Case of ehrlichiosis induced Guillain-Barre Syndrome in a 71 year-old female.

Guillain-Barre Syndrome (GBS) is a rare autoimmune demyelinating polyradiculoneuropathy that causes an ascending paralysis and flaccid weakness. Tick paralysis is a mimic of GBS as symptoms include generalized weakness and paralysis. However, symptom onset and timing as well as lab findings can distinguish between them. We present a case of a 71-year-old female who complained of generalized weakness and dizziness starting three weeks prior to admission. During that time, she had fevers and chills and a questionable insect bite. Her lab values indicated thrombocytopenia and elevated liver enzymes. PCR titers were positive for ehrlichiosis and she was started on doxycycline then discharged. She returned over a week later with worsening symptoms despite treatment. There was concern she may had Heartland or Bourbon virus but titers were negative. Her neurological exam showed numbness and areflexia in her lower extremities which progressed since her first encounter. She was given IVIG and her symptoms improved and recovered slowly. Although ehrlichiosis is not a common cause for GBS, the pathogenesis is like Lyme disease or Campylobacter jejuni. This patient had clinical symptoms that were like tick-borne illness yet as her disease progressed, it illustrated the need for an expanded differential diagnosis. There is very little literature about ehrlichia inducing GBS. It is important to keep a broad differential as sometimes common syndromes do not always come from common pathogens and with the COVID-19 pandemic having similar results, we are learning new things that may potentially be new standards in medical education.

Urine colorimetry for levofloxacin pharmacokinetics and personalized dosing in people with drug-resistant tuberculosis.

Background: Levofloxacin is a preferred drug for multidrug-resistant (MDR)-tuberculosis (TB) with bactericidal activity that correlates with the pharmacokinetic exposures of serum peak concentration (Cmax) and total area under the concentration time curve (AUC0-24). Pharmacokinetic exposures can be measured to personalize dosing to reach targets, but this practice requires venepuncture, chromatographic or mass spectrometry equipment, and technical expertise. We sought to demonstrate the accuracy of using urine colorimetry as a more feasible estimation of levofloxacin exposure. Method: A colorimetric method using bromocresol green was tested on spiked urine samples with levofloxacin measured using a spectrophotometer. This method was tested in urine samples of healthy volunteers given one 750 mg dose of levofloxacin with urine collected at 0-4 h, 4-8 h, and 8-24 h intervals, and concomitant serum samples were collected and analyzed by high-performance liquid chromatography. Validation of this assay was done in a cohort of people living with human immunodeficiency virus (PLWH), initiating a levofloxacin containing MDR-TB regimen. Results: Urine colorimetry was reproducible in spiked samples and the calibration was curve linear for levofloxacin concentrations ranging from 7.8 µg/ml to 250 µg/ml, with r = 0.98. In healthy volunteers, correlation between urine absorbance values and serum AUC0-24 was highest in urine collected between 4 and 8 h (r = 0.91, P = 0.01), yet in PLWH, urine collected between 0 and 4 h had highest correlation (r = 0.66, P = 0.05). The area under the receiver operating characteristics curve was >0.8 in the derivation, as well as the validation cohort for the urine absorbance values identifying people with total serum exposure below target. Conclusion: Urine colorimetry was highly sensitive in predicting target serum concentrations. Colorimetric methods to determine levofloxacin in urine may improve the feasibility of therapeutic drug monitoring and personalized dose adjustment in TB endemic settings.

Colonic mucormycosis in an immunocompetent patient with endocarditis.

Mucormycosis is a fatal opportunistic fungal infection. Rarely it can occur in immunocompetent patients. Here, we present a case of colonic mucormycosis in immunocompetent patients.

Efficacy of raltegravir, etravirine and darunavir/ritonavir for treatment-experienced HIV patients from a non-urban clinic population in the United States.

BACKGROUND: The regimen of raltegravir (RAL), ritonavir-boosted darunavir (DAR/r), and etravirine (ETR) for HIV treatment-experienced patients in a non-clinical trial setting in the rural/semi-urban United States had not been evaluated. OBJECTIVE: A retrospective cohort analysis was performed of adult patients prescribed the regimen from 2008 to 2013 at a HIV clinic serving such a population. RESULTS: In all, 51 patients met inclusion criteria including 15 with suppressed viral loads at regimen initiation. Of the 36 patients with detectable viral loads, 22 (61.1%) achieved a plasma HIV-1 RNA level < 50 copies/ml at 28 weeks and 17 maintained viral suppression at 56 weeks (50% of those surviving without death). Of 42 patients with long-term follow-up, mean of 216 ± 83 weeks following regimen initiation, 31 (73.8%) had viral suppression. Suppression was significantly more likely in those patients that maintained adherence. CONCLUSIONS: In a non-urban clinic population from the United States with considerable treatment experience, the combination of RAL, DAR/r, and ETR was well tolerated and resulted in viral suppression in those that maintained adherence. Future prospective studies may better define the role of such a regimen in the context of revised recommendations for first-line medications in the HIV treatment naïve.

Determination of plasma concentrations of levofloxacin by high performance liquid chromatography for use at a multidrug-resistant tuberculosis hospital in Tanzania.

Therapeutic drug monitoring may improve multidrug-resistant tuberculosis (MDR-TB) treatment outcomes. Levofloxacin demonstrates significant individual pharmacokinetic variability. Thus, we sought to develop and validate a high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection for levofloxacin in patients on MDR-TB treatment. The HPLC-UV method is based on a solid phase extraction (SPE) and a direct injection into the HPLC system. The limit of quantification was 0.25 µg/mL, and the assay was linear over the concentration range of 0.25-15 µg/mL (y = 0.5668x-0.0603, R2 = 0.9992) for the determination of levofloxacin in plasma. The HPLC-UV methodology achieved excellent accuracy and reproducibility along a clinically meaningful range. The intra-assay RSD% of low, medium, and high quality control samples (QC) were 1.93, 2.44, and 1.90, respectively, while the inter-assay RSD% were 3.74, 5.65, and 3.30, respectively. The mean recovery was 96.84%. This method was then utilized to measure levofloxacin concentrations from patients' plasma samples from a retrospective cohort of consecutive enrolled subjects treated for MDR-TB at the national TB hospital in Tanzania during 5/3/2013-8/31/2015. Plasma was collected at 2 hours after levofloxacin administration, the time of estimated peak concentration (eCmax) treatment. Forty-one MDR-TB patients had plasma available and 39 had traceable programmatic outcomes. Only 13 (32%) patients had any plasma concentration that reached the lower range of the expected literature derived Cmax with the median eCmax being 5.86 (3.33-9.08 µg/ml). Using Classification and Regression Tree analysis, an eCmax ≥7.55 µg/mL was identified as the threshold which best predicted cure. Analyzing this CART derived threshold on treatment outcome, the time to sputum culture conversion was 38.3 ± 22.7 days vs. 47.8 ± 26.5 days (p = 0.27) and a greater proportion were cured, in 10 out of 15 (66.7%) vs. 6 out of 18 (33.3%) (p = 0.06) respectively. Furthermore, one patient with an eCmax/minimum inhibitory concentration (MIC) of only 1.13 acquired extensively drug resistant (XDR)-TB while undergoing treatment. The individual variability of levofloxacin concentrations in MDR-TB patients from Tanzania supports further study of the application of onsite therapeutic drug monitoring and MIC testing.