Antimicrobial Selection in the Face of Nasal Methicillin-Resistant Staphylococcus aureus-Polymerase Chain Recombination Testing in Thermal Injury Patients.

Emergence of resistance to vancomycin and the increasing incidence of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) warrant careful initiation of antimicrobial agents after nasal swab polymerase chain recombination (PCR) MRSA positive screen. Current MRSA PCR nasal swab (PCR) screening does not distinguish non-hospital-acquired strains. A retrospective, institutional review board-approved study of collected PCR screenings among 826 burn center admissions over a 23-month period assessed culture results, antimicrobial agents chosen, and patient demographics. Seventy-seven of the 826 were known chronic carriers (n = 11); had MRSA on initial PCR (n = 48); or converted to positive PCR screen on later testing (n = 18). The 48 patients with initial positive PCR were decolonized with mupirocin. MRSA carriers were not decolonized. The 18 patients who became PCR positive were also not decolonized with 10 having positive cultures. The 48 initial PCR nasal swab positive patients represented 5.8% of admissions. Demographic data did not differ among chronic carriers, initial PCR positive patients, nor those converting to PCR positive. Length of stay was shorter for initial PCR positive decolonized patients (P << .05) and they had a 35% of decrease in MRSA infection. All 11 chronic carriers became infected with MRSA; however, five had non-hospital-acquired MRSA and two solely non-hospital-acquired MRSA. For the 48 PCR positive patients, 17 had isolated MRSA and one having exclusively non-hospital-acquired MRSA. Of the 39 patients with isolated MRSA, 20 (43%) non-hospital-acquired MRSA. Non-hospital-acquired MRSA was 43%, however PCR fails to distinguish hospital-acquired MRSA from community-acquired MRSA.

Pyoderma gangrenosum: a difficult diagnosis best managed in a burn treatment center.

Pyoderma gangrenosum (PG) is a rare immunological disorder with inexplicable white blood cell infiltration into the epidermis with necrosis and excruciating pain. Diagnosis is by exclusion which delays proper treatment. Surgical intervention often exacerbates wounds. Between 2004 and 2010, seven patients with PG were admitted to our burn treatment center (BTC). Multiple treatment modalities were used on these patients. An institutional review board-approved retrospective study investigated seven PG BTC admissions. Demographic information, symptom onset, time to diagnosis, admission or transfer, length of stay (LOS), use of corticosteroids, and prior surgery were collected. The average time to PG diagnosis was 18.7 days and the average wound surface area was 3.9%. The average patient age was 64.6 years (median 66 years) and there were five men and two women patients. The average symptom onset was 70.5 days prior to BTC admission. The BTC wound care lasted 24 days. Six of the seven patients had lower extremity lesions vs one with lesions involving the abdomen. Inflammatory bowel disease was noted in two patients, one with malignant melanoma, and another with psoriasis. Corticosteroids were begun 1.75 days after admission for six of the seven patients. Of the seven PG patients, five had excision and/or skin grafting with vacuum-assisted wound closure used in four. Six patients were discharged, but one patient succumbed early to sepsis. Skin grafting often speeds up chronic wound closure; however for PG this causes progression of lesions. Persistent non-healing wounds with pain disproportionate to size may be PG. Prompt diagnosis and BTC specialized care greatly improve outcomes for PG patients.

Trimethoprim-induced hyperkalemia in burn patients treated with intravenous or oral trimethoprim sulfamethoxazole for methicillin-resistant Staphylococcus aureus and other infections: nature or nurture?

