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Pyomyositis

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Written by: Dr Jason Chin; peer reviewer: Dr Jeremy Steinberg – created: 16 March 2022; last modified: 12 March 2023

Cor T2 MRI tropical pyomyositis.jpg
Coronal T2 weighted fat suppressed image showing a multiloculated fluid collection in the left gluteal musculature due to tropical pyomositis in a 12 year old boy.
Pyomyositis
Synonym Tropical pyomyositis
Epidemiology Typically young adults and children in tropical climates
Causes Staphylococcus aureus is the most common
Pathophysiology Disrupted muscle architecture during a period of bacteraemia
Risk Factors Trauma, IV drug use, chronic illness, immunosuppression
Clinical Features Three stages: invasive, purulent, and late stage.
Diagnosis Diagnosis is challenging and usually delayed.
Tests Inflammatory markers, CK. Ultrasound, CT, MRI
DDX Muscle contusion, fracture, transient synovitis, inflammatory arthritis, malignancy, thrombosis, osteomyelitis, septic arthritis.
Treatment Antibiotics, abscess drainage
Prognosis Good with treatment

Pyomyositis is a bacterial infection of the muscle, which can form abscesses and spread locally. It is relatively uncommon in temperate climates, often has an insidious onset, and can be difficult to diagnose[1][2][3]. It is even more challenging in the paediatric population where the history may not be clear, examination is inconsistent, and blood tests are non-specific[4].

It was initially described in 1885 as a disease predominating tropical areas (hence also known as tropical myositis or myositis tropicans)[5][6]. It differs from myositis in that it is always precipitated by bacteria and is confined to distinct areas in muscles[7].

Epidemiology

Pyomyositis can occur in any age group but typically affects young adults and children[3][8][9][10]. In a North American case review of 98 patients, 37% of patients were children less than 16 years old[4]. Another American review of 246 patients showed that 33% of patients were children[11]. There is also a male predominance, with male:female ratios observed from 1.5:1 to 3:1[4][7][8][11].

Pyomyositis is relatively uncommon in temperate climates[7]. In the tropics, the incidence of hospital admission for this varies from 1-4 percent[6]. There is little data to indicate a local incidence rate in New Zealand, however a 9 year study in Victoria, Australia estimated an incidence of 0.5 cases per 100,000 person-years[3].

Recently, the incidence of disease appears to be increasing, with a retrospective cohort study in Australia showing an increase from 2 cases to 8.7 cases per 10,000 ED admissions over a 10 year period[12]. The reasons for this are unclear.

Aetiology

Pyomyositis is often precipitated by trauma, with other predisposing factors including immunocompromise, chronic illness, IV drug use, and concurrent infection[3][5][6][7][9][13][14][15]. The role of trauma is supported by Miyake’s work in the early 1900’s where the experimental  conditions were identified that gave rise to abscess formation in staphylococcal bacteraemia[7]. When healthy rabbits were inoculated with IV boluses of staphylococcus, they occasionally developed small abscesses in the abdominal viscera, but never in skeletal muscle. When specific muscles were damaged by mechanical pinching or electricity, small abscesses developed within 2 days to 28 days following inoculation in some of the damaged muscles in nearly half of the rabbits, with no abscess formation in undamaged skeletal muscle. In addition, there have been a number of case reports of patients suffering from pyomyositis soon after exercise[16][17][18][19]. This suggests that the disrupted muscle architecture is at risk of promoting abscess formation during a period of bacteraemia.

This theory is also supported by a study from the British Army which showed that two-thirds of soldiers with pyomyositis had trauma at the affected site, and that the incidence of the disease increased as training intensity increased[20].

Up to 75% of reported cases are in immunocompromised patients, with the incidence of pyomyositis in those with human immunodeficiency virus (HIV) up to 31%[6].

In a review of 246 non-immunocompromised cases since 1981 in America, 48% of patients had at least one underlying disease[11]. The most common medical condition was diabetes mellitus, followed by malignancy, a rheumatologic disorder, liver cirrhosis, renal failure, then lung disease. This review also observed that the location of the infection was unifocal in 81% of cases. The thigh was the most common site of involvement, followed by the psoas muscle, then the upper extremities.

