Conservative approach for intra-amniotic Candida albicans colonisation. Case report and review of current evidence

Obstetric management

In this case, we highlight the complexity of diagnosing and differentiating between MIAC and IAI caused by C. albicans. MIAC is defined as intra-amniotic colonisation without an associated inflammatory response or other clinical findings [7]. In contrast, IAI typically presents as a subclinical infection but may also manifest as miscarriage, cervical insufficiency, PPROM, or TPL. However, infection has also been reported as occurring secondary to PPROM or cervical insufficiency. In such scenarios, prolonged exposure of the membranes to vaginal flora may facilitate microbial invasion [3], 5]. In our case, both hypotheses regarding fungal invasion were considered: the presence of vaginal infection at the time of cerclage could have facilitated C. albicans invasion into the amniotic cavity, leading to PPROM, or the amniotic cavity could have been invaded following PPROM. Given the rupture of membranes without evidence of a significant inflammatory response, our initial diagnostic assessment was more consistent with intra-amniotic colonisation rather than IAI.

In addition, the diagnosis of IAI is further complicated because laboratory tests typically show no obvious signs of infection, and ultrasound findings are often limited to a single indicator: intra-amniotic sludge, which has been identified as a factor in recognising patients at risk of IAI [3], 5]. Consequently, the usual clinical and laboratory criteria for a presumptive diagnosis of IAI are often not met, and the condition is diagnosed only after the analysis of amniotic fluid. Definitive confirmation is established through characteristic histopathological findings on examination of the placenta and umbilical cord [2], 8].

Regarding the treatment of VV, recent studies indicate that vaginal colonisation by Candida spp. in pregnancy, whether asymptomatic or symptomatic, does not increase the risk of preterm birth or negatively affect pregnancy outcomes. However, in cases where VV due to Candida spp. is diagnosed, the predominant recommendation is the use of vaginal clotrimazole, owing to its potential protective effect in preventing preterm birth, which is attributed to its anti-inflammatory properties rather than its antifungal action [1], 9].

Systemic intravenous strategies or intra-amniotic injections have been proposed for the management of fungal intra-amniotic invasion. These interventions prolong gestation from 0 days to 8 weeks; however, it is important to consider that neonatal survival is less than 50 % [9]. Currently, intra-amniotic fluconazole is the most widely used antifungal agent despite its associated risks and limitations [10], [11], [12]. This drug crosses the placental membrane and, although there are reports of possible teratogenic effects, the most recent meta-analyses have not demonstrated a direct association with congenital anomalies, except for a potential risk of cardiac malformations following oral administration during the first trimester [13], [14], [15]. In addition, it has shown reduced activity against Candida glabrata, the second most prevalent species. Following intra-amniotic administration, foetal serum concentrations achieved are higher than maternal levels [5], 10]. Other studies have proposed amphotericin B as the preferred antifungal agent for the management of intra-amniotic colonisation in pregnant women, owing to its ability to cross the placenta without reported adverse effects on the foetus, as well as its greater efficacy against C. glabrata. The use of ketoconazole and micafungin has also been documented, although their efficacy and potential adverse effects remain uncertain [3], 5]. In our case, we opted for intravenous therapy rather than intra-amniotic instillation, based on evidence suggesting that maternal intravenous treatment achieves therapeutic levels in foetal circulation [10], rendering intra-amniotic administration unnecessary and potentially increasing the risk of toxicity and procedure-related complications [5], 10]. Therefore, our initial preference was to use a broader-spectrum antifungal agent with a lower resistance rate and a more favourable teratogenicity profile, which led us to initially opt for amphotericin B. However, following an anaphylactic reaction to this agent, and considering the gestational age, we regarded fluconazole as a safe and appropriate alternative therapeutic option.

Concerning MIAC, there is currently no established guidance on optimal management or timing of delivery [7]. For this reason, our decisions were guided by the available literature on Candida IAI. Current data indicate that once IAI is established, it typically progresses to spontaneous labour. In cases where this does not occur, antifungal therapy is initiated, antenatal corticosteroids are administered, and delivery is planned beyond 34 weeks’ GA. According to the limited evidence available on Candida IAI, in asymptomatic pregnant women under 34 weeks GA who are clinically and biochemically stable, the timing of delivery should be individualised [8], 16], 17]. Based on this, we opted for a conservative management approach. After two weeks of fluconazole treatment, C. albicans remained positive in the third AC. Consequently, following a comprehensive multidisciplinary risk–benefit assessment, the pregnancy was electively delivered by caesarean section.

Neonatal management

The most typical form of candidal placental infection is funisitis. This case presented these characteristic lesions along the entire umbilical cord.

Congenital candidiasis in neonates may present with a broad clinical spectrum, ranging from isolated cutaneous involvement to disseminated systemic disease. Due to the rarity of reported cases and the limited body of available literature, establishing standardised management guidelines remains challenging. The primary risk for a foetus with intra-amniotic candidiasis is the development of congenital cutaneous candidiasis (CCC). CCC usually follows a benign course; however, in low birthweight preterm infants (<1,000 g), it presents a higher risk of progression to a systemic form, for which treatment with systemic antifungal agents is recommended [18], [19], [20].

The systemic form may or may not be accompanied by cutaneous manifestations and is typically followed by respiratory distress, sepsis, or meningitis. This form is particularly severe and affects preterm infants in greater proportion due to their immunosuppression and the non-integrity of mucocutaneous barriers. A mortality rate of 39–94 % has been reported. Early diagnosis and prompt treatment with antifungal agents are crucial [21].

First-line treatment is based on amphotericin B, with fluconazole as a second-line option when the former is contraindicated. The addition of caspofungin or micafungin to first-line treatment remains debated. Systemic treatment is recommended in neonates with suspected congenital candidiasis who meet the following criteria [21]: those presenting with respiratory distress, clinical or laboratory signs of sepsis, a birth weight of less than 1,500 g, exposure to broad-spectrum antibiotics, extensive instrumentation during delivery, invasive procedures in the neonatal period, positive blood cultures, or an underlying immune deficiency. There is ongoing debate regarding the treatment of CCC in term neonates, as they have a low risk of systemic spread. The decision to initiate treatment in our asymptomatic patient was guided by the presence of multiple risk factors, including prematurity, very low birthweight, extensive colonisation, and prolonged intrauterine exposure. The duration of antifungal treatment should be at least 10 days. As an additional recommendation, some authors have suggested avoiding humidification in incubators to prevent fungal proliferation, particularly in neonates weighing less than 1,000 g [2].

Patient perspective

“It has been a very difficult time for me and my husband, it was our first child. We have been helped enormously by the Hospital Germans Trias i Pujol. Our daughter was born very healthy, she did everything without help, she’s now 6 months old and she is very healthy. We look very positively on the right decisions made by the doctors.”