Cellulitis in Older Patients – a Prospective Cohort Study

CELLULITIS IN OLDER PATIENTS – A PROSPECTIVE COHORT STUDY

Older patient with cellulitis

Abstract

Aim: To examine differences in risk factors, clinical features and outcomes of cellulitis between those 75+ years and those < 75 years admitted to a metropolitan hospital.

Methods: A prospective study of patients with limb cellulitis requiring intravenous antibiotics conducted at Bankstown-Lidcombe Hospital, Australia from June 2014 to April 2015.

Results: Thirty one patients were 75+ years and 69 less than 75 years. A greater proportion of older patients resided in nursing home (25.8% vs 2.9% respectively, P=0.001) and mobilised with walking aid(s) (58.1% vs 11.6% respectively, P<0.001). Significantly more older patients had documented hypertension (45.2% vs 23.2% respectively P=0.035), atrial fibrillation (33.5% vs 5.8% respectively, P<0.001), dementia (22.6% vs 1.4% respectively, P=0.001) and malignancy (16.1% vs 1.4% respectively, P=0.010). The clinical presentation of cellulitis and cellulitis severity (Eron classification) did not significantly differ in both groups; however older patients were more likely to have dependent oedema (OR 4.0, CI 1.3-12.6, p=0.018) and less likely to be obese (OR 0.3, CI 0.1-0.8, p=0.012) or had a past history of cellulitis (OR 0.3, CI 0.1-1.0, P= 0.044) on presentation. Despite the age difference, there were no major differences in intravenous antibiotic choice, hospital length of stay, and hospital readmission rates in both groups. Older patients however, were more likely to experience complications such as falls and/ or decreased mobility (38.7% vs 15.9% respectively, P = 0.020) during the cellulitis episode.

Conclusion: Older patients with cellulitis performed just as well as younger patients despite having more medical comorbidities and worse physical function.

Keywords: Cellulitis, hospitalisation, older patients, prospective study,

Introduction

Cellulitis is a bacterial infection of the skin involving the dermis and subcutaneous fat. In Australia, cellulitis accounts for over 250,000 hospital bed days, or 10.5% of total bed days.¹ While most episodes of cellulitis can be managed as an outpatient, a significant proportion, particularly older people, require hospitalisation. Over a 12-month period from 2014-2015, the cellulitis hospitalisation rate was 1100 per 100,000 in the 80 plus age group as opposed to 237 episodes per 100,000 in the general population.¹

Cellulitis typically presents with pain, erythema, warmth and oedema. Systemic symptoms including fever and tachycardia may be presentalthough thought to be less frequent in older persons.^2-6 Known risk factors for cellulitis are venous oedema, lymphoedema, skin conditions, traumatic injury, leg ulcers, peripheral vascular disease, fungal infections, past history of cellulitis and obesity. ^7-10

Age alone does not alter treatment principles for bacterial cellulitis (including use of antibiotics); however age-related pharmacokinetics and pharmacodynamics, cognitive status and social circumstances¹¹ may impact on treatment decisions particularly need for hospitalisation.

Once hospitalised, age is an independent risk factor for increased length of stay for cellulitis with other factors being long duration of symptoms, tachycardia, hypotension, leukocytosis, hypoalbuminaemia, elevated serum creatinine, bacteraemia, obesity and diabetes mellitus. ^12-15

Age is significantly associated with increased mortality from cellulitis although it is unclear if this is due to illness severity or underlying comorbidity.¹⁶ Other factors associated with mortality are delayed administration of antibiotics, presence of multiple comorbidities, previous myocardial infarction, congestive heart failure, liver disease, hypoalbuminemia, renal insufficiency, morbid obesity, lower limb oedema, Pseudomonas aeruginosa infection, bacteraemia and septic shock.^14,17

Hospital readmission for cellulitis is also more common in older people¹⁸ particularly if there has been more than one prior episode of cellulitis^19.

Aims

In this prospective study, we aimed to examine differences in risk factors, clinical features, management, and outcomes of cellulitis between those 75 years or more and those less than 75 years admitted to a large metropolitan hospital.

