Jacques Simkins

Successful Treatment of Carbapenemase-Producing Pandrug-Resistant Klebsiella pneumoniae Bacteremia

ABSTRACT New antibiotic options are urgently needed for the treatment of carbapenem-resistant Enterobacteriaceae infections. We report a 64-year-old female with prolonged hospitalization following an intestinal transplant who developed refractory bacteremia due to a serine carbapenemase-producing pandrug-resistant isolate of Klebsiella pneumoniae. After failing multiple antimicrobial regimens, the patient was successfully treated.

Left ventricular assist device exchange for persistent infection: a case series and review of the literature

Left ventricular assist device (LVAD) exchange for control of infection may be an option for the treatment of persistent and severe infections of the LVAD. Data are limited regarding the indications for device exchange, methods for exchanging infected devices, post‐exchange antimicrobial management, and outcomes of such patients. We report a series of cases in which an exchange was performed for persistent LVAD infection, review the literature on LVAD exchange and surgical techniques for these infectious complications, and suggest management strategies from a multidisciplinary perspective.

Native valve endocarditis caused by rapidly growing mycobacteria: Case report and review of the literature

Rapidly growing mycobacteria (RGM) are included in group IV of Runyon’s classification for mycobacteria [1]. Out of the more than 40 species of RGM, only few have clinical relevance. Those with the most significance for human pathology belong to the M. fortuitum, M. chelonae-abscessus, and the M. smegmatis groups [1]. Endocarditis caused by RGM has been reported largely in prosthetic cardiac valves [2]. Native Cardiac Valve Endocarditis caused by these organisms is extremely rare. We describe a case of endocarditis of a native valve caused by M. abscessus.

Twelve-week rifapentine plus isoniazid versus 9-month isoniazid for the treatment of latent tuberculosis in renal transplant candidates

Background Renal transplant candidates (RTC) with latent tuberculosis infection (LTBI) are at significant risk for tuberculosis reactivation. Twelve-week rifapentine (RPT)/isoniazid (INH) is effective for LTBI but clinical experience in RTC is scarce. Methods We conducted a retrospective study of RTC with LTBI treated with either 12-week RPT/INH or 9-month INH from March 1, 2012, through February 28, 2014. We evaluated both groups for differences in rates of treatment completion, monthly follow-up visit compliance, transaminase elevations, and adverse reactions leading to discontinuation of LTBI treatment. The utility of weekly reminders was also evaluated in the 12-week regimen. Direct observed therapy was not performed in our study. Results Of 153 patients, 43 (28%) and 110 (72%) were started on 12-week RPT/INH and 9-month INH, respectively. The treatment completion and monthly follow-up visit compliance rates were higher in the 12-week RPT/INH group (40 [93%] vs 52 [47%], P < 0.001) and (11/40 [28%] vs 13/104 [13%], P = 0.03), respectively. Transaminase elevations were not observed in the RPT/INH group, but occurred in 6 (5%) of the INH group. There were no differences in adverse reactions leading to discontinuation of LTBI treatment. Conclusions Twelve-week RPT/INH appears to be an excellent choice for LTBI in RTC. It has a higher treatment completion rate and causes less transaminase elevations, and weekly reminders may be an alternative when direct observed therapy is not feasible.

The use of brincidofovir for the treatment of mixed dsDNA viral infection.

Double-stranded DNA (dsDNA) viral infections constitute a major complication following solid organ and stem cell transplantation. Few therapeutic options are currently available for the treatment of such infections in highly immunocompromised hosts. Brincidofovir is an oral investigational drug with broad antiviral activity against dsDNA viruses in vitro, but clinical experience is limited. Here we report a young female who developed a mixed infection with adenovirus, cytomegalovirus, Epstein-Barr virus and BK polyomavirus after an allogeneic stem cell transplant, and was successfully treated with brincidofovir.

