Candida tropicalis cellulitis in a patient with cirrhosis, well-controlled HIV and diabetes

Abstract

We present the case of a patient with multiple comorbidities, including cirrhosis, poorly controlled diabetes mellitus and HIV infection, who was diagnosed with skin and soft-tissue infection of right lower limb. Outcome was poor after prescribing standard antibiotic therapy, and we finally obtained isolation of Candida tropicalis in cultures of infected tissue. The patient’s condition improved after antifungal treatment was started, and he could be discharged with oral therapy. Here, we report the literature’s first case of cellulitis provoked by C. tropicalis in a patient with cirrhosis.

Background

To the best of our knowledge, there are only two cases reported of cellulitis due to Candida tropicalis, but in the context of lymphomas.

Case presentation

We report here the case of a 54-year-old man with history of diabetes mellitus with microvascular (neuropathy and microalbuminuria) and macrovascular complications (acute myocardial infarction 4 years earlier in a hypertensive emergency), and last HbA1c% (glycosylated hemoglobin) 1 month earlier of 6.7%. In addition, he suffers from liver cirrhosis due to NASH (non-alcoholic steatohepatitis) disease and HCV (hepatitis C virus) infection, treated in 2005 with sustained virological response, and functional grade Child-Pugh-Turcotte B7 with pancytopenia and no decompensations. And finally, he was diagnosed with HIV nfection stage III in 1995, parenteral route of transmission (intravenous drug user) and last lab control 2 months before admission (CD4 T cell count 69 cells/µL (15.6%), CD4/CD8 ratio 0.25 and suppressed viral load (<20 copies/mL)). Antiretroviral treatment was based in emtricitabine/tenofovir alafenamide/bictegravir.

He consulted our emergency department for cellulitis in the lower right limb during last 5 days. His primary care physician had recommended empirical treatment with amoxicillin/clavulanic acid 875/125 mg every 8 hours but he experienced worsening of local symptoms and high fever. Physical examination showed good general condition with no sepsis signs. Right lower limb cellulitis consisted of expanding erythema, warmth, tenderness and swelling between knee and ankle. No bullae, blisters or crackle were identified (figure 1).

Figure 1.

At the admission.

Laboratory tests showed normal renal function, pancytopenia secondary to hypersplenism with no changes respect to baseline levels, similar liver function, normal creatine-phosphokinase and lactate dehydrogenase (LDH), with elevation of C-reactive protein (CRP) around 70 mg/L (upper limit 10 mg/L) and mild coagulopathy. X-ray was performed showing no evidence of osteomyelitis.

We obtained samples for microbiological culture, and a rapid test for Streptococcus pyogenes (negative). We started intravenous treatment with ceftriaxone 2 g every 24 hours and clindamycin 600 mg every 8 hours. In the first days of admission, patient’s clinical course worsened (figure 2) so we changed antibiotic coverage to meropenem 1 g every 8 hours and linezolid 600 mg orally every 12 hours. Ultrasound of the lower limb ruled out deep vein thrombosis, abscess, fasciitis and myositis. Neither MRI nor CT could be performed because the patient’s weight exceeded limits of the devices (body mass index 50.9 kg/m²).

Figure 2.

Before starting antifungal treatment.

Finally, C. tropicalis was isolated in the cultures (in three consecutive samples) so we started treatment with caspofungin. We could de-escalate to fluconazole 400 mg two times per day 48 hours later, according to azole minimum inhibitory concentration (MIC). Infection evolved appropriately and he was discharged to complete outpatient treatment for 6 weeks.

Outcome and follow-up

We reassessed the patient 2 weeks after hospital discharge and could appreciate excellent progress of infection but he needed another fluconazole course 1 month later because of mild worsening. Low-dose fluconazole suppressive treatment has been prescribed.

