Going from treatment dose to prophylaxis

[Tattoomom]

My 4 year old daughter is on Augmentin 600mg 2 x daily.

 

My 9 year old dd is on Omnicef (allergic to Penicillins) 250mg 2 x daily.

 

My 11 year old ds is on Augmentin tabs 875mg 2 x daily.

 

 

My questions are:

 

How do you know when it's time to back off the antibiotics? And when you do back off, how much is enough???

[beeskneesmommy]

My 6 yr. old has been on abx for 3 yrs. strraight and a hefty protocol of both Augmentin and Azith since 7/2011. I guess it depends upon what your specialist says and how the kiddo is doing. This current protocol really helped a lot. He had IVig 9 wks. ago for the 1st time and we decided, despite that fact that he is doing very well, to keep the abx on board until spring in order to protect him. I, personally, would not make the decision to back off without my specialist working along side me, as I would want to titrate down slowly, each time watching for a week or 2 to see if any PANDAS symptoms start to return...

[Tattoomom]

Well, my "specialist" is our Pediatrician. She's been very helpful to us, but is not a PANDAS doctor by any means. She wants to see us wean down to a preventative dose, but I have no idea how. We haven't been on steady abx long (Augmentin a couple months, before that was on Zithromax a couple months and before that Amoxicillin a couple months) We yo-yo'd a lot, trying to find what works. She's a BAD case. She's also on Zoloft and Tenex.

 

My son has only been on Augmentin a few weeks, and the difference is amazing!!!! He takes Zoloft as well.

 

My older daughter is still struggling some. I wish she could take Augmentin...

 

I know it depends on the individual child and case, but I wish there was something I could show our Pediatrician about long term abx benefits. Any studies on prophalxsis dosing? Anything I can email her or print out would be great!

[Mayzoo]

Here is an article about Prophylaxis, but the abx they used were zith and/or penicillin. Still it is about prophylaxis so I hope it helps (sorry I did not have time to read them):

 

NIMH article

 

Here is another article in full since you may have to be a member at medscape to see it:

 

PANDAS in Children -- Current Approaches

 

Richard P Barthel, MD

 

Faculty and Disclosures

 

CME/CE Released: 12/11/2002; Valid for credit through 12/11/2003

CME/CE Information

Introduction

 

Postinfectious autoimmune disorders in response to Streptococcus infections were confirmed in the 1950s.[1] Rheumatic fever (RF) was the prototype disorder and Sydenham chorea (SC) was identified, not only as a criteria for the diagnosis of RF but also as a stand-alone manifestation of the potential for a central nervous system autoimmune response. SC can have a mix of both motor and psychiatric manifestations, including hyperactivity, mood lability and, in severe cases, psychosis. Behavioral symptoms often precede the motor manifestations and can include obsessive-compulsive features. On average, SC lasts about 6 months.[2]

Defining the PANDAS Subgroup

 

Swedo and colleagues[3] first proposed that some cases of childhood-onset obsessive-compulsive disorder (OCD) might be, like SC, a post-step disorder of immune character. They coined the acronym PANDAS to identify the occurrence of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. This is a disorder of prepubertal children with sudden and dramatic onset of OCD post-streptococcal infection. Dr. Susan Swedo,[4] from the Pediatric Developmental and Neuropsychiatry branch of the National Institute of Mental Health (NIMH), presented that these children have a remarkably episodic course with remitting and relapsing OCD symptom severity. Her criteria for a PANDAS presentation also require the presence of associated neurologic problems. These are usually "choreiform" movements, which, by definition, are not full-blown SC. In fact, these are often subtle movements. They do not interfere with voluntary motor control and may only be elicited with careful observation of the extended hand/fingers. Such movements were present in 25 of 26 children seen during an exacerbation of their OCD symptoms in the early studies at NIMH.[5] The exacerbations must also have a temporal relationship to repeated Group A beta-hemolytic Streptococcus (GABHS) infections.

 

Dr. Swedo reported that there was an initial sense by clinicians that a larger spectrum of psychiatric disorders (eg, attention deficit/hyperactivity disorder, autism, anorexia nervosa) might also be placed under the PANDAS rubric. However, she feels strongly that this subgroup classification should be reserved, at this time, for OCD and tic disorders. The full Diagnostic and Statistical Manual of Mental Disorders, 4th edition[6] criteria for these disorders must be met before PANDAS should even be considered.

