos Int ; 21(6): 985-95, 2010 Jun.
Article in English | MEDLINE | ID: mdl-19707702

ABSTRACT

SUMMARY: Surveillance of femur metaphysis bone mineral density (BMD) decline after spinal cord injury (SCI) may be subject to slice placement error of 2.5%. Adaptations to anti-osteoporosis measures should exceed this potential source of error. Image analysis parameters likewise affect BMD output and should be selected strategically in longitudinal studies. INTRODUCTION: Understanding the longitudinal changes in bone mineral density (BMD) after spinal cord injury (SCI) is important when assessing new interventions. We determined the longitudinal effect of SCI on BMD of the femur metaphysis. To facilitate interpretation of longitudinal outcomes, we (1) determined the BMD difference associated with erroneous peripheral quantitative computed tomography (pQCT) slice placement, and (2) determined the effect of operator-selected pQCT peel algorithms on BMD. METHODS: pQCT images were obtained from the femur metaphysis (12% of length from distal end) of adult subjects with and without SCI. Slice placement errors were simulated at 3 mm intervals and were processed in two ways (threshold-based vs. concentric peel). RESULTS: BMD demonstrated a rapid decline over 2 years post-injury. BMD differences attributable to operator-selected peel methods were large (17.3% for subjects with SCI). CONCLUSIONS: Femur metaphysis BMD declines after SCI in a manner similar to other anatomic sites. Concentric (percentage-based) peel methods may be most appropriate when special sensitivity is required to detect BMD adaptations. Threshold-based methods may be more appropriate when asymmetric adaptations are observed.


Subject(s)
Bone Density/physiology , Femur/physiopathology , Spinal Cord Injuries/physiopathology , Adolescent , Adult , Bone Diseases, Metabolic/diagnostic imaging , Bone Diseases, Metabolic/etiology , Bone Diseases, Metabolic/physiopathology , Cross-Sectional Studies , Disease Progression , Female , Femur/diagnostic imaging , Humans , Image Processing, Computer-Assisted/methods , Longitudinal Studies , Male , Middle Aged , Spinal Cord Injuries/complications , Tomography, X-Ray Computed/methods , Young Adult
13.
Transpl Infect Dis ; 12(6): 555-60, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20626709

ABSTRACT

Both bacteremia and biliary cast syndrome are serious post-transplant complications in liver transplant recipients. In the setting of increasing drug resistance in the current era, management of infections caused by multidrug-resistant (MDR) bacteria has proven challenging. We present a case of a liver transplant recipient who developed biliary cast syndrome and intractable MDR Pseudomonas bacteremia that failed to resolve with conventional antimicrobial therapy and which was finally controlled by a novel combination regimen of colistimethate, doripenem, and tobramycin. Future studies validating the clinical efficacy of this combination strategy are warranted.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Drug Resistance, Multiple, Bacterial , Liver Transplantation/adverse effects , Pseudomonas Infections/drug therapy , Pseudomonas aeruginosa/drug effects , Anti-Bacterial Agents/pharmacology , Bacteremia/microbiology , Bile Duct Diseases/drug therapy , Bile Duct Diseases/microbiology , Carbapenems/therapeutic use , Colistin/analogs & derivatives , Colistin/therapeutic use , Doripenem , Drug Therapy, Combination , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Pseudomonas Infections/microbiology , Tobramycin/therapeutic use , Treatment Outcome
14.
Transpl Infect Dis ; 12(6): 561-4, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21040283

ABSTRACT

Organisms contained in probiotics are generally regarded as non-pathogenic and safe to administer. However, increasing reports of probiotic-associated infection raise concern over the safety of these products. We report a case of Lactobacillus empyema in a human immunodeficiency virus-infected lung transplant recipient receiving a probiotic containing Lactobacillus rhamnosus GG. We compare the epidemiology of Lactobacillus infections in heart and lung transplant recipients at our institution before and after the introduction of this probiotic, and discuss the potential mechanism for Lactobacillus within the probiotic to cause infections and disseminate.


Subject(s)
Empyema, Pleural/microbiology , Gram-Positive Bacterial Infections/microbiology , Heart Transplantation/adverse effects , Lacticaseibacillus rhamnosus/pathogenicity , Lung Transplantation/adverse effects , Probiotics/therapeutic use , Empyema, Pleural/epidemiology , Gram-Positive Bacterial Infections/epidemiology , Humans , Lacticaseibacillus rhamnosus/classification , Lacticaseibacillus rhamnosus/genetics , Lacticaseibacillus rhamnosus/isolation & purification , Male , Middle Aged , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA
15.
Article in English | MEDLINE | ID: mdl-18799855

