We present 15 cases of streptococcal sepsis complication treated in a PICU setting. Pneumococcal sepsis patients have not been considered in this series. The rarity of the clinical presentation warrants comments regarding both the occurrence and the intensive care approach. Epidemiological and intensive care management issues are discussed on a group-by-group basis.
Regarding Streptococcus agalactiae (GBS), following the CDC 2002 Guidelines recommending a universal screening for maternal rectovaginal GBS colonisation at 35–37 weeks of gestation, a clear change in the epidemiology of S. Agalactiae occurred, with a marked decrease in the prevalence of early onset GBS disease (2.0 per 1000 live births in 1990; 0.6 per 1000 by 2001–2002; 0.3 per 1000 in 2004) [2,3,4]. On the other hand, only a mild modification of the late-onset disease incidence was registered during the years 1996–2004 in the UK and, for the first time in 2003, the rate of late-onset disease overcame the one of early-onset disease [5, 6]. Cerebrovascular complications induced by S. Agalactiae late-onset sepsis are not well described, though an increased prevalence of meningitis is acknowledged. The occurrence of cerebral arteries thrombotic/ischaemic lesions and cerebral venous sinuses thrombosis in association with a purulent meningitis/septic shock have been described elsewhere, but they were rarely caused by neonatal Streptococcus agalactiae (group B streptococcus, GBS) infection, as in the present series. A rapidly progressive thrombotic occlusion of cerebral venous sinuses is associated with fatal cerebral vascular tamponade. Clinical suspicion is of paramount importance, while head CT scan may result falsely negative in up to 16% of patients [7]. The emergency intervention is aimed at maintaining venous outflow patency, despite the impending risk of intracranial bleeding. Despite the risk of further hemorrhagic complications, intravenous unfractionated heparin (UFH) anticoagulation in association with antithrombin replacement was performed because of severe compromised cerebral condition. The neonate also needed cardiorespiratory support to improve cerebral perfusion. Protein C, protein S and antithrombin deficiency are known causes of thrombosis. However, it is more likely that depressed levels of protein C, protein S and antithrombin in our patient were related to the early consumption of these factors by the acute cerebral venous infarction and/or by the septicaemic state, rather than a cause of thrombosis. No randomised controlled trials in infants and children could support such a therapeutic choice, and even in adults there is no clear evidence [8, 9]. Consequently, despite the cerebral venous bleeding, a schedule of UFH followed by a 3-month course of low-molecular-weight heparin (LMWH) was given [7, 10]. In a large multicenter Canadian study, the incidence of cerebral sinovenous thrombosis (CSVT) was 0.67/100,000 children/year, 43% of whom were under 1 month of age; CSVT may cause cerebral venous infarction and hemorrhage because of occluded venous outflow. As a whole, prothrombotic risk factors are present in 39 to 54% of cases.
Regarding Streptococcus faecalis, literature highlighted a rising incidence of enterococcal infections during the last years, not only among adult patients but also among hospitalised patients of neonatal/paediatric intensive care and onco-haematological units [11,12,13,14]. Although many genetically different subtypes have been identified, E. faecalis and E. faecium represent the two main species causing most human enterococcal infections. These agents represent a large group of gram-positive natural inhabitants of the human gastrointestinal tract: possible clinical presentations of enterococcal infection include intra-abdominal infections, endocarditis, primary bacteremia, urinary tract infections and, less frequently, pneumonia, meningitis and osteomyelitis (especially in immunocompromised hosts). Only a few cases of E. faecalis thoracic empyema have been reported in adults. The occurrence of enterococcal sepsis followed by a pleural empyema in a previously healthy child is almost exceptional. Although enterococcal empyema is rare, its occurrence has been previously linked to intra-abdominal infections, and it is associated with a high mortality (41%) [15]. Numerous evidence shows that the majority of enterococcal-associated infections of the lower respiratory tract have a complicated course, including the development of lung abscess, pleural empyema, respiratory failure and cardiovascular instability. Therefore, Enterococci should be considered as potential cause of severe, unresolved pneumonia. It appears of importance to avoid a prolonged course of invasive mechanical ventilation following a high-intensity antibiotic therapy. For this reason, in the case reported above, following the VATS procedure, we decided to introduce the NIV technique early, to minimise the risk of pulmonary-systemic superinfections.