People with underlying medical conditions have a higher mortality, with mortality of up to 8% compared to 1% in those without underlying medical conditions in the literature review above[11]. A case series of over 200 cases in Nigeria showed overall mortality of 0.89%[1].

Microbiology

Staphylococcus aureus is the most common causative organism, with studies suggesting it causes up to 90 percent of cases in tropical areas, and up to 75 percent in temperate regions[7][10][15][21]. The next most common cause is Streptococcus pyogenes, accounting for 1-5 percent of cases[21]. Other organisms reported include non-group A streptococci, pneumococci, and gram-negative enteric bacilli such as Escherichia coli[3][6][9]. Gram-negative and anaerobic organisms are more common in immunocompromised patients[11].

Clinical features

Frontal view of patient with tropical pyomyositis in the left deltoid muscle
Lateral view of patient with tropical pyomyositis in the left deltoid muscle

Pyomyositis can be difficult to diagnose due to its relative rarity in temperate environments. In children, it is particularly challenging due to insidious, non-specific signs and symptoms, and a range of differential diagnoses including muscle contusion/sprain, fracture, transient synovitis, spondyloarthropathy, inflammatory arthritis, malignancy, thrombosis, and other infection such as osteomyelitis or septic arthritis. This often results in delayed diagnosis. Studies report a mean delay of 6-10 days from the onset of symptoms to diagnosis[2]. Non-accidental injury should always be considered.

Classical clinical features of pyomyositis include pain, stiffness, swelling, erythema, tenderness and fever. However, many of these are not present on presentation, and fever, if present at all, is cyclical in nature due to the bacteraemia[6]. The first symptom is usually pain, with fever not becoming common until later stages when a collection has formed[2][8]. As Chiedozi explains, the natural history of pyomyositis includes 3 stages: invasive, purulent and late stage[1]. The invasive stage begins with the insidious onset of dull, cramping pain in a large muscle, followed one week later by oedema, worsening pain and low grade fever. The examination reveals little in the way of inflammation with minimal swelling or fluctuance. A “wooden or hard rubber” feel on palpation may be appreciated. In Chiedozi’s series of 205 cases of pyomyositis in Nigeria, only 2 percent of the patients presented at this stage. Patients presenting between 10 and 21 days from the onset of symptoms are said to be in the purulent stage. They often display marked oedema and tenderness of the muscle, associated with fever and other signs of inflammation. More than 90 percent of Chiedozi’s case series presented in the purulent stage. The late stage is characterised by a systemically unwell patient, who may look toxic. Obvious fluctuance, tenderness, high fever, septicaemia and coma may occur.

A detailed history and examination should be taken, along with a full musculoskeletal examination, given that around 15-40% of cases will have multifocal infection[1][2][11]. A cardiorespiratory examination should not be omitted, as a number of cases of pyomyositis have been complicated by pyopericarditis and empyema[1].

Diagnosis

Transverse T2 MRI section through the hip region showing abscess collection in relation to the sciatic nerve in a patient with pyomyositis who presented with sciatica

Laboratory findings are non-specific, with 50-60% of patients displaying a leucocytosis[4]. Blood cultures are positive in 25-30% of patients in temperate regions, with organism identification usually from abscess culture[6][9].

Muscle enzymes such as creatine kinase are usually normal, or may be slightly elevated. This suggests that muscles are displaced rather than invaded by the infective process[2][8].

Acute phase reactants, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), are often raised, but again this is non-specific for pyomyositis[2][8][14][15][22].

While not specific to pyomyositis, a Finnish prospective trial of 265 children admitted to hospital, with bone or joint infections, attempted to identify the predictive value of certain laboratory tests in diagnosing bacteraemia[23]. It assessed the predictive value of white blood cell count, serum alkaline phosphatase, ESR and CRP. It found that none of the markers were able to stratify the risk of bacteraemia in children with an acute bone or joint infection. It did find that CRP was the only marker that was significantly higher in bacteraemic patients, and therefore could be used to predict bacteraemia, or used to distinguish between true positive cultures and contaminated cultures.

There are no studies that have assessed a clinical prediction algorithm for the diagnosis of pyomyositis.

Radiological imaging is important for diagnosing pyomyositis. Ultrasound is a relatively accessible, non-invasive, radiation sparing modality that can diagnose an abscess. The typical findings are of a bulky muscle with abnormal echotexture and a hypoechoic focal lesion, occasionally with internal debris and air bubbles[14].