ABSTRACT

The purpose of this report is to examine longitudinal bone mineral density (BMD) changes in individuals with spinal cord injury (SCI) who began unilateral soleus electrical stimulation early after injury. Twelve men with SCI and seven without SCI underwent peripheral quantitative computed tomography assessment of distal tibia BMD. After 4.5 to 6 years of training, average trained limb BMD was 27.5% higher than untrained limb BMD. The training effect was more pronounced in the central core of the tibia cross-section (40.5% between-limb difference). No between-limb difference emerged in the anterior half of the tibia (19.2 mg/cm(3) difference, p>0.05). A robust between-limb difference emerged in the posterior half of the tibia (76.1 mg/cm(3) difference, p=0.0439). The posterior tibia BMD of one subject remained within the range of non-SCI values for 3.8 years post-SCI. The results support that the constrained orientation of soleus mechanical loads, administered over several years, elicited bone-sparing effects in the posterior tibia. This study provides a demonstration of the bone-protective potential of a carefully controlled dose of mechanical load. The specific orientation of applied mechanical loads may strongly influence the manifestation of BMD adaptations in humans with SCI.


Subject(s)
Adaptation, Physiological , Electric Stimulation Therapy , Muscle, Skeletal/physiopathology , Spinal Cord Injuries/physiopathology , Tibia/diagnostic imaging , Tibia/physiopathology , Weight-Bearing , Acute Disease , Adult , Bone Density , Chronic Disease , Cohort Studies , Humans , Longitudinal Studies , Male , Middle Aged , Reproducibility of Results , Spinal Cord Injuries/therapy , Tibia/metabolism , Tomography, X-Ray Computed/methods , Young Adult
16.
J Biomech ; 40(12): 2587-95, 2007.
Article in English | MEDLINE | ID: mdl-17316653

ABSTRACT

Spinal cord injury (SCI) results in major musculoskeletal adaptations, including muscle atrophy, faster contractile properties, increased fatigability, and bone loss. The use of functional electrical stimulation (FES) provides a method to prevent paralyzed muscle adaptations in order to sustain force-generating capacity. Mathematical muscle models may be able to predict optimal activation strategies during FES, however muscle properties further adapt with long-term training. The purpose of this study was to compare the accuracy of three muscle models, one linear and two nonlinear, for predicting paralyzed soleus muscle force after exposure to long-term FES training. Further, we contrasted the findings between the trained and untrained limbs. The three models' parameters were best fit to a single force train in the trained soleus muscle (N=4). Nine additional force trains (test trains) were predicted for each subject using the developed models. Model errors between predicted and experimental force trains were determined, including specific muscle force properties. The mean overall error was greatest for the linear model (15.8%) and least for the nonlinear Hill Huxley type model (7.8%). No significant error differences were observed between the trained versus untrained limbs, although model parameter values were significantly altered with training. This study confirmed that nonlinear models most accurately predict both trained and untrained paralyzed muscle force properties. Moreover, the optimized model parameter values were responsive to the relative physiological state of the paralyzed muscle (trained versus untrained). These findings are relevant for the design and control of neuro-prosthetic devices for those with SCI.


Subject(s)
Exercise , Models, Biological , Muscle, Skeletal/physiopathology , Muscular Atrophy/physiopathology , Paresis/physiopathology , Adult , Humans , Male , Spinal Cord Injuries/physiopathology , Time Factors
17.
J Appl Physiol (1985) ; 82(5): 1499-507, 1997 May.
Article in English | MEDLINE | ID: mdl-9134899

ABSTRACT

We analyzed the twitch and summated torque (tetanus) during repetitive activation and recovery of the human soleus muscle in individuals with spinal cord injury. Thirteen individuals with complete paralysis (9 chronic, 4 acute) had the tibial nerve activated every 1,500 ms with a 20-Hz train (7 stimuli) for 300 ms and a single pulse at 1,100 ms. The stimulation protocol lasted 3 min and included 120 twitches and 120 tetani. Minimal changes were found for the acute group. The chronic group showed a significant reduction in the torque and a significant slowing of the contractile speeds of both the twitch and tetanus. The decrease in the peak twitch torque was significantly greater than the decrease in the peak tetanus torque early during the fatigue protocol for the chronic group. The twitch time to peak and half relaxation time were prolonged during fatigue, which was associated with improved fusion of the tetanus torque. At the end of the fatigue protocol, the decrease in the peak twitch torque was not significantly different from the decrease in the peak tetanus torque. After 5 min of rest, the contractile speeds recovered causing the tetanus to become unfused, but the tetanus torque became less depressed than the twitch torque. The differential responses for the twitch and the tetanus suggest an interplay between optimal fusion created from contractile speed slowing and excitation contraction coupling compromise. These issues make the optimal design of functional electrical stimulation systems a formidable task.