 

Current thinking, according to Dr. Swedo, does allow for "possible" PANDAS to be considered if there is a child with a prepubertal onset relapsing/remitting OCD and/or tic disorder. This is true only if the neurologic problems and relationships to GABHS infections have not been fully explored or documented. She feels that knowledge of the PANDAS associations must encourage clinicians to search for the "missing" criterion with each exacerbation. Thus, the pursuit of laboratory confirmation of the GABHS infection should be undertaken.

 

Dr. Harry Hill,[7] Infectious Disease specialist and Streptococcus researcher at the University of Utah School of Medicine, reported that the current "rapid" streptococcal screens used in most clinics are perfectly acceptable for proving the presence of the Streptococcus if positive. However, if the rapid screen is negative, this is not a true indication of the absence of infection. A full plate culture needs to be done. Retrospective assessment of exposure to Streptococcus will require the use of immune markers (eg, AntiStreptolysin O [ASO], Anti-Dnase-. It should be recognized that the ASO titer is not elevated at the time of acute infection. It is an antibody response peaking in 2-4 weeks. An elevated level can last for 6-12 months before, barring reinfection or other complications, it returns to baseline. Criteria for true diagnostic titers require both acute and convalescent specimens. Diagnostic levels (reported in Todd units) can vary among labs and are age-dependent. Anti-Dnase-B (also known as Streptodornase) is less discriminating (20% of the healthy population have elevated levels). Since these titers rise more slowly and remain elevated longer, they may be helpful in some cases. Franciosi stated that paired titers showing a 4-fold rise should be considered positive.[8] He also noted that combined testing, using both tests along with the Antihyaluronidase titer as a Streptococcus "panel," is reported to be 90% confirmatory of a Streptococcus infection.

Genetic Risks?

 

There does appear to be a genetic susceptibility to poststreptococcal autoimmune disorders, including RF and SC. Previous research focused on the D8/17 antibody. This monoclonal antibody identifies B-cell antigens present in all patients with RF, where it has been studied extensively.[9] Dr. Tanya Murphy, of the University of Florida, noted that, unfortunately, it has been found to be rather nonspecific in neuropsychiatric disorders. In addition, she and Dr. Hill[7] both considered the reliability and validity of the assay to be suspect. The lack of usefulness of this laboratory marker for any diagnostic purpose in suspected childhood PANDAS was reinforced by Dr. William McMahon.[10] Therefore, currently, it seems to have no place in the assessment of PANDAS in children.

 

Dr. McMahon, Child Psychiatrist and Geneticist at the University of Utah, studied the broader area of general familial genetic risk. He looked for the presence of OCD and tic disorders in families involved in the current RF resurgence in his region. (Dr. Hill[7] reminded clinicians that the incidence of RF was in significant decline through the mid-1980s but is now more prevalent in some areas [eg, intermountain region of the western United States] for reasons that are poorly understood.) His goal was to see if Tourette disorder (TD) or OCD was associated with the SC criteria for RF. In a pilot survey of 100 families, he found almost 4 times as many SC probands (22%) had relatives with TD/tics or OCD than non-SC RF patients (6%). He feels this supported an as yet unidentified "common genetic risk factor." This should prompt clinicians to be careful about the family history of children who are suspected of PANDAS.

PANDAS -- Management and Treatment

 

The recent report by Murphy and Pichichero[12] is the first evidence that it may be possible to identify children with potential PANDAS more acutely. This report, from a vigilant pediatric practice, identified 12 children with new-onset PANDAS-like presentation over 3 years. All had GABHS infection, sometimes mild in classical (ie, tonsillitis/pharyngitis) presentation, with abrupt appearance of OCD symptoms. (Intriguingly, in this study, there was also the new onset of daytime urinary urgency/frequency in 7 of 12 patients.) If antibiotic treatment was successful in eradicating the streptococcal infection, the OCD symptoms also resolved. Recurrence of OCD symptoms, with recurrent GABHS infection, was found in 6 of 12 children. Appropriate treatment again relieved the OCD symptoms if the infection was managed. Given the success of antibiotic treatment in the prevention of 90% of RF and 50% of acute poststreptococcal glomerulonephritis, this study supports the vigorous inquiry and treatment of GABHS infections as a potential prevention effort of PANDAS as well.[7]

