Pharmacokinetic Analysis of Intravenous Push Cefepime in Burn Patients with Augmented Renal Clearance.

Patients with augmented renal clearance (ARC) are a subset of critically ill patients including burn patients that exhibit increased renal elimination of medications beyond that of similarly injured patients. Currently approved maximum regimens of medications primarily eliminated by the kidney, such as cefepime (>90% unchanged in the urine), may be inadequate (eg, compromising the bactericidal activity of cefepime) in patients with ARC. Due to recent resource limitations, centers have changed infusion practices of commonly prescribed medications to intravenous push (IVP), potentially exacerbating the problem of maintaining bactericidal cefepime concentrations. The hypothesis of the study was patients with ARC are not currently achieving adequate target attainment, when receiving cefepime 2 g every 8 h IVP. Eight blood samples were collected from each patient, and concentrations measured via LC-MS/MS. WinNonlin (version 8.3) was used to estimate the pharmacokinetic parameters of cefepime and simulate plasma concentrations of cefepime in each of the ten subjects. Simulations of cefepime plasma concentrations produced by a 2 g dose given every 8 h and a 1 g dose given every 4 h were performed and the time above a MIC of 4 mg/L, 8 mg/L, and 16 mg/L compared. The 2 g every 8 h regimen remained above the breakpoints for 92%, 85%, and 71% of the dosing interval, respectively. The 1 g every 4 h regimen remained above the same breakpoints at a frequency of 100%, 99%, and 92% of the dosing interval. Giving cefepime 1 g every 4 h is a simple approach to increase the likelihood of maintaining the optimal bactericidal activity of cefepime in patients with ARC.

Tigecycline to treat Stenotrophomonas maltophilia ventilator-associated pneumonia in a trauma intensive care unit as a result of a drug shortage: A case series.

WHAT IS KNOWN AND OBJECTIVE: Stenotrophomonas maltophilia is an intrinsically multidrug-resistant (MDR) organism which commonly presents as a respiratory tract infection. S. maltophilia is typically treated with high-dose sulfamethoxazole/trimethoprim (SMX/TMP). However, SMX/TMP and other treatment options for S. maltophilia can be limited because of resistance, allergy, adverse events or unavailability of the drug; use of novel agents may be necessary to adequately treat this MDR infection and overcome these limitations. CASE DESCRIPTION: This small case series describes two patients who underwent treatment with tigecycline for ventilator-associated pneumonia (VAP) caused by S. maltophilia after admission to a trauma intensive care unit. At the time of admission for the two reported patients, a national drug shortage of intravenous (IV) SMX/TMP prevented its use. Tigecycline was chosen as a novel agent to treat S. maltophilia VAP based on culture and susceptibility data, and it was used successfully. Both patients showed clinical signs of improvement with eventual cure and discharge from the hospital after treatment with tigecycline, and one patient demonstrated confirmed microbiological cure with a negative repeat bronchoscopic bronchoalveolar lavage (BAL). WHAT IS NEW AND CONCLUSION: To our knowledge, this small case series is the first documentation of utilizing tigecycline to treat S. maltophilia VAP in the United States. Although it likely should not be considered as a first-line agent, tigecycline proved to be an effective treatment option in the two cases described in the setting of a national drug shortage of the drug of choice.

Inhaled amikacin adjunctive to intravenous standard-of-care antibiotics in mechanically ventilated patients with Gram-negative pneumonia (INHALE): a double-blind, randomised, placebo-controlled, phase 3, superiority trial.

