Archive for the ‘Treatment’ Category

Probable Transfusion-Transmission of Babesiosis

The Brief case: Probable transfusion-transmitted babesiosis in a transplant recipient

Kitt E, Keaton AA, Graf EH.
Journal of Clinical Microbiology 54:2632–2634.

http://dx.doi.org/10.1128/JCM.00981-16

Case

A 3-year-old immunocompromised male who had been hospitalized for 7 months in the cardiac intensive care unit developed fever and tachycardia in December. He was prenatally diagnosed with hypoplastic left heart syndrome and received right ventricle to pulmonary artery conduit surgery days after delivery. Due to worsening right ventricular function, after a hemi-Fontan procedure, he received an orthotopic heart transplant at the beginning of his 3rd year of life.

His posttransplant course was complicated by multiple episodes of rejection, cytomegalovirus (CMV) pneumonitis, and several central-line-associated bloodstream infections. As a result of the rejection, necessitating plasmapheresis as well as frequent blood draws for management, which led to anemia, he received 36 packed red blood cell transfusions over the course of 7 months posttransplantation. These transfusions were evenly spaced, and he remained hospitalized during the 7 months.

At the time of the febrile episode, he was on caspofungin, trimethoprim-sulfamethoxazole, and ganciclovir. The subsequent diagnostic workup included multiple sets of blood cultures, a urine culture, and a CMV viral load analysis. He was started on vancomycin and cefepime while awaiting microbiologic results. Other pertinent test results included a complete blood count (CBC) with differential showing pancytopenia and an aspartate transaminase (AST) level of 200 U/liter (reference range, 20 to 60 U/liter), an alanine aminotransferase (ALT) level of 84 U/liter (reference range, 5 to 45 U/liter), and a C-reactive protein level of 3.1 mg/dl (reference range, 0 to 0.9 mg/dl), which increased to 7.1 mg/dl over 4 days.

On the 5th day of fever, another CBC with differential was ordered and was noted by the hematopathologist to contain intraerythrocytic parasites. Immediately, a blood smear with Giemsa stain (Harleco Giemsa stain; EMD Millipore, Billerica, MA, USA) was performed by the microbiology laboratory, yielding the definitive diagnosis. Babesia species with a parasitemia level of 18% was reported to the clinical team. Real-time PCR testing, performed by a reference laboratory, provided the species-level identity of Babesia microti. All other infectious workups were negative. The patient was started on azithromycin plus atovaquone due to the contraindications against treatment with quinidine (QT interval prolongation in a heart transplant recipient with declining heart function).

Three days later, clindamycin was added when his parasitemia level did not decline. He was also given an exchange transfusion on day 4 after diagnosis in an attempt to reduce his parasitemia. After 14 days of therapy, his parasitemia became undetectable and he completed 6 full weeks of therapy, at which time he remained aparasitemic. Since transfusion was the child’s only known risk factor for Babesia infection, a complete investigation into the blood products used was conducted, but the infectious unit/donor could not be definitively identified. Banked products from the organ donor were also tested, and it was determined that the heart transplant was not the source of the Babesia infection.

Category:

Babesia, research, Treatment

Lyme Disease: A Bioethical Morass

http://www.omicsonline.org/clinical-research-bioethics-abstract.php?abstract_id=81033

Abstract
“Primum non nocere”, “first do no harm” is a medical dictum based in antiquity. Yet, in nearly everything related to Lyme disease, it seems almost entirely disregarded. How ethical is it that we follow the guidelines of the CDC regarding diagnosis when those guidelines require erythema migrans that is clearly recognizable only in one (“bullseye rash”) of its multiple presentations? Further, how ethical is it that we are held to guidelines regarding a positive serology that is positive (at best) only 40% of the time? Another questionable ethical situation is the use of a bacteriostatic antibiotic that barely meets the MIC for Borrelia burgdorferi in its ordinarily prescribed regimen. It is also dependent on compliance which is a huge issue because of the gastrointestinal side effects. This antibiotic may clear the rash, but seemingly does little to prevent late findings of the disease. The sub lethal antibiotic dose can be important in the subsequent development of biofilms that lead to a chronic disease state. Lastly, how ethical is it that we have nearly abandoned our patient advocacy and permitted the insurance companies to dictate allowable treatment? And, in as much as Borrelia organisms were found in the brains of Alzheimer’s disease patients over 25 yrs ago and those spirochetes have recently been shown to produce biofilms, how ethical is it that we ignore research underpinning the pathogenesis of this disease? The intent of this work is to discuss how all aspects of Lyme disease (LD) are bioethically challenged. We include Alzheimer’s disease (AD) in the discussion because Lyme spirochetes have been found in, and cultured from, the brains of AD. This makes LD, in its presentation as AD, the equivalent of tertiary neurosyphilis with the only difference being a different spirochete.