 

Treatment for the PANDAS subgroup of children with OCD is not different from treatment for others with this diagnosis. Dr. Murphy recommended the use of combined behavioral therapies and low doses of selective serotonin reuptake inhibitors (SSRIs) with rapid taper to clinically effective levels as reported in the literature.[9,11] Controversies arise when treatment is less than ameliorating or if the exacerbations are problematic.

 

Perlmutter and colleagues[13] have published the results of their attempts at immunomodulatory therapy with more severe and treatment resistant children with PANDAS. Part of the NIMH group studying these disorders, they found that both intravenous pooled immunoglobulin (IVIG) and plasma exchange (PE) were successful in reducing OCD and other behavioral symptoms. Gains were maintained for up to 12 months. PE was reported to produce more rapid onset of change (< 2 weeks) and had "more striking" improvements in OCD.[5] Given the complications/risks of IVIG, this is not recommended currently by Dr. Swedo as a treatment. She agreed with the NIMH statement[14] that this is an experimental intervention. Dr. Swedo did report that she feels that children with more severe symptoms should be considered for therapeutic plasma exchange if other interventions have failed and there is a clinical exchange team available who has experience with young children.[4] She indicated that families need to know this is an area of ongoing research and that PE and other modalities for treatment are under continuing study at NIMH.

 

An active question in that research is the effect of prophylactic antibiotics (PAbx) in children with PANDAS. This is another difficult area for clinicians. PAbx are routine for those with carditis resulting from RF, and their success in prevention of further heart damage is a clear indicator of the relationship between GABHS and RF. Early studies[15] of PAbx in children with PANDAS have been complicated by poor compliance and the dilemmas of placebo treatment. Since study children will be at risk for GABHS infections through the study period, ethically they require treatment. Dr. Swedo presented early indications of clinical directions from unpublished data[4] but felt it was "too early" to recommend this. Her strongest concern was how long to continue antibiotics if they are started. This and other unanswered questions will continue to guide the study of PANDAS.

 

Finally, the question of how much of "typical" OCD may have its genesis in postinfectious etiology is a tantalizing one. Given the interest of psychiatry and child psychiatry in finding clear etiologies for many disorders, the possibilities of viral and bacterial contributions to currently poorly understood disorders and their exacerbations make the evolving PANDAS story a model for all clinicians to watch.

Clinical Correlation

 

An 8-year-old girl presents to her MD's office with sudden onset of frequent hand washing with distress about "germs"; she has a sore throat. Mother is known to have struggled with OCD and dad has a tic disorder. Mom is anxious about PANDAS!

 

The patient should be screened with a "rapid" strep test: if positive, she should be treated with appropriate antibiotics; if negative, a plate culture should be done. In either case, the family should be counseled about appropriate behavioral approaches to the girl's obsessive-compulsive symptoms. If mother has a cognitive-behavioral therapist in place, a contact to that clinician is appropriate. Appropriate follow-up of culture, treatment to resolution of any infection, and tracking of OCD symptoms is indicated.

 

Four weeks later, the girl is more significantly involved with obsessions and compulsions about germs. Contamination fears interfere with comfort at school and home. Cognitive-behavioral therapy principles have been initiated with some success. Mother has benefited from fluvoxamine and feels her daughter will also.

 

Referral to a clinician skilled with the diagnosis and SSRI treatment of OCD in children is appropriate, and formal cognitive-behavioral therapy must be considered.

 

Six weeks later, she has multiple severe obsessive-compulsive anxieties and evidence of "psychotic" beliefs. She is sleeping poorly and eating is constricted due to her fears. After diagnosis of OCD, there was initial positive response to the medication/therapy trial, but this recently deteriorated.