BACKGROUND: Treatment of ventilated pneumonia is often unsuccessful, even when patients are treated according to established guidelines. Therefore, we aimed to investigate the efficacy of the combination drug device Amikacin Inhale as an adjunctive therapy to intravenous standard-of-care antibiotics for pneumonia caused by Gram-negative pathogens in intubated and mechanically ventilated patients. METHODS: INHALE was a prospective, double-blind, randomised, placebo-controlled, phase 3 study comprising two trials (INHALE 1 and INHALE 2) done in 153 hospital intensive-care units in 25 countries. Eligible patients were aged 18 years or older; had pneumonia that had been diagnosed by chest radiography and that was documented as being caused by or showing two risk factors for a Gram-negative, multidrug-resistant pathogen; were intubated and mechanically ventilated; had impaired oxygenation within 48 h before screening; and had a modified Clinical Pulmonary Infection Score of at least 6. Patients were stratified by region and disease severity (according to their Acute Physiology and Chronic Health Evaluation [APACHE] II score) and randomly assigned (1:1) via an interactive voice-recognition system to receive 400 mg amikacin (Amikacin Inhale) or saline placebo, both of which were aerosolised, administered every 12 h for 10 days via the same synchronised inhalation system, and given alongside standard-of-care intravenous antibiotics. All patients and all staff involved in administering devices and monitoring outcomes were masked to treatment assignment. The primary endpoint, survival at days 28-32, was analysed in all patients who received at least one dose of study drug, were infected with a Gram-negative pathogen, and had an APACHE II score of at least 10 at diagnosis. Safety analyses were done in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, numbers NCT01799993 and NCT00805168. FINDINGS: Between April 13, 2013, and April 7, 2017, 807 patients were assessed for eligibility and 725 were randomly assigned to Amikacin Inhale (362 patients) or aerosolised placebo (363 patients). 712 patients received at least one dose of study drug (354 in the Amikacin Inhale group and 358 in the placebo group), although one patient assigned to Amikacin Inhale received placebo in error and was included in the placebo group for safety analyses. 508 patients (255 in the Amikacin Inhale group and 253 in the placebo group) were assessed for the primary endpoint. We found no between-group difference in survival: 191 (75%) patients in the Amikacin Inhale group versus 196 (77%) patients in the placebo group survived until days 28-32 (odds ratio 0·841, 95% CI 0·554-1·277; p=0·43). Similar proportions of patients in the two treatment groups had a treatment-emergent adverse event (295 [84%] of 353 patients in the Amikacin Inhale group vs 303 [84%] of 359 patients in the placebo group) or a serious treatment-emergent adverse event (101 [29%] patients vs 97 [27%] patients). INTERPRETATION: Our findings do not support use of inhaled amikacin adjunctive to standard-of-care intravenous therapy in mechanically ventilated patients with Gram-negative pneumonia. FUNDING: Bayer AG.

Keeping it Simple: Impact of a Restrictive Antibiotic Policy for Ventilator-Associated Pneumonia in Trauma Patients on Incidence and Sensitivities of Causative Pathogens.

BACKGROUND: An integral part of ventilator-associated pneumonia (VAP) therapy is the appropriate choice of empiric antibiotics. Our previous experience demonstrated adherence to an empiric therapy pathway was associated with only modest changes in organisms causing VAP. The purpose of the current study was to evaluate the impact of a restrictive antibiotic policy for VAP in trauma patients on the incidence and sensitivities of causative pathogens since the previous study. PATIENTS AND METHODS: Patients with VAP diagnosed on bronchoalveolar lavage since the previous study were stratified by age, gender, mechanism of injury, and injury severity. All patients received empiric antibiotics based on duration of intensive care unit (ICU) stay using a unit-specific pathway. The incidence and sensitivities of causative pathogens in the current study were documented. The adequacy of the VAP pathway was evaluated for all VAP episodes. The current study was then compared with the previous study. RESULTS: Over a 10-year period, 1,474 episodes of VAP were diagnosed with 2,387 causative pathogens isolated. Overall incidence of gram-positive and gram-negative VAP pathogens was unchanged between the study periods. The current study experienced an increase in the incidence of Staphylococcus aureus (23% vs. 17%, p = 0.001) and methicillin-resistant Staphylococcus aureus (10% vs. 6%, p = 0.002) compared with the previous study. The pathway for empiric antibiotics resulted in adequate empiric coverage in 85% of VAP episodes, which was improved compared with the previous study (76%, p = 0.024). Furthermore, despite the increased incidence of early methicillin-resistant Staphylococcus aureus (MRSA) VAP, adequacy of the pathway improved for both the early period (91% vs. 86%, p = 0.001) as well as the late period (86% vs. 63%, p < 0.001) in the current study compared with the previous study. CONCLUSIONS: A comprehensive protocol for the diagnosis and management of VAP, along with antibiotic stewardship, can prevent the development of bacterial resistance to empiric therapy.