When ultrasound is inconclusive, computed tomography (CT) or magnetic resonance imaging (MRI) is indicated. MRI is the investigation of choice as it provides the highest definition imaging, and when used with contrast, is the most sensitive and specific imaging for pyomyositis[6][11][14][24]. Pyomyositis is characterised on MRI by abnormal signal intensity within a skeletal muscle with irregular margins and an infiltrative appearance which shows a homogeneous and diffuse enhancement after gadolinium administration, without a defined mass effect[24].

When there is no focus on examination, but clinical suspicion is high, or if there are concerns of multifocal disease, gadolinium-based nuclear scintigraphy is effective at localising the infection[25].

Plain X-ray has little role in the diagnosis of pyomyositis. If performed, a soft tissue mass or wide fascial planes may be seen[7]. However, it may be useful if investigating for fracture, malignancy, or osteomyelitis.

Treatment

Stage 1 (invasive) pyomyositis, with the diffuse inflammatory process, may be treated with oral antibiotics alone. Most patients present in stage 2 (purulent) or stage 3 (late) disease, where abscess formation has occurred, and will require IV antibiotics plus drainage[1][6].

Initial treatment should begin with empiric antibiotics[1][11]. A broad spectrum antibiotic with Staphylococcus aureus and Streptococcal cover is appropriate. Locally, high dose IV flucloxacillin is the empiric antibiotic of choice. This will vary between geographic locations as it is dependent on the local microbe prevalence and susceptibilities. Patients with known or suspected methicillin-resistant Staphylococcus aureus (MRSA) must have vancomycin or clindamycin treatment considered. In immunocompromised patients, such as those with HIV, gram negative organism cover should be included[11].

The use of CT or ultrasound guided percutaneous catheter drainage has been shown to be effective and assists with both treatment and diagnosis[26]. It may spare the patient a general anaesthetic, allow a smaller incision, drain locations that would otherwise be a challenging surgical approach, and allow faster post-operative mobilisation[26].

In extensive infections, or if there is the possibility of concomitant osteomyelitis or septic arthritis, surgical exploration and drainage might be preferable.

Irrespective of the procedure performed, antibiotic therapy should not be delayed for the sake of obtaining a culture if the patient is toxic.

There is no consensus on duration of antibiotic therapy, as there is little data demonstrating recurrence or treatment failure[4][6]. In general, antibiotic treatment is recommended for 2-4 weeks, with IV therapy until clinical improvement is noted[1][4][7][11][27][28]. Some case series describe treatment up to 6 weeks[2].

Occasionally, penicillin-based antibiotics are ineffective when treating streptococcal pyomyositis[8]. This is postulated to be due to the “Eagle effect”[29]. Harry Eagle observed that penicillin had reduced antibacterial effect on older abscesses in mouse models and questioned the role of bacterial numbers. It has since been established that penicillin has a reduced efficacy when used in high bacterial loads[30]. It is thought that when treating established streptococcal infections, the organisms have reached a steady state of growth and the colony growth rate has slowed. Penicillin operates by inhibiting cell wall synthesis; therefore has reduced bactericidal activity when bacterial replication slows. In this situation, clindamycin, should be initiated[30]. Clindamycin interferes with protein synthesis at the ribosomal level and its efficacy is not affected by the growth phase of the bacterial colony.

Following successful treatment, there is very little residual deformity and minimal loss of function, even if there has been extensive muscle damage[1]. Physical therapy and rehabilitation might be necessary in severe cases, or in those who have required bed rest[6]. Studies have shown that a short term immobilisation (less than 14 days) results in a reduction of 5-10% in the muscle mass of vastus lateralis[31]. Even if there is no deformity or loss of function, patients may benefit from a rehabilitation program due to deconditioning associated with muscle disuse.