 

The patient should be cultured again, and treated as appropriate. If positive, a search for a Streptococcus "carrier" in the family should be made. If negative, therapeutic plasma exchange might be considered. Consultation to the PANDAS group at NIMH, or other local experts, about this treatment and the potential usefulness of prophylactic antibiotics should be sought.

References

 

Berrios X, del Campo E, Guzman B, Bisno AL. Discontinuing rheumatic fever prophylaxis in selected adolescents and young adults. A prospective study. Ann Intern Med. 1993;118:401-406.

Murphy T, Goodman W. Genetics of childhood disorders: XXXIV. Autoimmune disorders, part 7: D8/17 reactivity as an immunological marker of susceptibility to neuropsychiatric disorders. J Am Acad Child Adolesc Psychiatry. 2002;41:98-100.

Swedo S, Leonard HL, Garvey M, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection: clinical descriptions of the first 50 cases. Am J Psychiatry. 1998;155:264-271.

Swedo S. Pediatric autoimmune neuropsychiatric disorders associated with strep infections (PANDAS). Program and abstracts of the American Academy of Child and Adolescent Psychiatry 49th Annual Meeting; October 22-27, 2002; San Francisco, California. Symposium 26.

Swedo SE. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Mol Psychiatry. 2002;7(suppl 2):S24-25.

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, fourth edition. Washington, DC: American Psychiatric Association; 1994.

Hill H. Group A streptococcal infections and the pathogenesis of acute rheumatic fever. Program and abstracts of the American Academy of Child and Adolescent Psychiatry 49th Annual Meeting; October 22-27, 2002; San Francisco, California. Symposium 26.

Franciosi R. Laboratory Services Directory -- Vol. 2, Children's Hospital of Wisconsin. Hudson, Oh: Lexi-Comp Inc; 1992.

Murphy T. Tics, compulsions and strep throat. Program and abstracts of the American Academy of Child and Adolescent Psychiatry 49th Annual Meeting; October 22-27, 2002; San Francisco, California. Institute 1.

McMahon W. Genetics of TD and RF: do they overlap? Program and abstracts of the American Academy of Child and Adolescent Psychiatry 49th Annual Meeting; October 22-27, 2002; San Francisco, California. Symposium 26.

Riddle M, Reeve EA, Yaryura-Tobias JA, et al. Fluvoxamine for children and adolescents with obsessive-compulsive disorder; a randomized, controlled, multicenter trial. J Am Acad Child Adolesc Psychiatry. 2001;40:222-229.

Murphy M, Pichichero M. Prospective identification and treatment of children with pediatric autoimmune neuropsychiatric disorder associated with group A streptococcal infection (PANDAS). Arch Pediatr Adolesc Med. 2002;156:356-361.

Perlmutter S, Leitman SF, Garvey MA, et al. Therapeutic plasma exchange and intravenous immunoglobin for obsessive-compulsive disorder and tic disorders in childhood. Lancet. 1999;354:1153-1158.

Plasma exchange and intravenous immunoglobin lack proven benefit and carry risk for children with PANDAS, Tourette's syndrome, or OCD. Available at http://www.nimh.nih.gov/events/pandaalert.cfm. Accessed November 15, 2002.

Garvey MA, Perlmutter SJ, Allen AJ, et al. A pilot study of penicillin prophylaxis for neuropsychiatic exacerbations triggered by streptococcal infections. Biol Psychiatry. 1999;45:1564-1571.

[Tattoomom]

Thank you so much for the replies!

 

I was hoping to hear what others are on, specifically how much (how many times per day/week?) and how long (months, YEARS?)

[Teri]

Just to chime in with medication info. We are exactly one year into this PANDAS battle. DD 6 was on Azithromycin on and off for about 4 months (prescribed by Pediatrician). Two months into the battle we saw symptoms creep back as soon as she was off RX. Pediatrician was treating conservatively - was dosing Azithromycin 5 days on - 5 days off. Dd is allergic to amoxicillin & omnicef. We sought a specialist because we thought we needed a more aggressive treatment plan.

 

DD has now been on Azithromycin 200mg daily for 9 months. She is also on Cipro 100mg 2x per day for the past 3 months to treat Lyme/Bartonella . She has also been on Diflucan or Lamisil to treat yeast infections during this time.

 

 

Teri