Use of Aerosolized Antibiotics in Gram-Negative Ventilator-Associated Pneumonia in Trauma Patients.

Ventilator-associated pneumonia (VAP) is associated with significant morbidity (ventilator days, ICU days, and cost) and mortality increase in trauma patients. Multidrug-resistant strains of causative VAP pathogens are becoming increasingly common. Aerosolized antibiotics achieve high alveolar concentrations and provide valuable adjuncts in the treatment of VAP. This study examined the impact of aerosolized antibiotics in the treatment of VAP in trauma patients. Patients with either Acinetobacter baumannii or Pseudomonas aeruginosa VAP over 10 years treated with aerosolized antibiotics (cases) were stratified by age, severity of shock, and injury severity. A frequency-matched (by causative pathogen) control group treated without aerosolized antibiotics was used for comparison. Multivariable logistic regression was used to identify predictors for the use of aerosolized antibiotics. One hundred twenty VAP episodes were identified in 100 patients. Microbiologic resolution was achieved in all patients treated with aerosolized antibiotics. There was no difference in mortality (14.5% vs 15.7%, P = 0.87) and no antibiotic-related complications in either group. Multivariable logistic regression identified VAP persistence and relapse as independent predictors for the use of aerosolized antibiotics. Combined with systemic therapy, aerosolized antibiotics broaden the spectrum of therapy. They are valuable adjuncts with minimal risk of antibiotic resistance and/or systemic complications.

Treatment of Achromobacter Ventilator-Associated Pneumonia in Critically Ill Trauma Patients.

BACKGROUND: Achromobacter sp are nonfermenting Gram-negative bacilli (NFGNB) that rarely cause severe infections, including ventilator-associated pneumonia (VAP). Data on the treatment of Achromobacter pneumonia are very limited, and the organism has been associated with a high mortality rate. Thus, more data are needed on treating this organism. OBJECTIVE: To evaluate the treatment of Achromobacter VAP in critically ill trauma patients. METHODS: This retrospective, observational study evaluated critically ill trauma patients who developed Achromobacter VAP. A previously published pathway for the diagnosis and management of VAP was used according to routine patient care. This included the use of quantitative bronchoscopic bronchoalveolar lavage cultures to definitively diagnose VAP. RESULTS: A total of 37 episodes of Achromobacter VAP occurred in 34 trauma intensive care unit patients over a 15-year period. The most commonly used definitive antibiotics were imipenem/cilastatin, cefepime, or trimethoprim/sulfamethoxazole. The primary outcome of clinical success was achieved in 32 of 37 episodes (87%). This is similar to previous studies of other NFGNB VAP (eg, Pseudomonas, Acinetobacter) from the study center. Microbiological success was seen in 21 of 28 episodes (75%), and VAP-related mortality was 9% (3 of 34 patients). CONCLUSIONS: Achromobacter is a rare but potentially serious cause of VAP in critically ill patients. In this study, there was an acceptable success rate compared with other causes of NFGNB VAP in this patient population.

Redesigning Journal Clubs to Staying Current with the Literature.

Staying current with the literature is of paramount importance to the pharmacist engaged in an evidence-based clinical practice. Given the expanding roles and responsibilities of today's pharmacists combined with exponential growth in new medical and health sciences literature, staying current has become an extremely daunting task. Traditional journal clubs have focused upon their role as a training vehicle for teaching critical reading skills to residents. However, schools of pharmacy are now required to provide instruction in biostatistics, research design, and interpretation. We present a paradigm shift in the traditional journal club model whereby a collection of periodicals is screened and a short synopsis of the pertinent articles is provided. The associated tasks for screening and presenting of the primary literature are shared among a group of clinicians and trainees with similar practice interests resulting in a more reasonable workload for the individual. This journal club method was effective in identifying a significant majority of articles judged to be pertinent by independent groups of clinicians in the same practice arenas. Details regarding the shared core practice and knowledge base elements, journal club format, identification of journals, and evaluation of the success of the journal club technique are provided.

An Update on Aerosolized Antibiotics for Treating Hospital-Acquired and Ventilator-Associated Pneumonia in Adults.