Trimethoprim is well known to cause rashes; however, what is not commonly known is that it causes sudden and profound hyperkalemia in 10 to 20% of treated patients. The uniqueness of burn patients begs the question whether changes known to occur in these patients might also increase this trimethoprim effect. After institutional review board approval, a retrospective study evaluated 224 patients with thermal injury who had been treated with trimethoprim sulfamethoxazole (TMP-SMX), 24 of whom had underlying renal impairment (creatinine clearances <50 ml/min) and were excluded, leaving 200 patients for analysis. Three definitions of drug-induced hyperkalemia were used: 1) a ≥ 1 mEq/L rise, 2) a >0.8 mEq rise in potassium in <24 hours warranting early discontinuation of TMP-SMX, and 3) "marked" hyperkalemia defined as serum potassium of ≥ 5.5 mEq/L within 48 hours. A potassium level before trimethoprim exposure (TxK) and after TxK were collected retrospectively. Demographic data were analyzed with Student's t-test and trimethoprim dose alone, demonstrating a significant difference. Analysis of 200 patients exposed to trimethoprim demonstrated an elevation of potassium (first definition) in 31 patients (15.5%), a rapid change in serum potassium in two patients (second definition), and marked hyperkalemia (>5.5 mEq/L) in 13 patients (6.5%). Hyperkalemia never occurred in 166 of 200 patients (82%; before TxK, 3.9 ± 0.4; after TxK, 4.3 ± 0.5 mEq/L). Change in serum potassium among patients with hyperkalemia was 4.0 ± 0.5 mEq/L before TxK and 5.3 ± 0.7 mEq/L after TxK. Twelve published hyperkalemia risk factors were reviewed in these 200 patients and only history of hypertension and need for intubation was more common in those with hyperkalemia. A nearly 20% incidence of hyperkalemia and 6% serious hyperkalemia in burn patients is consistent with reports in patients without burn injury. These data also suggest that the metabolic and hormonal changes associated with burn injury do not increase further the genetically predisposed hyperkalemia resulting from exposure to trimethoprim. These data suggest patients treated with TMP-SMX should have routine serum potassium monitoring before discharge.

Evaluation of the relationship between elevated vancomycin trough concentrations and increased efficacy and/or toxicity.

Isolation of Staphylococcus aureus with minimum inhibitory concentrations, 1 to 2 mg/L, suggests increasing vancomycin trough ranges, from 10 to 20 mg/L or even higher. Vancomycin troughs from 604 treatment courses from 560 patients with suspected or actual Gram-positive infection were analyzed with focus on potential toxicity/efficacy. Trough concentrations were required to be drawn within 15 to 45 minutes before the administration of at least the third vancomycin dose. Patients were retrospectively evaluated for their total daily dose and milligrams per kilograms per vancomycin dose. Data on the duration of vancomycin therapy, days to a normal temperature, and white blood cells were obtained. Data were stratified by trough concentration as <5, 5 to 10, and >10 mg/L to determine whether there was any relationship between response and trough concentration. Demographic data were obtained in 560 patients with 604 vancomycin treatment courses. For 361 patients with 379 separate treatment courses of vancomycin therapy no other nephrotoxic antimicrobial agent had been used. The greatest risk of vancomycin nephrotoxicity correlated with the duration of treatment. Using the log time to normal temperature, white blood cell count, heart rate, outcome from vancomycin therapy was assessed and no relationship could be demonstrated for the three vancomycin trough strata using analysis of variance (F < 2.62 for all parameters; p > .05). These data indicate that vancomycin trough elevation may not guarantee treatment success and that there may be no real benefit from higher vancomycin trough concentrations in thermal injury patients with burns <20% TBSA.

A comparison of clinical and microbiological efficacy of antibiotic regimens against Acinetobacter baumannii.

Acinetobacter baumannii represents a cunning pathogen with multiple resistance genes. The authors report their experience with the treatment of two multiple drug-resistant A. baumannii clones. At least one positive culture was noted in 359 patients and, 323 had sufficient data for analysis. Of these, 42 patients were colonized leaving 281 antibiotic-treated infected patients. The average age was 48.1 ± 20.6 years (mean ± standard deviation), total body burn surface area involvement (TBSA) was 30.8 ± 25%. Inhalation injury was confirmed by bronchoscopy in 238 of 323 (74%) patients. The day to the first A. baumannii culture was 7.9 ± 8.9 and 6.5 ± 8.8 days for the colonized and infected patients, respectively. Survival to discharge was 95.4% for colonized patients and 77.1% for infected patients. A total of 1425 sputum cultures, 123 catheter cultures from 40 patients, 1130 blood cultures from 176 patients, and 1925 wound cultures were obtained from the 318 infected patients (14 cultures per patient). Imipenem-cilastatin was first used in 162 patients, ampicillin-sulbactam in 40 patients, and cephalosporin in 41 patients. Imipenem-cilastatin was combined with ampicillin-sulbactam in 18 patients. Imipenem-cilastatin eradicated A. baumannii in 27%, caused persistence in 55%, and failure in 20%. Ampicillin-sulbactam eradicated A. baumannii in 17%, caused persistence in 51%, and failure in 34%. Imipenem-cilastatin combined with ampicillin-sulbactam eradicated 23% of the A. baumannii, with 54% persisting, and 23% failing therapy. Nonparametric analysis of three sets of 34 matched patients treated with imipenem-cilastatin, ampicillin-sulbactam, or a cephalosporin showed little difference in treatment outcomes. More rapid fever resolution and fewer positive cultures were noted in the imipenem-cilastatin treated group; however, length of stay was not different.