Methods

The study was conducted at Bankstown-Lidcombe Hospital, New South Wales, Australia from June 2014 to April 2015. The study was approved by the South-Western Sydney Local Health District (SWSLHD) Ethics Committee.

Between June 2014 and April 2015, potential patients were identified through review of the Bansktown Hospital inpatient list three times a week by a study investigator. We included all identified patients aged 18 years or more with a diagnosis of cellulitis of the upper and/ or lower limb(s) and excluded patients with infected ulcers on presentation, pregnant patients and those with post-operative wound infections.

The patients were then stratified into an older group (aged 75 years or more) and a younger group (74 years or less) and were followed up during their admission and for a total of 28 days post completion of intravenous antibiotics.

Data collected included basic demographics, clinical characteristics, relevant investigations, treatment provided and clinical outcomes. The severity of cellulitis was rated using the Eron classification.²⁰

Data were analysed with SPSS Version 24 and R version 3.3.1. Chi-square test was used to compare proportions. Student’s T-test was used to compare differences in means for normally distributed variables. For non-normally distributed continuous variables, non-parametric test was used to assess differences in the ranked median scores. Logistic regression was used to assess statistically significant risk factors for cellulitis in the older and younger age groups. Statistically significant results were set at an alpha level of 0.05.

Results

One hundred and thirteen patients were identified during the study period and 100 patients (88.5%) consented to participate. Thirty-one (31.0%) patients were aged 75 years and older and 69 (69.0%) patients were 74 years or less.

The mean age was 84.4±5.8 years in the older group and 53.4±14.2 years in the younger group. The older patients had lower BMI than their younger counterparts [28.3 (±8.0) vs 36.0 (±12.3) respectively, P<0.001]. A higher proportion resided in residential aged care facilities (25.8% vs 2.9% respectively, P=0.001); and mobilised with walking aid(s) (58.1% vs 11.6% respectively, P<0.001). (Table 1)

A significantly higher proportion of older patients had documented hypertension (45.2% vs 23.2% respectively P=0.035), atrial fibrillation (33.5% vs 5.8% respectively, P<0.001), dementia (22.6% vs 1.4% respectively, P=0.001) and malignancy (16.1% vs 1.4% respectively, P=0.010). (Table 1)

In terms of cellulitis risk factors, after controlling for potential confounders, older patients were more likely to have dependent odema (OR 4.0 CI 1.3-12.6, p=0.018); but less likely to be obese (OR 0.3, CI 0.1-1.0, P=0.012) or had a prior history of cellulitis (OR 0.3, CI 0.1-1.0, P= 0.044) than younger patients. The risk of peripheral vascular disease, tinea pedis and cutaneous dermatitis were similar in both groups.

Cellulitis presenting features such as pain, fever, chills and vital signs (temperature, heart rate and blood pressure) did not significantly differ between the two groups. The severity of cellulitis, as defined by the Eron classification also did not differ between groups with the majority of patients having Eron Classes I and II. (Table 1)

Initial laboratory results revealed that older patients had lower hemoglobin [122.1 (±16.4) vs 135.0 (±19.4), P=0.002] and albumin [38.0 (±47) vs 41.4 (±4.1), P<0.001] and higher urea level [7.9 (5.8-12.4) vs 5.8 (4.8-8.4), P=0.011] compared to their younger counterparts. CRP white cell count (WCC) and positive rate of blood culture did not differ between the two groups. (Table 2)

Older inpatients presenting with cellulitis were less likely to be referred to hospital in the home (HITH) antibiotic programs for completion of the course of intravenous antibiotics 32.3% vs 59.4% respectively, P=0.012) compared to younger patients. The antibiotic choices did not differ between the two populations, these included cephazolin, flucloxacillin or tazobactam-piperacillin.

Older patients with cellulitis were more likely to experience falls or decreased mobility (38.7% vs 15.9% respectively, P = 0.020) compared to the younger group. (Table 2). Despite this, they had similar LOS to their younger counterparts [10 (7-15) vs 8 (6-13) respectively, P=0.403]. There was one death in each group and the rates of ICU admission, surgical intervention and 28-day readmission were similar in the two groups.