 

Category:

Lyme, Testing, Treatment

News Story on Researcher Kim Lewis and Chronic Lyme

Published on Oct 25, 2016 by Sharon Crowley Fox News

Each year about 300,000 people in the United States will get Lyme disease, a tick-borne illness. The majority — about 90-percent — of those who get Lyme disease will take a short round of antibiotics and within a few weeks feel better. But doctors say 10 percent will develop long-term health problems known as post-treatment Lyme disease syndrome, or PTLDS.

Dr. Kim Lewis leads a Lyme disease research team at Northeastern University’s Anti-Microbial Discovery Center in Boston. He says doctors do not know what the difference between those people who will and will not develop PTLDS. The symptoms of PTLDS, also known as chronic Lyme disease, can be debilitating.

PTLDS brought Dr. Lewis and other researchers from all fields of science, medicine, and the environment together at conference in New York City at the Icahn School of Medicine at Mount Sinai. These experts are sharing what they are learning about fighting Lyme disease and its long-term side effects.

Dr. Lewis and his team of researchers in Boston are trying to solve problems on several fronts. He also hopes within the next year or two there will be a blood test available to determine if you get Lyme disease if you will be among the 10 percent likely to develop long-term problems. Knowing that would help doctors immediately prescribe a more aggressive antibiotic treatment.

Dr. Lewis says he and his team are testing a mixture of drugs already on the market being used for something else they believe will also work on solving the long-term effects of Lyme disease.

Category:

Lyme, Treatment

Of Rabbits and Men

rabbit-meadow-1280x1024

Tularemia is known as a rabbit disease which is spread to those who handle them including hunters and cooks; however, at the recent Lyme Disease Association 17th Annual Conference on Lyme and Tick-Borne Diseases, Timothy Lepore, MD, FACS, surgeon at Nantucket Cottage Hospital, explained that it is also a disease of those who work with the land such as landscapers and farmers, as well as those who get bit by a tick. There are cases reported in every state but Hawaii, and many other wild and domestic animals can be infected. The highest rates of infection are in Arkansas.

Tularemia first appeared in the United States in Massachusetts in 1937 after importing 30,000 to 40,000 rabbits per year from Europe. Importing came to an end in 1947.

http://columbia-lyme.org/patients/tbd_tularemia.html
Francisella tularensis, a gram negative, aerobic, pleomorphic, highly persistent intracellular pathogen, spread via the lymphatic system can cause fever, chills, headache, myalgia, extreme fatigue, glandular (swollen glands), oropharyngeal (sore throat, nausea, vomiting and diarrhea, abdominal pain and intestinal ulcerations), conjunctivitis, pneumonic (dry cough, respiratory difficulty and chest pain), ulceroglandular (skin ulcer at infection site) and can be septic and lethal. Symptoms typically develop within three or four days of inoculation but can take up to 10 days.

Tests: Tests for Tularemia are not widely available but direct examination of biopsy specimens or secretions by fluorescent antibody or Gram or histochemical stains are often helpful. F. tularensis can also be demonstrated microscopically with fluorescent-labeled antibodies. Antibodies are not typically present in the first ten days after exposure. Patient samples should come from sputum or pharyngeal washings, as the organism is not present in large numbers in blood. Polymerase chain reaction (PCR) tests can also be utilized. It is imperative that lab personnel take strong precautions as it is quite easy to become infected.