OBJECTIVE: A significant percentage of patients with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) have poor outcomes with intravenous antibiotics. It is not clear if adding aerosolized antibiotics improves treatment. This review is an update on using aerosolized antibiotics for treating HAP/VAP in adults. DATA SOURCES: PubMed search using the terms "aerosolized antibiotics pneumonia," "nebulized antibiotics pneumonia," and "inhaled antibiotics pneumonia." Reference lists from identified articles were also searched. STUDY SELECTION AND DATA EXTRACTION: Clinical studies of aerosolized antibiotics for treating HAP/VAP in adults from July 2010 to March 2017. This article updates a previous review on this topic written in mid-2010. DATA SYNTHESIS: The size and quality of studies have improved dramatically in the recent time period compared to previous studies. However, there still are not large randomized controlled trials available. Colistin and aminoglycosides were the most commonly studied agents, and the most common pathogens were Pseudomonas and Acinetobacter. The clinical efficacy of adding aerosolized antibiotics was mixed. Approximately half of the studies showed better outcomes, and none showed worse outcomes. Aerosolized antibiotics appear to be relatively safe, though pulmonary adverse events can occur. Attention to proper administration technique in mechanically ventilated patients is required, including the use of vibrating plate nebulizers. CONCLUSIONS: Adding aerosolized antibiotics to intravenous antibiotics may improve the outcomes of adult patients with HAP/VAP in some settings. It seems reasonable to add aerosolized antibiotics in patients with multidrug-resistant organisms or who appear to be failing therapy. Clinicians should pay attention to potential adverse events and proper administration technique.

Pharmacokinetics of Imipenem/Cilastatin Burn Intensive Care Unit Patients Undergoing High-Dose Continuous Venovenous Hemofiltration.

STUDY OBJECTIVE: High-dose continuous venovenous hemofiltration (CVVH) is a continuous renal replacement therapy (CRRT) used frequently in patients with burns. However, antibiotic dosing is based on inference from studies assessing substantially different methods of CRRT. To address this knowledge gap for imipenem/cilastatin (I/C), we evaluated the systemic and extracorporeal clearances (CLs) of I/C in patients with burns undergoing high-dose CVVH. DESIGN: Prospective clinical pharmacokinetic study. PATIENTS: Ten adult patients with burns receiving I/C for a documented infection and requiring high-dose CVVH were studied. METHODS: Blood and effluent samples for analysis of I/C concentrations were collected for up to 6 hours after the I/C infusion for calculation of I/C total CL (CLTotal ), CL by CVVH (CLHF ), half-life during CVVH, volume of distribution at steady state (Vdss ), and the percentage of drug eliminated by CVVH. RESULTS: In this patient sample, the mean age was 50 ± 17 years, total body surface area burns was 23 ± 27%, and 80% were male. Nine patients were treated with high-dose CVVH for acute kidney injury and one patient for sepsis. The mean delivered CVVH dose was 52 ± 14 ml/kg/hour (range 32-74 ml/kg/hr). The imipenem CLHF was 3.27 ± 0.48 L/hour, which accounted for 23 ± 4% of the CLTotal (14.74 ± 4.75 L/hr). Cilastatin CLHF was 1.98 ± 0.56 L/hour, which accounted for 45 ± 19% of the CLTotal (5.16 + 2.44 L/hr). The imipenem and cilastatin half-lives were 1.77 ± 0.38 hours and 4.21 ± 2.31 hours, respectively. Imipenem and cilastatin Vdss were 35.1 ± 10.3 and 32.8 ± 13.8 L, respectively. CONCLUSION: Efficient removal of I/C by high-dose CVVH, a high overall clearance, and a high volume of distribution in burn intensive care unit patients undergoing this CRRT method warrant aggressive dosing to treat serious infections effectively depending on the infection site and/or pathogen.

Short-duration treatment for catheter-associated urinary tract infections in critically ill trauma patients.