Discussion

The skin is one of the largest organs of the human body that acts as a physical protective barrier against external pathogens, among other functions.^{1 2} It is colonised by a heterogeneous group of micro-organisms, mainly bacteria, fungi and parasites, which usually coexist without causing disease in humans.² In certain situations, due to alterations in the physical barrier itself or due to personal conditions, these microorganisms can cause localised or disseminated infections.^{2 3}

Cellulitis is a type of infection that mainly affects the dermis and subcutaneous tissue. Clinically, it presents as a poorly defined, erythematous, raised, hot and painful lesion that may associate blisters or small petechial lesions and in some cases it may develop into ulcers.^4–6 In addition, systemic symptoms such as fever and other symptoms related to the systemic inflammatory response may appear.^4–6

Usually, a history predisposes to infection, although it is not always found.⁴ The main risk factors associated with Cellulitis are^4–8: any mechanism, traumatic or not, that conditions the breakdown of the skin barrier that facilitates the entry of microorganisms: wounds, bites, pressure ulcers, injection drug use, skin inflammation (radiation therapy), skin oedema (venous or heart failure or alterations in lymphatic drainage) or previous skin infections (chickenpox or zoster); the use of recent antibiotic therapy has also been described as a risk factor for the development of skin and soft-tissue infections; immunosuppression caused by diabetes, liver cirrhosis, haematological diseases, transplants, chemotherapy, chronic corticosteroids or HIV infection, also favour this type of infection.

In our case, the patient presented several of conditions that favoured the development of cellulitis, including diabetes mellitus with microvascular and macrovascular involvement, cirrhosis with pancytopenia secondary to hypersplenism and chronic HIV infection with advanced immunosuppression.

As we have already commented previously, the most common pathogens that cause cellulitis are Staphylococcus aureus and streptococci, however, in immunosuppressed patients due to any cause, other less common micro-organisms appear, among others, fungi. Within the fungal aetiology, Candida is the most frequently isolated micro-organism in immunosuppressed patients; specifically Candida albicans is the one with the highest prevalence in these patients. Nonetheless, in the last few years, the frequency of the non albicans-Candida group has increased, among them, the most common is C. tropicalis, which is becoming increasingly important in immunosuppressed patients in addition to its mortality, also due to the high rate of resistance to azoles.^{3 9 10}

Generally, candida skin lesions are the consequence of haematogenous dissemination secondary to disseminated candidaemia, although occasionally and less frequently, they can also produce primary lesions, as in this case, mainly in immunosuppressed patients.^{9 11 12}

In HIV patients, skin infections such as folliculitis, balanitis or cellulitis due to the typical bacteria of these infections are frequent, although in advanced immunosuppression stages, as in our case, other aetiologies such as Candida can also appear.²

In the case of cirrhotic patients, they are more susceptible to bacterial and fungal infections, mainly secondary to candida, due to the state of immunosuppression that is generated in advanced stages of the disease, therefore, it is essential to take into account the fungal aetiology in this type of patients.¹³

We also know that patients with diabetes due to involvement of the microvasculature, in addition to the alteration of the immune system, have a higher risk of developing skin fungal infections.¹⁴

Fungal infections are widely described in haematological patients, including those with haematological malignancies, prolonged neutropenia and haematopoietic stem cell transplantation.^{15 16} In our case, the patient presented pancytopenia secondary to hypersplenism, which, although mild, could also favour, along with the other conditions, the appearance of a fungal infection of the skin and soft-tissue.

In any patient with an active infection, but more specifically in immunosuppressed patients, an infection by multiresistant micro-organisms or fungal aetiology should be suspected in patients with severe clinical manifestations or those who do not progress favourably despite adequate antibiotic treatment that covers the most frequent causes.^{17 18} In our case, the patient presented an unfavourable evolution despite the change of antibiotic treatment to cover resistant micro-organisms and the patient did not present clinical improvement until the beginning of antifungal coverage.

Learning points.

• Any type of immunosuppression is a risk factor for developing infections caused by micro-organisms that do not usually affect healthy population, such as fungal infections.

• If a patient has a poor outcome, we must think about atypical pathogens or resistances to standard therapy.

• We must remember that unusual species have emerged in recent years, such as non-Candida albicans species, which present diagnostic and therapeutic challenges, mainly due to the risk of resistance to standard treatments.

Ethics statements

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