Intravenous Fosfomycin Treatment for Carbapenem-Resistant Klebsiella pneumoniae in the United States

We read with interest the report by Kyle et al on the use of an oral fosfomycin-containing antibiotic regimen for the treatment of refractory carbapenem-resistant Klebsiella pneumoniae (CRKP) bacteremia. They reported a stem cell transplant recipient with septic shock caused by CRKP, in whom sterilization of blood cultures was only achieved after addition of high-dose oral fosfomycin (9 g orally, every 8 hours), with a successful outcome. Nonetheless, oral administration of antibiotics for the treatment of bacteremia is suboptimal in critically ill patients and should only be considered as a desperate measure. Although not available in the United States, intravenous (IV) fosfomycin has been used in Europe for CRKP with promising results. We would like to expand the observations from Kyle et al by reporting a patient with refractory CRKP bacteremia in whom sterilization of blood cultures was rapidly achieved after addition of IV fosfomycin. A 45-year-old woman underwent orthotopic liver transplant for cirrhosis secondary to nonalcoholic steatohepatitis. The posttransplant course was complicated by graft failure and prolonged stay in the intensive care unit; during this time, she was exposed to cefepime, piperacillin/tazobactam, meropenem, colistin, and tigecycline. On posttransplant day 149, she developed bowel ischemia and septic shock. Peritoneal fluid and blood cultures were positive for CRKP resistant to colistin (minimum inhibitory concentration [MIC] = 12 μg/mL) and tigecycline. She was initially treated with extended-infusion meropenem (1 g IV every 8 hours) and amikacin (7.5 mg/kg IV every 24 hours) without resolution of bacteremia. Because of hemodynamic instability, she was not considered a surgical candidate and efforts were made to maximize her medical therapy. One week later, colistin (2.5 mg/kg IV every 12 hours) and rifampin (600 mg IV every 24 hours) were added. Her cultures cleared on this regimen, but she had recurrent bacteremia 96 hours later. The CRKP isolate was fosfomycin susceptible (MIC = 16 μg/mL). IV fosfomycin was purchased from Europe and arrived at our institution 10 days later (after a 3-day delay in customs). On posttransplant day 173, fosfomycin (8 g IV every 8 hours) was started. Blood cultures became negative within 24 hours. Although hypokalemia is a potential side effect of fosfomycin, her lowest potassium level was 3.5 mmol/L (normal: 3.6-5 mmol/L) while on fosfomycin therapy. Unfortunately, on posttransplant day 179, the patient succumbed to Candida parapsilosis fungemia and multiorgan failure. This case, along with previous reports, suggests that fosfomycin is a safe and potentially useful antibiotic option for the treatment of serious infections caused by multidrug-resistant CRKP. After more than 40 years of its discovery, only the oral form of fosfomycin—approved by the Food and Drugs Administration (FDA) for uncomplicated urinary tract infections—is widely used in the United States. The poor bioavailability of oral fosfomycin (approximately 37%) limits its use in critically ill patients, particularly those with abdominal sepsis. When needed, IV fosfomycin has to be imported from Europe (from pharmaceutical companies such as Nordic Pharma in the United Kingdom and InfectoPharm in Germany) after an emergency investigational new drug application is approved by the FDA. This imposes significant delays that jeopardize the timely initiation of effective antibiotic therapy. Until newer and more effective antibiotics become available for the treatment of CRKP, we strongly feel that the availability of IV fosfomycin is urgently needed in the United States.

Solid organ transplant antibiograms: an opportunity for antimicrobial stewardship

OBJECTIVES We aimed to compare the antimicrobial susceptibility percentages in blood and urine bacterial isolates recovered from solid organ transplant (SOT) recipients with those reported in the hospital-wide antibiogram. METHODS Retrospective review of the antimicrobial susceptibilities of bacterial isolates recovered from SOT recipients at a 1550-bed hospital over a 2-year period. Antibiograms were categorized by anatomic site (blood and urine). Percentage of bacterial susceptibilities to specific antibiotics were compared with the hospital-wide antibiogram. RESULTS A total of 1889 unique cultures were identified. Blood and urine isolates of Escherichia coli, Klebsiella pneumonia and Pseudomonas aeruginosa had significantly lower susceptibility to first and second line antibiotics compared to the hospital-wide antibiogram. CONCLUSION Significant differences in susceptibilities between isolates from blood and urine cultures from SOT recipients and the hospital-wide antibiogram were found. A population-based strategy for the development of antibiograms specific for this group of high-risk patients could better guide appropriate empiric antimicrobial selection.