Summary

  • Pyomyositis is a bacterial infection of skeletal muscle which, if left untreated, forms abscesses and can lead to toxaemia. It was historically a disease of the tropics but is increasing in incidence in temperate climates.
  • The insidious nature of the disease can lead to delayed diagnosis, especially in children. Clinical features include pain and fever, with localised swelling and erythema. It most often affects the lower limb. A high level of suspicion is required, especially early in the course of the illness where fever may not be present.
  • Risk factors for pyomyositis include trauma, immunodeficiency, chronic illness, IV drug use and concurrent infection.
  • The most common causative organism is Staphylococcus aureus, followed by Streptococcus pyogenes.
  • MRI is the most useful diagnostic tool but is aided by blood work and bacterial identification from blood or aspirate cultures.
  • Treatment may be sufficient with antibiotic therapy alone. However, most cases present with some abscess formation (stage 2 or stage 3) and therefore also require drainage.
  • Initial antibiotic therapy should target Staphylococcus aureus and Streptococcus pyogenes. For immunocompromised patients, gram negative organism cover should be instituted. In those patients who are very unwell, or those who do not appear to be responding to a beta-lactam antibiotic, clindamycin should be considered due to the “Eagle effect”.
  • Treatment duration is not well established, but a period of 2-4 weeks is generally accepted.
  • Rehabilitation and physical therapy should be considered in those with deformity, loss of function, or where bed rest has been required.