BACKGROUND: The optimal treatment duration for catheter-associated urinary tract infection (CA-UTI) in critically ill patients is unclear. The Infectious Diseases Society of America recommends up to 14 days of therapy; however, short-duration therapy (SDT) for 3 days to 5 days is often used in trauma intensive care unit (ICU) patients at our center. The efficacy of SDT for CA-UTI has not been studied in this population. The objective was to evaluate the efficacy of SDT for CA-UTI in trauma ICU patients. METHODS: This retrospective study of patients with CA-UTI in a trauma ICU included patients with a urine culture growing bacteria of 100,000 CFU/mL or greater and definitive antibiotic treatment. Urine cultures were collected as part of standard workups for suspected sepsis. Duration of therapy was at the discretion of the trauma team. Exclusion criteria included concomitant infection, renal replacement therapy, or pregnancy. Clinical success and microbiologic success were evaluated. RESULTS: One hundred ninety-two patients were evaluated, and 77 patients with SDT were included. Mean (SD) age was 49 (22) years, median Injury Severity Score (ISS) was 27 (interquartile range, 18-34), and median ICU stay was 17 days (interquartile range, 1-33 days). Mean (SD) duration of CA-UTI therapy was 4 (1) days (range, 3-5 days) with most patients (42%) receiving 5 days. The most common organisms were Escherichia coli, Enterococcus species, and Pseudomonas species. The clinical success rate was 82% (63 of 77), and the microbiologic success rate was 75% (36 of 48). Overall mortality was 4%, but no deaths were CA-UTI related. CONCLUSION: SDT provided an acceptable clinical success rate in critically ill trauma patients, which was similar to studies of CA-UTI in other populations. These results suggest that SDT could be considered an option for treating CA-UTIs in trauma ICU patients. LEVEL OF EVIDENCE: Therapeutic study, level V.

Adjunctive intraventricular antibiotic therapy for bacterial central nervous system infections in critically ill patients with traumatic brain injury.

BACKGROUND: Limited data exist on the role of adjunctive intraventricular (IVT) antibiotics for the treatment of central nervous system (CNS) infections in traumatic brain injury (TBI) patients. OBJECTIVE: To evaluate differences in CNS infection cure rates for TBI patients who received adjunctive IVT antibiotics compared with intravenous (IV) antibiotics alone. METHODS: We retrospectively identified patients with TBI and bacterial CNS infections admitted to the trauma intensive care unit (ICU) from 1997 to 2013. Study patients received IV and IVT antibiotics, and control patients received IV antibiotics alone. Clinical and microbiological cure rates were determined from patient records, in addition to ICU and hospital lengths of stay (LOSs), ventilator days, and hospital mortality. RESULTS: A total of 83 patients were enrolled (32 study and 51 control). The duration of IV antibiotics was similar in both groups (10 vs 12 days, P = 0.14), and the study group received IVT antibiotics for a median of 9 days. Microbiological cure rates were 84% and 82% in study and control groups, respectively (P = 0.95). Clinical cure rates were similar at all time points. No significant differences were seen in days of mechanical ventilation, ICU or hospital LOS, or hospital mortality. When only patients with external ventricular drains were compared, cure rates remained similar between groups. CONCLUSIONS: TBI patients with CNS infections had similar microbiological and clinical cure rates whether they were treated with adjunctive IVT antibiotics or IV antibiotics alone. Shorter than recommended durations of antibiotic therapy still resulted in acceptable cure rates and similar clinically relevant outcomes.

Adherence to an established diagnostic threshold for ventilator-associated pneumonia contributes to low false-negative rates in trauma patients.

