Erysipelas and cellulitis: important "hot topics"

Two recent studies of practical relevance deal with questions about the purpose of blood cultures and when is the right time to switch from intravenous to oral antibiotics. It has been shown that around 95% of cases of cellulitis or erysipelas respond to treatment with beta-lactam antibiotics (e.g. penicillin), even without evidence of the pathogen. Alternatives are available for penicillin allergy sufferers.

Cellulitis and erysipelas are classified as bacterial skin and soft tissue infections (SSTI). Prof. Dr. med. Parham Sendi, Institute for Infectious Diseases, University of Bern, presented current study data and expert recommendations. In 80-90% of cases of cellulitis and erysipelas, the pathogens are beta-hemolytic streptococci or Staphylococcus aureus (S. aureus), with distribution patterns varying depending on the study and geographical region (Table 1). The speaker answered the question frequently asked in practice as to whether a blood culture is necessary for skin and soft tissue infections as follows [1]: In the case of cellulitis and erysipelas, the majority of cases still do not require a blood culture or are not recommended by guidelines, as the rate of positive findings is relatively low (4-13%) and there are hardly any treatment-relevant implications as a result [2,3].

Blood culture: relevance of comorbidities

However, there are individual cases of patients with certain diseases where it is important not to miss S. aureus colonization, Prof. Sendi admitted [1]. This applies, for example, to patients with comorbid conditions such as diabetes mellitus, obesity or kidney disease requiring dialysis. In a retrospective study by van Daalen et al. The study included 334 patients with cellulitis and wound infections recruited between 2011 and 2015 [4]. The acute clinical condition of the patients was assessed using the Modified Early Warning Score (MEWS; severe: MEWS ≥2) and the comorbidities using the Charlson Comorbidity Index (CCI; severe: CCI ≥2). Blood cultures were performed in 53% and 61% of patients with severe and without severe comorbidity, respectively, and were positive in 25% and 10%, respectively (odds ratio 3.1; 1.2-7.5; p=0.02). S. aureus was identified as the pathogen in 3 out of 5 patients with a positive blood culture. As a result, the positivity rates of blood cultures in hospitalized patients with skin infections were higher than the rates specified in the guidelines of the Infectious Diseases Society of America, particularly in the presence of severe comorbidities [4]. Remarkably, gram-negative bacteria were detected in 4 out of 8 patients diagnosed with erysipelas. The previously prevailing doctrine that erysipelas is mainly caused by colonization with streptococci (=gram-positive) has now been put into perspective, explained Prof. Sendi [1].

Use penicillin or broad-spectrum antibiotics

In a prospective study of 179 cellulitis patients, 73% of whom were due to beta-hemolytic streptococci (BHS), 97% of BHS patients responded to treatment with beta-lactam antibiotics, compared with 95.8% of patients without BHS [5]. Clindamycin is recommended as an alternative for SSTI patients with a penicillin allergy. Doxycycline should not be given because the resistance data for streptococci are poor, Prof. Sendi reported. For the local context, he recommends consulting the constantly updated ANRESIS website of the federal government once a year in order to obtain regional information on pathogens and resistance data.

On the question of which patients should be started on intravenous (IV) therapy, the speaker suggested the following rule of thumb [1]: If a patient with a skin or soft tissue infection S. aureus is suspected as the pathogen, intravenous therapy should be initiated so that the patient receives a sufficient dose within a reasonable period of time.

Criteria-based switch from i.v. to per os

What is the best time to switch from intravenous treatment to oral therapy? Dellsperger et al. In the canton of Bern, a non-randomized study was conducted in which 128 patients who had been hospitalized with an SSTI between July 2019 and May 2021 were included [6]. Certain criteria were defined for allocation to the intervention vs. control arm. These included clinical response to the therapy in terms of

an improved general condition and a regression of symptoms. 75.8% of patients met the criteria for switching from i.v. to per os and were assigned to the intervention group. All showed signs of clinical improvement (i.e. absence of fever or pain relief) within 48 hours of IV treatment, regardless of erythema findings or biochemical response. The median total duration of antibiotic treatment was 11 days in the intervention group and 15 days in the non-intervention group (p<0.001). The median length of hospitalization was 5 days in the intervention group and 8 days in the non-intervention group (p<0.001). After a median follow-up period of 37 days, there were 5 (5.2%) failures in the intervention group and 1 (3.2%) in the non-intervention group. In summary, the proposed decision algorithm of switching from intravenous to oral antibiotic treatment within 48 hours was successful in 95% of cases in this pilot study.

What are the risk factors for recurrent cellulitis?

As a rule, cellulitis occurs unilaterally and is most frequently localized on the lower extremity. Around 35-47% of patients who present to hospital with cellulitis have already had a previous episode [7]. Reducing the duration and severity of cellulitis is likely to reduce the risk of recurrence, with many of the risk factors for recurrent cellulitis being directly or indirectly related to chronic edema [8]. In a meta-analysis based on six case-control studies, chronic lymphedema was identified as an independent risk factor for cellulitis (odds ratio of 6.8) [9]. The cause of lymphoedema is a deficiency, reflux or obstruction of the lymph vessels, which leads to a dysfunction of the lymphatic system. This results in impaired resorption of proteins from the interstitium and interstitial edema due to the osmotic gradient. It is typical of protein-rich edema that tissue remodeling processes occur over the years, which lead to additional fibrosis and sclerosis. In such lymph congestion areas, the body’s defense mechanisms are usually weakened, which increases susceptibility to infection. It is estimated that more than a third of patients with chronic lymphoedema develop recurrent cellulitis, with the risk increasing with the severity of the oedema [7,12]. But obesity is also cited as a risk factor. In the meta-analysis by Quirke et al. a BMI>30 was associated with an odds ratio of 2.4 for a (new) episode of cellulitis [9]. By treating the risk factors – in addition to those already mentioned, these include ulcers and intertrigo of the spaces between the toes – a recurrence of cellulitis can also be counteracted.

Congress: Swiss Derma Day and STI reviews and updates

Literature:

“Erysipelas and cellulitis: treatment and procedure”, Prof. Dr. med. Parham Sendi, Swiss Derma Day and STI reviews and updates, 11.01.2024.
Stevens DL, et al; Infectious Diseases Society of America. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis 2014 Jul 15; 59(2):e10-52
Paolo WF, et al: Blood culture results do not affect treatment in complicated cellulitis. J Emerg Med 2013; 45(2): 163-167.
van Daalen FV, et al: Clinical condition and comorbidity as determinants for blood culture positivity in patients with skin and soft-tissue infections. Eur J Clin Microbiol Infect Dis 2017; 36(10): 1853-1858.
Jeng A, et al: The role of beta-hemolytic streptococci in causing diffuse, nonculturable cellulitis: a prospective investigation. Medicine (Baltimore) 2010; 89(4): 217-226.
Dellsperger S, et al: Early Switch From Intravenous to Oral Antibiotics in Skin and Soft Tissue Infections: An Algorithm-Based Prospective Multicenter Pilot Trial. Open Forum Infect Dis. 2022 Apr 12; 9(7): ofac197.
Ong BS, Dotel R, Ngian VJJ: Recurrent Cellulitis: Who is at Risk and How Effective is Antibiotic Prophylaxis? Int J Gen Med 2022; 15: 6561-6572.
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Quirke M, et al: Risk factors for nonpurulent leg cellulitis: a systematic review and meta-analysis. Br J Dermatol 2017; 177(2): 382-394.
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Burian EA, et al: Cellulitis in chronic oedema of the lower leg: an international cross-sectional study. Br J Dermatol 2021; 185(1): 110-118.