Treatment: Antibiotic therapy with Gentamicin (5mg/kg/day, IM or IV) or streptomycin (1 gm twice daily, IM). The recommended treatment period is 10 days. In vitro susceptibility studies indicate that quinolones and fluoroquinolones are also effective against F. tularensis, thus providing an additional option for physicians. Tetracyclines and chloramphenicol can also be used, but a higher rate of relapse is associated with these agents, as they are bacteriostatic rather than bactericidal. Thus, it is recommended that treatment with these medications be extended to 2-3 weeks. If treatment is initiated quickly the mortality rate for tularemia is around 1-2%; however, one-third of untreated patients will die, usually from pneumonia, meningitis or peritonitis.

http://www.idph.state.il.us/public/hb/hbtulare.htm
Transmission: Transmission can occur through the skin or mucous membranes when handling infected animals as well as through tick bite, contact with fluids from infected deer flies, mosquitoes or ticks, handling or eating undercooked rabbit, drinking contaminated water, inhaling dust from contaminated soil, and handling contaminated pelts or paws of animals. It can also be inhaled from infected hay, grain, or soil. Dr. Lepore had patients who contracted it from their pet dog who shook rain water on them after chewing on a dead rabbit, as well as from folks eating road kill, a person who held sick animals, and a gentleman who slept with his pet bunny.
http://www.siumed.edu/medicine/id/tularemia.htm
Tularemia, in aerosol form, is considered a possible bioterrorist agent that if inhaled would cause severe respiratory illness. It was studied in Japan through 1945, the USA through the 60’s, and Russia is believed to have strains resistant to antibiotics and vaccines. An aerosol release in a high population would result in febrile illness in 3-5 days followed by pleuropneumonitis and systemic infection with illness persisting for weeks with relapses. The WHO estimates that an aerosol dispersal of 50 kg of F. tularensis over an area with 5 million people would result in 25,000 incapacitating casualties including 19,000 deaths.

In a mass casualty situation – treat with oral agents for 14 days using Doxycycline (adults 100mg by mouth twice a day, children under 45kg 2.2 mg/kg by mouth twice daily) or Ciprofloxacin (adults 500mg, by mouth twice a day, children 15mg/kg by mouth twice a day).

Those performing autopsies should avoid bone sawing or any procedure likely to cause aerosolization and exposed people should wash with soap and water. In environmental contaminations use a 10% bleach solution for spraying and cleaning using alcohol 10 minutes after using bleach. There have been no reports of human to human transmission.

Category:

Ticks, Treatment, Tularemia

Study on Ceftriaxone

http://journal.frontiersin.org/article/10.3389/fmicb.2016.01744/abstract

Abstract

Although the majority of Lyme disease patients can be cured, at least 10-20% of the patients continue to suffer from persisting symptoms such as fatigue, muscular and joint pain, and neurologic impairment after standard 2-4 week antibiotic treatment. While the causes for this post-treatment Lyme disease symptoms are unclear, one possibility is due to B. burgdorferi persisters that are not effectively killed by current antibiotics such as doxycycline or amoxicillin used to treat Lyme disease. A previous study showed that four rounds of ceftriaxone pulse dosing treatment eradicated B. burgdorferi persisters in vitro using a relatively young late log phase culture (5 day old).

In this study, we investigated if ceftriaxone pulse dosing could also eradicate B. burgdorferi persisters in older stationary phase cultures (10 day old) enriched with more resistant microcolony form of persisters. We found that ceftriaxone pulse dosing could only eradicate planktonic log phase B. burgdorferi spirochetal forms and round body forms but not more resistant aggregated biofilm-like microcolony persisters enriched in stationary phase cultures. Moreover, we found that not all drugs are suitable for pulse dosing, with bactericidal drugs ceftriaxone and cefuroxime being more appropriate for pulse dosing than bacteriostatic drug doxycycline and persister drug daptomycin.

We also showed that drug combination pulse dosing treatment was more effective than single drug pulse dosing. Importantly, we demonstrate that pulse dosing treatment impaired the activity of the persister drug daptomycin and its drug combination against B. burgdorferi persisters and that the most effective way to kill the more resistant biofilm-like microcolonies is the daptomycin/doxycycline/ceftriaxone triple drug combination without pulse dosing. Our findings indicate pulse dosing may not always work as a general principle but rather depends on the specific drugs used, with cidal drugs being more appropriate for pulse dosing than static or persister drugs, and that drug combination approach with persister drugs is more effective at killing the more resistant microcolony form of persisters than pulse dosing.

These observations may have implications for more effective treatment of Lyme disease. Future studies are required to validate these findings in animal models of B. burgdorferi persistence.

http://journal.frontiersin.org/article/10.3389/fmicb.2016.01744/abstract

Free, full provisional text (pdf file, 2.31 MB):
http://journal.frontiersin.org/article/10.3389/fmicb.2016.01744/pdf

Category:

Lyme, research, Treatment