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 Chiedozi, L.Chukwuma (1979-02). "Pyomyositis". The American Journal of Surgery (in English). 137 (2): 255–259. doi:10.1016/0002-9610(79)90158-2. Check date values in: |date= (help)
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 Mitsionis, Gregory I.; Manoudis, Gregory N.; Lykissas, Marios G.; Sionti, Ioanna; Motsis, Eustathios; Georgoulis, Anastasios D.; Berisa, Alexandros E. (2009-11). "Pyomyositis in children: early diagnosis and treatment". Journal of Pediatric Surgery (in English). 44 (11): 2173–2178. doi:10.1016/j.jpedsurg.2009.02.053. Check date values in: |date= (help)
  3. ↑ 3.0 3.1 3.2 3.3 3.4 Block, Andrew A; Marshall, Catherine; Ratcliffe, Alison; Athan, Eugene (2008-09). "Staphylococcal pyomyositis in a temperate region: epidemiology and modern management". Medical Journal of Australia. 189 (6): 323–325. doi:10.5694/j.1326-5377.2008.tb02050.x. ISSN 0025-729X. Check date values in: |date= (help)
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 Christin, L.; Sarosi, G. A. (1992-10-01). "Pyomyositis in North America: Case Reports and Review". Clinical Infectious Diseases. 15 (4): 668–677. doi:10.1093/clind/15.4.668. ISSN 1058-4838.
  5. ↑ 5.0 5.1 Burdette, Steven D.; Watkins, Richard R.; Wong, Ken K.; Mathew, Stephanie D.; Martin, Donald J.; Markert, Ronald J. (2012-05). "Staphylococcus aureus pyomyositis compared with non-Staphylococcus aureus pyomyositis". Journal of Infection. 64 (5): 507–512. doi:10.1016/j.jinf.2012.01.005. ISSN 0163-4453. Check date values in: |date= (help)
  6. ↑ 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 Woodward, Joseph F.; Park, James O.; Dellinger, E. Patchen (2012). "Pyomyositis (Pyomyositis Tropicans)". Elsevier: 292–294. Cite journal requires |journal= (help)
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 Grose, Charles (2009). "BACTERIAL MYOSITIS AND PYOMYOSITIS". Elsevier: 748–753. Cite journal requires |journal= (help)
  8. ↑ 8.0 8.1 8.2 8.3 8.4 8.5 GUBBAY, ANNA J.; ISAACS, DAVID (2000-10). "Pyomyositis in children". The Pediatric Infectious Disease Journal. 19 (10): 1009–1012. doi:10.1097/00006454-200010000-00015. ISSN 0891-3668. Check date values in: |date= (help)
  9. ↑ 9.0 9.1 9.2 9.3 Chiu, Nan Chang; Hsieh, Min Chun; Chi, Hsin; Huang, Fu Yuan (2009-12). "Clinical characteristics of pyomyositis in children: 20-year experience in a medical center in Taiwan". Journal of Microbiology, Immunology, and Infection = Wei Mian Yu Gan Ran Za Zhi. 42 (6): 494–499. ISSN 1995-9133. PMID 20422134. Check date values in: |date= (help)
  10. ↑ 10.0 10.1 Small, Lorne N.; Ross, John J. (2005-12). "Tropical and temperate pyomyositis". Infectious Disease Clinics of North America. 19 (4): 981–989, x–xi. doi:10.1016/j.idc.2005.08.003. ISSN 0891-5520. PMID 16297743. Check date values in: |date= (help)
  11. ↑ 11.0 11.1 11.2 11.3 11.4 11.5 11.6 11.7 11.8 11.9 Crum, Nancy F. (2004-09-15). "Bacterial pyomyositis in the United States". The American Journal of Medicine. 117 (6): 420–428. doi:10.1016/j.amjmed.2004.03.031. ISSN 0002-9343. PMID 15380499.
  12. ↑ Moriarty, Paul; Leung, Clare; Walsh, Mark; Nourse, Clare (2015-01). "Increasing Pyomyositis Presentations Among Children in Queensland, Australia". Pediatric Infectious Disease Journal. 34 (1): 1–4. doi:10.1097/inf.0000000000000470. ISSN 0891-3668. Check date values in: |date= (help)
  13. ↑ Ghazala, Christopher George; Fatone, Elena; Bentley, Ruth; Rajeev, Aysha (2016-09). "Primary Bacterial Gluteal Pyomyositis: A Rare Disease in Temperate Climates Presenting as Suspected Septic Arthritis of the Hip". The Journal of Emergency Medicine. 51 (3): 319–321. doi:10.1016/j.jemermed.2016.05.022. ISSN 0736-4679. Check date values in: |date= (help)
  14. ↑ 14.0 14.1 14.2 14.3 Taksande, Amar; Vilhekar, Krishna; Gupta, Sapna (2009-07). "Primary pyomyositis in a child". International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases. 13 (4): e149–151. doi:10.1016/j.ijid.2008.08.013. ISSN 1878-3511. PMID 19013093. Check date values in: |date= (help)
  15. ↑ 15.0 15.1 15.2 Gigante, C.; Borgo, A.; Cecchetto, G.; Turra, S. (2007-03). "Pyomyositis in children: report of three cases and review of the literature". Journal of Orthopaedics and Traumatology (in English). 8 (1): 29–32. doi:10.1007/s10195-007-0158-9. ISSN 1590-9921. PMC 4874979. Check date values in: |date= (help)CS1 maint: PMC format (link)
  16. ↑ Burkhart, Bradd G.; Hamson, Karl R. (2003-11). "Pyomyositis in a 69-year-old tennis player". American Journal of Orthopedics (Belle Mead, N.J.). 32 (11): 562–563. ISSN 1078-4519. PMID 14653488. Check date values in: |date= (help)