BACKGROUND: The diagnosis of ventilator-associated pneumonia (VAP) in our institution has followed an established diagnostic threshold (DT) of equal to or greater than 10 colony-forming units (CFU) per milliliter on bronchoalveolar lavage (BAL) based on our previous study (PS). Because mortality from VAP is related to treatment delay, some have advocated a lower DT. The purpose of the current study (CS) was to evaluate the impact of adherence to this DT for VAP on false-negative (FN) rates and mortality in trauma patients. METHODS: Consecutive patients over 9 years with VAP (defined as ≥10 CFU/mL in the BAL effluent) subsequent to the PS were identified. Data regarding each BAL performed and the colony counts of each organism identified were recorded. An FN BAL result was defined as any patient who had less than 10 CFU/mL and developed VAP with the same organism up to 7 days after the previous culture. The CS was then compared with the PS. RESULTS: Over 9 years, 1,679 patients underwent 3,202 BALs. Of these, 79% were male, 88% experienced blunt injury, mean age and Injury Severity Score (ISS) were 44 years and 31, respectively. Overall, there were 73 FN BAL results (2.3%) in the CS compared with 3% in the PS (p = 0.092). In those patients with 10 organisms, the FN rate was reduced (7.5% vs. 11%, p = 0.045), and mortality was unchanged (5.4% vs. 8.3%, p = 0.361) in the CS compared with the PS. The use of the threshold equal to or greater than 10 resulted in a cumulative reduction in antibiotic charges of $1.57 million. CONCLUSION: Continued adherence to the diagnostic threshold of equal to or greater than 10 for quantitative BAL in trauma patients has maintained a low incidence of FN BALs and reduced patient charges without impacting mortality. The purported benefit of a lower threshold is not supported. In addition, the potential sequelae of increased resistant organisms, antibiotic-related complications, and costs associated with prolonged unnecessary antibiotic exposure are minimized. LEVEL OF EVIDENCE: Prognostic study, level III.

Impact of pathogen-directed antimicrobial therapy for ventilator-associated pneumonia in trauma patients on charges and recurrence.

BACKGROUND: Ventilator-associated pneumonia (VAP) represents one of the driving forces behind antibiotic use in the ICU. In a previous study, we established a defined algorithm for treatment of hospital-acquired VAP dictated by the causative pathogen. The purpose of the current study was to evaluate the impact of this algorithm for hospital-acquired VAP on recurrence and charges in trauma patients. STUDY DESIGN: Patients with VAP secondary to MRSA, Acinetobacter baumannii, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, or Enterobacteriaceae during 5 years subsequent to the previous study were evaluated. All VAP were diagnosed using quantitative cultures of the bronchoalveolar lavage effluent. Duration of antimicrobial therapy was dictated by the causative pathogen. If microbiologic resolution, defined as <10(3) colony-forming units/mL, was achieved, therapy was stopped by day 10. The remainder received 14 days of therapy. Recurrence was defined as >10(5) colony-forming units/mL on subsequent bronchoalveolar lavage performed within 2 weeks after completion of appropriate therapy. RESULTS: Five hundred and twenty-nine VAP episodes were identified in 381 patients. Overall recurrence was unchanged compared with the previous study (1.5% vs 2%; p = 0.3). There was a decrease in the number of bronchoalveolar lavages performed per patient compared with the previous study (1.6 vs 2.3; p = 0.24) and a reduction of 4.8 antibiotic days per VAP episode compared with the previous study. Both changes resulted in a cumulative reduction of $3,535.04 per patient, for a savings of $1.35 million during the study period. CONCLUSIONS: Hospital-acquired VAP can be managed effectively by a defined course of therapy dictated by the causative pathogen. Adherence to an established algorithm simplified the management of VAP and contributed to a cumulative reduction in patient charges without impacting recurrence.

Linezolid bladder irrigation as adjunctive treatment for a vancomycin-resistant Enterococcus faecium catheter-associated urinary tract infection.

OBJECTIVE: To describe the first reported successful use of adjunctive linezolid bladder irrigation. CASE SUMMARY: An 89-year-old woman with 10% TBSA burns developed septic shock and anuric acute kidney insufficiency. She acquired a urinary tract infection caused by vancomycin-resistant Enterococcus faecium (VREfm). Based on clinical status, a linezolid bladder irrigation was initiated in addition to high-dose intravenous linezolid and demonstrated microbiological cure with 7 days of treatment. DISCUSSION: Linezolid is primarily hepatically cleared and has no labeled indication for urinary tract infections. Anuria adds an additional complication of potentially reduced urinary drug concentrations. Bladder irrigation offers the benefit of achieving high local drug concentrations, but there are no data regarding such a route for linezolid. This case report is the first demonstrating the use, stability, safety, and efficacy of linezolid as a continuous bladder irrigation. CONCLUSIONS: Linezolid use as a bladder irrigation may be a feasible route of administration in anuric, critically ill patients with VREfm and few antimicrobial options. Further studies are warranted.

