REVIEW The Potential of Osteopathic Manipulative Treatment in Antimicrobial Stewardship: A Narrative Review Donald R. Noll, DO Financial Disclosures: The contemporary management of infectious diseases is built around anti­ None reported. microbial therapy. However, the development of antimicrobial resistance Support: None reported. threatens to create a post–antibiotic era. Antimicrobial stewardship at­ Address correspondence to tempts to reduce the development of antimicrobial resistance by improving Donald R. Noll, DO, their appropriate use. Osteopathic manipulative treatment as an adjunctive Professor of Medicine, Department of Geriatrics treatment has the potential for enhancing antimicrobial stewardship by en­ and Gerontology, hancing the human immune system, shortening the duration of antimicro­ New Jersey Institute bial therapy, reducing complications, and improving treatment outcomes. for Successful Aging, Rowan University School The present article reviews the evidence published in the literature since this of Osteopathic Medicine, unique treatment approach was first developed more than 100 years ago. 42 E Laurel Rd, Suite 1800, Stratford, NJ 08084-1338. The evidence suggests that adjunctive osteopathic manipulative treatment has great potential for enhancing antimicrobial stewardship and should be E-mail: [email protected] further investigated. Submitted J Am Osteopath Assoc. 2016;116(9):600-608 January 27, 2016; doi:10.7556/jaoa.2016.119 revision received March 13, 2016; accepted April 13, 2016. here are 2 strategies for treating patients with infectious disease. The first is to target the organism with an appropriate antimicrobial agent. In 1907, Paul Ehrlich developed his “magic bullet” arsphenamine (Salvarsan) and thus began the mod- T 1 ern antibiotic era. Since then the number of safe and effective antimicrobials has greatly increased1 so that today the treatment of patients with infectious disease is built around the use of antimicrobials.2 The second strategy is to support and enhance the human immune system so that the body will heal itself. Supportive care interventions fall into the latter category as they stabilize the patient long enough for the human immune system to mount an effective defense. Examples of supportive care interventions include administration of intravenous fluids, management of comorbidities, surgical drainage of abscesses, vaccina- tion, nutritional support, incentive spirometry, chest physiotherapy, and early mobilization. Antimicrobial therapy is so central to contemporary management of infectious diseases that all other interventions are considered to be adjunctive and have been given relatively little attention. Concerns are growing about antimicrobial resistance and are triggering calls for in- creased antimicrobial stewardship.2-4 The World Health Organization report on global anti- microbial resistance states that a post–antibiotic era—in which common infections and minor injuries can kill—is far from being an apocalyptic fantasy but is instead a very real possibility for the 21st century.5 Antimicrobial stewardship seeks to optimize the appropriate use of antibiotics with the goal of minimizing the development of antimicrobial resistance.3,6 Antimicrobial stewardship programs are formal efforts to avoid the overuse and misuse of 600 The Journal of the American Osteopathic Association September 2016 | Vol 116 | No. 9 REVIEW antibiotics.7 Strategies for enhancing antimicrobial stew- tained by collecting serum leukocytes and measuring ardship include surveillance for antimicrobial resistance; the average number of bacilli ingested by 100 leuko- improved use through education, clinical practice guide- cytes. His study design was a simple collection of lines, and policy; communication training; and enhanced baseline blood samples, mechanical stimulation of the laboratory testing, including the use of biomarkers to liver and spleen, and then collection of posttreatment confirm infection.3,6 One intervention not discussed in blood samples at various times after treatment.17 A these systematic reviews3,6 that has the potential to en- contemporary statistical analysis of his raw data hance antimicrobial stewardship is osteopathic manipula- (Table) suggests that liver and splenic stimulation does tive treatment (OMT). increase the phagocytic index over baseline for the first When OMT was first developed more than 100 years 2 hours after treatment. In the 1930s, Yale Castlio, DO, ago, infectious diseases were the dominant cause of mor- and Louise Ferris-Swift, DO, studied the effect of the bidity and mortality.4 It was the death of his 3 children splenic pump technique on individuals hospitalized for from an infectious disease that was a major impetus for various infectious