Use of nebulized antimicrobial agents in burned and mechanically ventilated patients with persistent Acinetobacter baumannii, Pseudomonas aeruginosa, or Enterobacteriacea.

BACKGROUND: Nebulized antibiotics are used to locally treat colonizations of multi-resistant organisms. Prior systemic nephrotoxic antibiotic use with serum creatinine rises warranted an alternative therapy in 69 ventilator-dependent patients with persisting sputum cultures and need for ventilatory support. MATERIALS AND METHODS: Following IRB approval, retrospective patient data were reviewed. Analysis included comparison of these 69 patients (71 treatments) to 142 Gram-negative infected burn patients matched for age and burn size. RESULTS: Mean pooled age and burn wound percent for the 71 triplicates (n=211 patients) were 55.6±18.3 years and 27.4±22.3% burns. Fifty-seven of 69 (83%) patients had inhalation injuries and 54 of 69 (78%) patients survived. Nebulizations averaged 6.8±3.3 days (range 3-12 days). Serum creatinine rose in 2 patients receiving colistimethate nebulizations, known to cause nephrotoxicity following nebulization. Triplicate comparisons via ANOVA noted prolonged ventilatory support (F=13.39; p≪0.05) and length of stay (F=6.11; p≪0.5). Variance was attributed to the sicker nebulized patients. Twenty-four inhalation injury-only triplicates further confirmed that nebulized patient subgroup was more ill. CONCLUSION: Short duration antibiotic nebulization may allow higher intra-tracheal antibiotic concentrations and may facilitate weaning from the ventilator by reducing bacterial bioburden.

Emergence of resistance of vancomycin-resistant Enterococcus faecium in a thermal injury patient treated with quinupristin-dalfopristin and cultured epithelial autografts for wound closure.

Vancomycin-resistant Enterococcus faecium and faecalis (VRE) remains a major complication among critically ill patients. A 26-year-old patient with 65% total body surface area burns (TBSA) was infected with several E. faecium strains during his admission that were resistant to vancomycin. Because chloramphenicol was the standard treatment at this time, this drug was initiated until, the organism was identified as E. faecium and reported as susceptible to quinupristin-dalfopristin. Given these data, it was then decided to discontinue the chloramphenicol therapy. Quinupristin-dalfopristin therapy resulted in initial reduction of fever and white blood cell counts that continued over the next 5 days. However, on day 7 of quinupristin-dalfopristin therapy, a return of fever and elevation of the white blood cell count was noted and a repeated E. faecium blood culture demonstrated sudden resistance to quinupristin-dalfopristin (Bauer-Kirby zone size <14 mm). Chloramphenicol was restarted and the patient improved slowly over a period of 16 days. Our indigenous VRE had limited exposure to quinupristin-dalfopristin in the recent past; however, resistance emerged with the first commercial use of this agent in our burn treatment center. High-dose chloramphenicol treatment did not appear to impair engraftment of cultured epithelial autografts (CEA) in this patient.

Levofloxacin-induced toxic epidermal necrolysis in an elderly patient.

Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) are mild-to-life-threatening adverse reactions that have been described after exposure to fluoroquinolones. No published reports, however, exist of exfoliative disease after treatment with levofloxacin. A 78-year-old woman with many medical problems, including chronic obstructive pulmonary disease, was treated with parenteral levofloxacin for community-acquired pneumonia. She was discharged with oral levofloxacin to complete an additional 3 days of treatment as an outpatient. Two days after completing this regimen, the patient developed a rash with blistering. The rash progressed to TEN in 7 days, and she was transferred to a burn treatment center. She was treated with fluid resuscitation, wound dressing, and antibiotics. Her condition improved, and she was discharged after 22 days. To our knowledge, this case is the first published report of levofloxacin-induced TEN.