Effectiveness of pseudoephedrine as adjunctive therapy for neurogenic shock after acute spinal cord injury: a case series.

STUDY OBJECTIVE: To evaluate the effectiveness of pseudoephedrine as adjunctive therapy for neurogenic shock in patients with acute spinal cord injury (SCI). DESIGN: Case series. SETTING: Academic medical center. PATIENTS: Thirty-eight patients admitted to the trauma intensive care unit between September 2005 and October 2012 with an acute SCI and who received more than 1 day of pseudoephedrine for one or more of the following: treatment of bradycardia (heart rate ≤ 50 beats/min), treatment of hypotension (systolic blood pressure < 90 mm Hg), or were receiving intravenous vasopressor support. MEASUREMENTS AND MAIN RESULTS: The effect of adjunctive pseudoephedrine (PSE) was categorized as a success if vasopressors were discontinued after the initiation of PSE or improvement in the number of episodes of bradycardia was noted after the initiation of PSE as evidenced by decreased use of atropine. The effect of pseudoephedrine was categorized as a failure if it did not meet one of the criteria for success. The effect of pseudoephedrine was categorized as inconclusive if there were confounding factors such as vasopressors being restarted for another indication after initial discontinuation. Pseudoephedrine was successful in 31/38 (82%) patients, failed in 2/38 (5%) patients, and had inconclusive results in 5/38 (13%) patients. The mean ± SD time to successful weaning of intravenous vasopressors was 7 ± 7 days. Daily maximum pseudoephedrine doses ranged from 60-720 mg. Mean ± SD duration of pseudoephedrine therapy was 32 ± 23 days (range 2-135 days), with 64.5% of surviving patients discharged while receiving pseudoephedrine. CONCLUSION: These data suggest that pseudoephedrine is an effective adjunctive therapy in facilitating the discontinuation of intravenous vasopressors and/or atropine in patients with acute SCI with neurogenic shock, although patients will typically require long durations of therapy.

Sustainability of Improved Glycemic Control After Diabetes Self-Management Education.

Objective. The purpose of this study was to evaluate glycemic control as measured by A1C during a 2-year period after patients received diabetes self-management education (DSME). Methods. Patients who completed DSME in 2009 and received medical follow-up with A1C measurements for at least 2 years after DSME were included in the evaluation. Primary endpoints were changes in A1C from before to immediately after, 1 year after, and 2 years after DSME. Secondary outcomes included the effects of the following factors on change in A1C: sex, duration of diabetes, uncontrolled diabetes (A1C ≥ 9%), health insurance coverage, and self-reported education level. Results. Forty-three patients were included in the evaluation. Mean A1C before DSME was 10.2 ± 3.7%. Mean A1C after DSME was 7.8 ± 2.2% (P < 0.0001), a 23.5% reduction. Mean A1C at 1 and 2 years after DSME was 7.8 ± 2.1% for each year and remained unchanged from just after DSME to 1 and 2 years after DSME (P > 0.05). Patients with a duration of diabetes of < 1 year had a significantly greater reduction in mean A1C than those with a duration of diabetes ≥ 1 year (28.7 and 20.2%, respectively, P = 0.001). Conclusion. DSME improved glycemic control to a substantial degree, and the effect was sustained for up to 2 years. Although the reduction in A1C was significant for all patients receiving DSME, there was a significantly greater reduction for patients who had a duration of diabetes of < 1 year than for those with a duration of diabetes > 1 year.

Treatment of Rhizobium radiobacter bacteremia in a critically ill trauma patient.