Subject(s)
Muscle Contraction/physiology , Muscle Fatigue/physiology , Muscle, Skeletal/physiopathology , Paralysis/physiopathology , Acute Disease , Adolescent , Adult , Chronic Disease , Electric Stimulation , Female , Humans , Male , Middle Aged , Muscle Fibers, Fast-Twitch/physiology , Muscle Fibers, Slow-Twitch/physiology , Muscle, Skeletal/cytology , Time Factors , Torque
18.
Spine (Phila Pa 1976) ; 22(16): 1873-9, 1997 Aug 15.
Article in English | MEDLINE | ID: mdl-9280023

ABSTRACT

STUDY DESIGN: This prospective study evaluated the abdominal muscle activity during the Isometric bent knee curl and double straight leg lowering exercise. OBJECTIVES: To compare the magnitude of the electromyographic activity across the curl and double straight leg lowering exercise and determine if the muscle synergies were specific to a given exercise. SUMMARY OF BACKGROUND DATA: Abdominal muscle strengthening exercises are frequently recommended in the prevention and rehabilitation of individuals with low back pain. Previous studies comparing the curl exercise with the double straight leg lowering exercise did not support the notion that the double straight leg lowering exercise is more demanding on the abdominal muscles. No previous study examined these two exercises while maintaining a constant pelvic position. METHODS: Fifteen male subjects had the electromyographic activity of the rectus abdominis, the external oblique, and the internal oblique abdominal muscles evaluated during the curl and double straight leg lowering exercise. The same position of the posterior pelvic tilt was maintained between each exercise using feedback from an electrogoniometer attached to the pelvis. RESULTS: The double straight leg lowering exercise resulted in significantly greater activation of the abdominal muscles compared with the curl. Two abdominal muscle synergies emerged during the double straight leg lowering exercise: synergy I exhibited high rectus abdominis, high external oblique, and low internal oblique muscle activity, whereas synergy II exhibited low rectus abdominis, high external oblique, and high internal oblique. CONCLUSIONS: The results support the use of the double straight leg lowering with the posterior pelvic tilt for achieving greater abdominal muscle coactivation in an exercise program.


Subject(s)
Abdominal Muscles/physiology , Electromyography , Exercise , Leg , Pelvis/physiology , Posture/physiology , Adult , Humans , Male , Muscle Contraction/physiology , Prospective Studies
19.
Phys Ther ; 68(11): 1682-6, 1988 Nov.
Article in English | MEDLINE | ID: mdl-3186795

ABSTRACT

The purpose of this study was to compare the effects of a lumbar support at two seat angles (0 degrees and 10 degrees of posterior tilt) on the area of highest buttock pressure. Twenty able-bodied subjects were seated on a pressure-sensing transducer incorporated into an adjustable chair (ischiobarograph). A video camera on the underside of the transducer detected changes in light levels in direct relation to pressure application. The camera output was processed by a microcomputer system that converted the signal into nine colors, each representing a distinct pressure interval in the range of 0 to more than 500 mm Hg. The microcomputer determined the area of each pressure interval before and after a 10-degree posterior tilt of the seat and lumbar support placement. The results demonstrated high test-retest reliability for each position (r = .95). A significant decrease in the six highest pressure intervals occurred when the lumbar support was used in both the upright and reclined positions (p less than .05). The results of this study have implications for wheelchair-dependent individuals.


Subject(s)
Buttocks , Posture , Pressure Ulcer/prevention & control , Pressure , Wheelchairs , Female , Humans , Male , Manometry/instrumentation , Reference Values
20.
Phys Ther ; 72(3): 218-26, 1992 Mar.
Article in English | MEDLINE | ID: mdl-1584855

ABSTRACT

We compared the effects of different lumbar support thicknesses on seated buttock pressure in individuals with and without spinal cord injury (SCI). Eighteen subjects with SCI (SCI group) and 18 subjects without SCI (control group) were seated on a pressure-sensing transducer incorporated into an adjustable chair. The output was calibrated so that eight pressure intervals (colors) were displayed. The lumbar support thickness was adjusted to 0, 2.5, 5, and 7.5 cm, and the highest and lowest seated buttock pressures were analyzed. External measurements of the hip angle were taken for each lumbar support condition. High reliability of repeated seated test positions was found (intraclass correlation coefficient = .93). The 5- and 7.5-cm-thick lumbar supports caused a decrease in the highest pressure areas in the control group, but no change in the SCI group. The hip angle was increased with each increment in lumbar support thickness in both groups, but the SCI group's hip angle was consistently less than that of the control group for each lumbar support condition. The results of this study suggest that in individuals with chronic paralysis (greater than or equal to 3 years), the use of a wheelchair lumbar support has a negligible effect on seated buttock pressure.


Subject(s)
Buttocks/physiopathology , Interior Design and Furnishings/standards , Orthotic Devices/standards , Pressure Ulcer/physiopathology , Pressure , Spinal Cord Injuries/complications , Adult , Analysis of Variance , Diagnosis, Computer-Assisted , Ergonomics , Evaluation Studies as Topic , Female , Hip Joint/anatomy & histology , Humans , Male , Middle Aged , Monitoring, Physiologic , Posture , Pressure Ulcer/etiology , Pressure Ulcer/prevention & control
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