Discussion

In this study, we found that older people, despite being frailer than their younger counterparts, had similar treatment outcomes after presenting to hospital with mild to moderate limb cellulitis.

In our study, most of the potential risk factors for cellulitis were similar in the older and younger age groups; however, older patients were more likely to have dependent oedema and impaired mobility, and less likely to be obese. Other conditions noted to be more common in the older group were congestive cardiac failure, atrial fibrillation, dementia and malignancy. We believe this finding reflected the higher prevalence of these conditions in the older population rather than an association with cellulitis.

Over 25% of older patients with cellulitis lived in residential aged care facilities. This finding raised the opportunity for the provision of ambulatory care antibiotic programs in aged care homes potentially avoiding the need for hospitalisation for residents with cellulitis.

There were no significant differences in the clinical presentation of cellulitis between the two age groups (i.e., duration of cellulitis symptoms, heart rate, blood pressure, temperature, white cell count, CRP and Eron severity classification). Atypical and blunted physiological response to infection with age has been documented in the literature. In severe sepsis, a reduced physiological response can lead to rapid progression of sepsis .^{2,3, 21} Our results did not support a blunted response to infection in older patients with cellulitis; we, however, did not have any patients with severe sepsis to examine the inflammatory response in more detail.

In our study, older patients experienced more falls and impaired mobility during the admission for cellulitis compared to younger patients. While these factors might have made their hospital discharge planning more complex, they did not translate into an increased hospital length of stay. Previously described risk factors affecting LOS in cellulitis (comprising of age, hypoalbuminaemia, bacteraemia, obesity, diabetes mellitus, tachycardia, hypotension, leukocytosis, and elevated serum creatinine), ^{7,12,13,14,15} tended to be skewed towards age and hypoalbuminaemia for the older group and obesity for the younger group in our study.

There were no statistically significant differences between the two groups in terms of mortality, ICU admission, and surgical intervention for cellulitis complications. The majority of patients in both groups had Eron Class I or II cellulitis and did not sustain physiological decompensations; however, in more severe cases of cellulitis, one would expect ageing physiology to sustain more physiological decompensations which may then influence the above parameters.

A lower proportion of older inpatients discharged to HITH programs might have been attributable to their medical comorbidities and functional criteria not meeting HITH requirements. As such, additional health resources may allow HITH programs to manage these complex patients but this would require further study.

Unlike previous published literature, ¹⁸we did not find a significant difference in the 28-day readmission rate between the two age cohorts in our study. As the readmission rate was less than 5%, a study with greater number of patients would have more power to detect small differences in readmission rates.

One of the limitations of this study is the small sample size due to a short recruitment period; further study with a larger sample size would assist in validation of our findings. We decided to focus on inpatient cellulitis treatment; however a cellulitis management journey from hospital to community settings would have provided with a more complete picture.

As the number of older patients presenting with cellulitis increases as the population ages, it is important to note that for mild to moderate cellulitis, older patients perform just as well as younger patients with standard cellulitis treatments on clinical and care indicators.

No potential conflicts of interests were disclosed by all the authors.

References

1. National health performance authority analysis of admitted patients care national minimal data set 2013-2014 and Australian Bureau of statistics estimated resident population 30 June 2013

2. Anderson DJ, Kaye KS. Skin and soft tissue infections in older adults.Clin Geriatr Med. 2007; 23(3): 595–613.

3. Laube S. Skin infections and ageing. Ageing Res Rev. 2004;3(1): 69–89.

4. Weng QY, Raff AB, Cohen JM, Gunasekera N, Okhovat JP, Vedak P, et al. Costs and consequences associated with misdiagnosed lower extremity cellulitis. JAMA Dermatol. 2017;153(2): 141–146.

5. Gunderson CG, Martinello RA. A systematic review of bacteremias in cellulitis and erysipelas.J Infect. 2012;64(2): 148–155. doi: 10.1016/j.jinf.2011.11.004.