  17. ↑ Chusid, M. J.; Hill, W. C.; Bevan, J. A.; Sty, J. R. (1998-01). "Proteus pyomyositis of the piriformis muscle in a swimmer". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 26 (1): 194–195. doi:10.1086/517062. ISSN 1058-4838. PMID 9455539. Check date values in: |date= (help)
  18. ↑ Jayoussi, R; Bialik, V; Eyal, A; Shehadeh, N; Etzioni, A (1995-02). "Pyomyositis caused by vigorous exercise in a boy". Acta Paediatrica. 84 (2): 226–227. doi:10.1111/j.1651-2227.1995.tb13618.x. ISSN 0803-5253. Check date values in: |date= (help)
  19. ↑ Koutures, Chris G.; Savoia, Maria; Pedowitz, Robert A. (2000-10). "Staphylococcus Aureus Thigh Pyomyositis in a Collegiate Swimmer". Clinical Journal of Sport Medicine. 10 (4): 297–299. doi:10.1097/00042752-200010000-00013. ISSN 1050-642X. Check date values in: |date= (help)
  20. ↑ Ashken, M Handley; Cotton, R E (2005-12-06). "Tropical skeletal muscle abscesses (pyomyositis tropicans)". British Journal of Surgery (in English). 50 (226): 846–852. doi:10.1002/bjs.18005022621. ISSN 0007-1323.
  21. ↑ 21.0 21.1 Chauhan, S (2004-05-01). "Tropical pyomyositis (myositis tropicans): current perspective". Postgraduate Medical Journal (in English). 80 (943): 267–270. doi:10.1136/pgmj.2003.009274. ISSN 0032-5473. PMC 1743005. PMID 15138315.CS1 maint: PMC format (link)
  22. ↑ Ovadia, Dror; Ezra, Eli; Ben-Sira, Liat; Kessler, Ada; Bickels, Jacob; Keret, David; Yaniv, Moshe; Wientroub, Shlomo; Lokiec, Franklin (2007-03). "Primary pyomyositis in children: a retrospective analysis of 11 cases". Journal of Pediatric Orthopaedics B (in English). 16 (2): 153–159. doi:10.1097/BPB.0b013e3280140548. ISSN 1060-152X. Check date values in: |date= (help)
  23. ↑ Pääkkönen, Markus; Kallio, Markku JT; Kallio, Pentti E; Peltola, Heikki (2013-03). "C-reactive protein versus erythrocyte sedimentation rate, white blood cell count and alkaline phosphatase in diagnosing bacteraemia in bone and joint infections: CRP in bone and joint infections". Journal of Paediatrics and Child Health (in English). 49 (3): E189–E192. doi:10.1111/jpc.12122. Check date values in: |date= (help)
  24. ↑ 24.0 24.1 Soler, R (2000-07). "Magnetic resonance imaging of pyomyositis in 43 cases". European Journal of Radiology. 35 (1): 59–64. doi:10.1016/s0720-048x(99)00108-4. ISSN 0720-048X. Check date values in: |date= (help)
  25. ↑ Schiff, Robert G.; Silver, Lawrence (1990-08). "Tropical Pyomyositis: Demonstration of Extent and Distribution of Disease by Gallium Scintigraphy". Clinical Nuclear Medicine (in English). 15 (8): 542–544. doi:10.1097/00003072-199008000-00003. ISSN 0363-9762. Check date values in: |date= (help)
  26. ↑ 26.0 26.1 Geschwind, Jean-Francois H; Hamet, Marc (2001-02). "Use of Percutaneous Drain Insertion in the Management of Advanced Pyomyositis". Orthopedics. 24 (2): 187–189. doi:10.3928/0147-7447-20010201-24. ISSN 0147-7447. Check date values in: |date= (help)
  27. ↑ Melnyk, Megan; Casey, Rowan G.; Black, Peter; Koupparis, Anthony J. (2011-10-01). "Enhanced recovery after surgery (ERAS) protocols: Time to change practice?" (PDF). Canadian Urological Association Journal: 342–348. doi:10.5489/cuaj.11002. PMC 3202008. PMID 22031616.CS1 maint: PMC format (link)
  28. ↑ Stevens, Dennis L.; Bisno, Alan L.; Chambers, Henry F.; Dellinger, E. Patchen; Goldstein, Ellie J. C.; Gorbach, Sherwood L.; Hirschmann, Jan V.; Kaplan, Sheldon L.; Montoya, Jose G.; Wade, James C. (2014-07-15). "Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America". Clinical Infectious Diseases (in English). 59 (2): e10–e52. doi:10.1093/cid/ciu296. ISSN 1058-4838.
  29. ↑ Eagle, Harry; Musselman, A. D. (1948-07-01). "THE RATE OF BACTERICIDAL ACTION OF PENICILLIN IN VITRO AS A FUNCTION OF ITS CONCENTRATION, AND ITS PARADOXICALLY REDUCED ACTIVITY AT HIGH CONCENTRATIONS AGAINST CERTAIN ORGANISMS". Journal of Experimental Medicine (in English). 88 (1): 99–131. doi:10.1084/jem.88.1.99. ISSN 1540-9538. PMC 2135799. PMID 18871882.CS1 maint: PMC format (link)
  30. ↑ 30.0 30.1 Stevens, D. L.; Gibbons, A. E.; Bergstrom, R.; Winn, V. (1988-07-01). "The Eagle Effect Revisited: Efficacy of Clindamycin, Erythromycin, and Penicillin in the Treatment of Streptococcal Myositis". Journal of Infectious Diseases. 158 (1): 23–28. doi:10.1093/infdis/158.1.23. ISSN 0022-1899.
  31. ↑ Bodine, Sue C. (2013-10). "Disuse-induced muscle wasting". The International Journal of Biochemistry & Cell Biology (in English). 45 (10): 2200–2208. doi:10.1016/j.biocel.2013.06.011. PMC 3856924. PMID 23800384. Check date values in: |date= (help)CS1 maint: PMC format (link)

Literature Review

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