OBJECTIVE: To report the first case of Rhizobium radiobacter bacteremia in a critically ill trauma patient. CASE SUMMARY: A 36-year-old female trauma patient hospitalized at The Regional Medical Center at Memphis developed bacteremia due to Rhizobium radiobacter on hospital day 9. The central line catheter tip culture from the same hospital day was negative. No source for the R radiobacter bacteremia was identified. Empirical and definitive antibiotic therapy consisted of cefepime 2 g intravenously every 8 hours for at total of 8 days. On completion of antibiotics, the patient demonstrated clinical resolution by immediate defervescence and gradual normalization of her white blood cell count. She demonstrated microbiologic success of therapy with negative blood cultures on hospital days 22, 34, 45, and 61. She was discharged on hospital day 80. DISCUSSION: Rhizobium species are common soil and plant pathogens that rarely cause infections in humans. Previous reports of Rhizobium infections have been in immunocompromised patients; generally those with cancer or HIV infection. Intravenous catheters have commonly been cited as the source of infection. The trauma patient in this case constitutes a unique presentation of R radiobacter bacteremia when compared with other case reports. Her indwelling catheter was not the source of her infection, and her only identifiable risk factor for R radiobacter infection was hospitalization. However, she did possess potential reasons for development of an infection with an unusual organism such as R radiobacter. Potential immune modulating therapies included blood transfusions, opioid analgesics, benzodiazepines, general anesthetics, and surgical procedures. Finally, trauma itself has been associated with some degree of immunosuppression. All these issues may have placed the patient in this case at risk of an opportunistic infection like R radiobacter. CONCLUSION: Based on this case, R radiobacter may be considered a potential pathogen causing bacteremia in critically ill trauma patients.

Treatment of Chryseobacterium indologenes ventilator-associated pneumonia in a critically ill trauma patient.

OBJECTIVE: To report a case of Chryseobacterium indologenes ventilator-associated pneumonia (VAP) in a critically ill trauma patient. CASE SUMMARY: This report describes a 66-year-old critically ill trauma patient who developed VAP, which was caused by C indologenes. The patient was injured in a riding lawn mower accident that trapped him underwater in a pond. The patient required surgery for intra-abdominal injuries and was mechanically ventilated in the trauma intensive care unit. On hospital day 5, the patient developed signs and symptoms of VAP. A diagnosis of C indologenes VAP was confirmed based on a quantitative culture from a bronchoscopic bronchoalveolar lavage. The patient's infection was successfully treated with moxifloxacin for 2 days followed by cefepime for 7 days. DISCUSSION: Formally known as Flavobacterium indologenes, C indologenes is a Gram-negative bacillus normally found in plants, soil, foodstuffs, and fresh and marine water sources. Recently, worldwide reports of C indologenes infections in humans have been increasing, though reports from the United States are still rare. Bacteremia and pneumonia are the most commonly reported infections, and most patients are immunocompromised. The current case differs from most previous reports because this patient was in the United States and did not have any traditional immunocompromised states (eg, transplant, cancer, HIV/AIDS, or corticosteroid use). CONCLUSION: This case report demonstrates that C indologenes can cause VAP in a trauma ICU patient.

Resolution of clinical and laboratory abnormalities after diagnosis of ventilator-associated pneumonia in trauma patients.

BACKGROUND: Guidelines advise that patients with ventilator-associated pneumonia (VAP) should respond clinically by Day 3 of antibiotics. White blood cell (WBC) count, maximum temperature (Tmax), and PaO2:FIO2 ratio are all said to respond significantly by Day 6. Resolution of abnormalities has not been evaluated in trauma patients. METHODS: Retrospective review of trauma patients with VAP. The WBC count, Tmax, and PaO2:FIO2 were evaluated for 16 days after diagnosis. Patients were grouped into uncomplicated VAP, complicated VAP (those with inadequate empirical therapy [IEAT], VAP relapse/superinfection, or acute respiratory distress syndrome), and concurrent infection+VAP (those also infected at another site). RESULTS: There were 126 patients (uncomplicated VAP=29, complicated VAP=69, and concurrent infection+VAP=28). The mean Tmax in patients with uncomplicated VAP decreased significantly from diagnosis to Day 4 (Day 1: 39 ± 0.5°C vs. Day 4: 38.6 ± 0.7°C; p=0.028) but never normalized. Their WBC counts and PaO2:FIO2 did not change significantly over the 16-day follow-up and never normalized. When comparing the three groups, the probability of resolving all three abnormalities was not different (p=0.5). CONCLUSIONS: Clinical and laboratory abnormalities in critically injured patients with VAP do not resolve as quickly as suggested in the guidelines. Future studies should evaluate new methods to determine the response to antibiotic therapy in critically injured patients with VAP.