6. Esposito S, Noviello S, Leone S Epidemiology and microbiology of skin and soft tissue infections Current Opinion in Infectious Diseases 2016; 29(2):109–115.

7. Dupuy A, Benchikhi H, Roujeau JC, Bernard P, Vaillant L, Chosidow O, et al. Risk factors for erysipelas of the leg (cellulitis): case-control study. BMJ. 1999;318(7198): 1591–1594.

8. Björnsdóttir S, Gottfredsson M, Thórisdóttir AS, Gunnarsson GB, Ríkardsdóttir H, Hilmarsdóttir I. Risk factors for acute cellulitis of the lower limb: a prospective case–control study. Clin Infect Dis. 2005;41(10): 1416–1422.

9. Karppelin M, Siljander T, Vuopio-Varkila J, Kere J, Huhtala H, Vuento R, et al. Factors predisposing to acute and recurrent bacterial non-necrotizing cellulitis in hospitalized patients: a prospective case–control study. Clin Microbiol Infect. 2010;16(6): 729–734.

10. Halpern J, Holder R, Langford NJ. Ethnicity and other risk factors for acute lower limb cellulitis: a U.K.-based prospective case–control study. Br J Dermatol. 2008;158(6): 1288–1292.

11. Kish TD, Chang MH, Fung HB. Treatment of skin and soft tissue infections in the elderly: a review. Am J Geriatr Pharmacother. 2010;8(6):485–513.

12. Garg A, Lavian J, Lin G, Sison C, Oppenheim M, Koo B. Clinical characteristics associated with days to discharge among patients admitted with a primary diagnosis of lower limb cellulitis. J Am Acad Dermatol. 2017;76(4): 626–631.

13. Morpeth SC, Chambers ST, Gallagher K, Frampton C, Pithie AD. Lower limb cellulitis: features associated with length of hospital stay. J Infect. 2006;52(1): 23–29.

14. Figtree M, Konecny P, Jennings Z, Goh C, Krilis SA, Miyakis S. Risk stratification and outcome of cellulitis admitted to hospital. J Infect. 2010;60(6):431–439.

15. Theofiles M, Maxson J, Herges L, Marcelin A, Angstman KB.Cellulitis in obesity: adverse outcomes affected by increases in body mass index. J Prim Care Community Health. 2015;6(4): 233–238.

16. Tan R, Newberry DJ, Arts GJ, Onwuamaegbu ME. The design, characteristics and predictors of mortality in the North of England Cellulitis Treatment Assessment (NECTA). Int J Clin Pract. 2007;61(11): 1889–1893.

17. Carratalà J, Rosón B, Fernández-Sabé N, Shaw E, del Rio O, Rivera A, et al. Factors associated with complications and mortality in adult patients hospitalized for infectious cellulitis. Eur J Clin Microbiol Infect Dis. 2003;22(3): 151–157.

18. Garg A, Lavian J, Lin G, Sison C, Oppenheim M, Koo B. Clinical factors associated with readmission among patients with lower limb cellulitis. Dermatology. 2017;233(1): 58–63.

19. Karppelin M, Siljander T, Aittoniemi J, Hurme M, Huttunen R, Huhtala H, et al. Predictors of recurrent cellulitis in five years. Clinical risk factors and the role of PTX3 and CRP. J Infect. 2015;70(5): 467–473.

20. Eron, L. J. 2000. Infections of skin and soft tissues: outcome of a classification scheme. Clinical Infectious Diseases. 31, 287 (A432).

21. Norman DC, Grahn D, Yoshikawa TT (1985) Fever and aging. J Am Geriatr Soc 33: 859.

Table 1. Patient Characteristics

† Logistic regression – Chi-square = 17.868, p=0.007, df=6, Nagelkerke’s R2 0.230; BMI body mass index; IHD ischaemic heart disease; AF atrial fribrillation; CCF congestive cardiac failure; DVT deep vein thrombosis; PE pulmonary embolism; CRP C reactive protein.

HiTH hospital in the home; DVT deep vein thrombosis; PE pulmonary embolism