Pretransplant CD4 Count Influences Immune Reconstitution and Risk of Infectious Complications in Human Immunodeficiency Virus-Infected Kidney Allograft Recipients.

In current practice, human immunodeficiency virus–infected (HIV+) candidates with CD4 >200 cells/mm3 are eligible for kidney transplantation; however, the optimal pretransplant CD4 count above this threshold remains to be defined. We evaluated clinical outcomes in patients with baseline CD4 >350 and <350 cells/mm3 among 38 anti–thymocyte globulin (ATG)–treated HIV‐negative to HIV+ kidney transplants performed at our center between 2006 and 2013. Median follow‐up was 2.6 years. Rates of acute rejection and patient and graft survival were not different between groups. Occurrence of severe CD4 lymphopenia (<200 cells/mm3), however, was more common among patients with a baseline CD4 count 200–349 cells/mm3 compared with those transplanted at higher counts (75% vs. 30% at 4 weeks [p = 0.04] and 71% vs. 5% at 52 weeks [p = 0.001], respectively, after transplant). After adjusting for age, baseline CD4 count of 200–349 cells/mm3 was an independent predictor of severe CD4 lymphopenia at 4 weeks (relative risk [RR] 2.6; 95% confidence interval [CI] 1.3–5.1) and 52 weeks (RR 14.3; 95% CI 2–100.4) after transplant. Patients with CD4 <200 cells/mm3 at 4 weeks had higher probability of serious infections during first 6 months after transplant (19% vs. 50%; log‐rank p = 0.05). These findings suggest that ATG must be used with caution in HIV+ kidney allograft recipients with a pretransplant CD4 count <350 cells/mm3.

Pulmonary embolism in patients with acquired immunodeficiency syndrome presenting with clinical picture of Pneumocystis jiroveci pneumonia: Report of two cases

cerebral malignancies. We therefore feel convinced that this patient had ADEM, supported by the clinical response to corticosteroid therapy. At the time of presentation the patient had already fully seroconverted and there is no negative HIV test available within the previous 6 months. Therefore, the patient does not strictly fulfil the definition of primary HIV infection, namely detectable HIV-RNA or p24-antigen concomitant with negative or inconclusive HIV serology, or alternatively, evidence of seroconversion within the last 6 months [10]. However the clinical history with sexual exposure followed within 4 to 5 weeks by a febrile illness and subsequently after 1 month a positive HIV test with very high viral loads in both plasma and CSF as well as high CD4 count is fully compatible with and highly suggestive of primary HIV infection and very recent seroconversion. We therefore believe that this patient did have ADEM triggered by primary HIV infection, although it cannot be excluded that the patient had chronic HIV infection and ADEM caused by another infectious agent. In conclusion, we suggest that ADEM might be a possible, although rare, manifestation of primary HIV infection, and that ADEM should be considered among the multiple differential diagnoses in an HIV-infected patient presenting with neurological symptoms. References

Screening for Zika virus in deceased organ donors in Florida

Zika virus (ZIKV) cases have been detected across the United States (US) and locally acquired cases have been reported in Florida. Currently, there are no ZIKV screening guidelines and no data on the incidence among organ donors in the US. This retrospective study was conducted at Jackson Memorial‐Miami Transplant Institute. Positive ZIKV tests in local deceased organ donors were investigated from 6/2016 to 1/2017. We evaluated demographics and risk factors for ZIKV infection among organ donors and transplant outcomes among recipients of donors with positive ZIKV testing. One hundred forty‐two donors were analyzed. Ten percent had traveled to ZIKV‐endemic countries and 19% had outdoor occupations. Only 3% had positive ZIKV IGG. None had a positive ZIKV IGM or PCR. ZIKV‐positive donors were more likely to have traveled to ZIKV‐endemic countries (50% vs. 9%, P = .05). The kidneys from a ZIKV‐positive donor were transplanted in our hospital with no 6‐month rejection, graft failure, or death in the recipients. Our study demonstrated a low prevalence of ZIKV among deceased donors in our community. Despite local ZIKV transmission, ZIKV was more common in donors who traveled to ZIKV‐endemic countries. This cohort demonstrated excellent outcomes in recipients of ZIKV IGG‐positive donors. However, larger studies are needed.