diseases.18 They collected baseline Andrew Taylor Still, MD, DO, to develop OMT.8 In his blood samples on 100 individuals, applied the splenic autobiography, Still attributed the deaths to spinal men- pump technique, and then drew 2 posttreatment blood ingitis but later blamed the deaths of his 3 children on a samples at 7 different time intervals, allowing for contaminated water supply.8,9 Many OMT techniques paired comparisons of 25 or 50 individuals. A contem- were created specifically to treat patients with infections, porary analysis19 of their raw data showed that the regardless of the cause.10 Early osteopathic physicians splenic pump modestly increased serum white blood (ie, DOs) dreamed of defeating all infectious diseases by cell counts, reduced red blood cell counts, decreased enhancing the human immune system using OMT.11,12 In the Arnath index, and increased serum reticulocyte an essay discussing pneumonia, Still outlined his under- counts. The most robust changes from baseline were pinning philosophy that health is the result of a perfectly the immune function tests. Splenic pumping signifi- adjusted body and that disease is caused by the failure of cantly improved the mean phagocytic index, the op- the “osteopathic engineer” to obtain the normal position sonic index, the serum agglutinative power, and the of every bone, muscle, and nerve.13 The classic osteo- serum bacteriolytic power after treatment.19 pathic view is that OMT added to antimicrobial therapy In the 1920s, C.E. Miller, DO, developed the lym- will improve the chances of recovery from any infec- phatic pump technique for the express purpose of tion.14,15 Contemporary DOs still believe in OMT’s po- treating patients with all types of infectious diseases. tential role in managing infectious diseases, such as in His idea was that enhancing the lymphatic absorption the event of a serious influenza pandemic.16 This article of toxins (antigens) to the lymphoid tissues would en- reviews the evidence for using OMT as an adjunctive hance the production of antitoxins (antibodies) to fight treatment to antimicrobial therapy and its potential role infection.20 He originally attempted to do this by in antimicrobial stewardship. having the patient lie supine on the treatment table. Standing above the head with the 4 fingers of his hand in the axilla and the thumb just below the clavicle, Mechanistic Evidence Miller would gently pull or milk the lymphatic In 1912, C.A. Whiting, ScD, DO, studied the effects of glands.20 By 1927, his technique had evolved by liver and splenic stimulation on immune function using moving the operator’s hands medially to rest just under rhythmic compressions.17 A phagocytic index was ob- the clavicles over the terminal points of the thoracic The Journal of the American Osteopathic Association September 2016 | Vol 116 | No. 9 601 REVIEW Table. Contemporary Analysis of Whiting’s 1912 Measurements17 of the Phagocytic Index in 2 Patients Who Received Liver and Splenic Stimulation Hours After No. of Paired Mean Phagocytic Index Treatment Observations Baseline After Treatment 95% CI P Value 1 11 4.22 5.68 −2.108 to −0.815 .001 2 5 4.13 5.31 −1.710 to −0.650 .003 3 11 4.22 4.63 −0.986 to 0.168 .145 4 9 4.32 4.39 −0.727 to 0.576 .796 5 5 4.28 4.21 −0.280 to 0.404 .641 6 2 4.20 3.43 −5.769 to 7.319 .373 ducts. The operator would apply a rhythmic motion by populations, and pro-inflammatory cytokines. Castlio alternating pressure and release on the thorax, causing and Ferris-Swift found that splenic pumping had rela- the lymphatic ducts to empty when the thorax was de- tively little effect on the percentages of peripheral leu- pressed and to fill again when the pressure was re- kocyte cell types.18,19 In a study of 12 healthy medical leased.21 Miller coined the term thoracic pump to students (7 treatment, 5 control), pectoral traction with describe this technique.21 Other variations were splenic pumping caused a transient rise in basophils quickly developed and are collectively known today as relative to controls, but all other white blood cell types lymphatic pump techniques. in peripheral circulation were not affected.27 In another Lymphatic pumping improved the antibody response study of 20 relatively immobile nursing home residents, to pneumococcal polysaccharide vaccine in healthy male an OMT protocol had no effect on the percentages of medical students.22 Hepatitis B vaccine antibody titers white blood cell types present in peripheral circulation, rose faster in a group receiving lymphatic and splenic but 30 minutes after treatment the platelet counts were pump techniques.23 Dery et al24 were the first to use a rat significantly reduced in the OMT group relative to the model to show that rhythmic mechanical pressure in one