Viridans streptococci (VS) represent a heterogeneous group of streptococcal species, which are part of the normal flora of human oral cavity, gastrointestinal tract and female genital tract. Infections usually result from spread of the organisms outside their normal habitat. Strains of Viridans streptococci are known to be the most common etiologic agents in bacterial endocarditis, mainly in patients with abnormal cardiac structure [16, 17]. Immunocompromised patients with VS bacteremia may develop shock, rash and respiratory distress similar to ARDS. VS may account for up to 25–30% of bacteremic episodes in patients with malignancies; VS bacteremia should be suspected in neutropenic children, especially in the presence of mucositis [18, 19]. Viridans streptococci shock syndrome (VSSS) has been defined as hypotension requiring inotropic support [20]. VS have been frequently described as a cause of bacteremia, and VSSS develops in up to 18% of VS bacteremia in children with cancer or SCT recipients. Infection of immunocompetent individuals is generally rare [21]. Although primary pneumonia due to Viridans streptococci has rarely been described, published reports documented recovery of these organisms in specimens of empyema and lung abscess, whereas VS septicaemia appears exceptional [22,23,24]. We observed a severe cardiac involvement with septic shock and consumption coagulopathy due to VS infection. Cardiac function impairment resembling a “cardiac stunning” picture is rarely present at onset of septic shock. In the two patients reported, after failed initial preload optimisation and dobutamine titration, a inotropic rescue with enoximone/milrninone was performed. These agents selectively inhibit phosphodiesterase III isoenzyme in both cardiac and vascular muscle, which is necessary for the breakdown of 3′5′-cyclic adenosine monophosphate (cAMP) [25]. Due to the severity of clinical presentation, recombinant APC infusion was started, achieving coagulative status control [26]. Though S. Viridans represents a known agent of infective endocarditis, a severe sepsis complicating pneumonia with cardiac valve involvement is unusual. All patients were empirically treated with third generation cephalosporins and amikacin before susceptibility testing was available, and recovered without complications.
Concerning Streptcoccus Pyogenes invasive disease, an increased incidence has been reported during the last years [27]. The incidence of invasive S. Pyogenes disease in Italy is 0.38/100,000 (3/100,000 in Europe), with most cases among older patients (only 24% of cases in the 0–17 years old group) [28]. Overall, 8% of patients with Streptococcus Pyogenes infection develop necrotizing fasciitis and 13% evolve to streptococcal toxic shock syndrome (STSS), with an incidence rising to 50% among cases of necrotizing fasciitis. The only clinical manifestation showing a higher prevalence in children < 10 years old is meningitis (2% of overall cases). Invasive group A Streptococcus (GAS) infections have been reported in all age groups, including sepsis, bacteremic pneumonia, puerperal sepsis, septic scarlet fever, scarlatina maligna, erysipelas, necrotizing fasciitis, gangrene, myositis and streptococcal toxic shock syndrome [29,30,31]. A rapid and fatal course has been described even in the immunocompetent host, with a mortality rate of 7-58% [32]. Several risk factors have been associated with invasive GAS infection, in particular VZV co-infection and the use of nonsteroidal anti-inflammatory drugs [33]. Though invasive GAS infections are alarmingly increasing worldwide, an acute respiratory distress syndrome caused by GAS has been rarely described in pediatrics. Despite non-staphylococcal pneumatoceles being described in childhood, reports of GAS pneumatoceles are extremely rare. In our case, a GAS pneumonia and pleural empyema rapidly progressed to ARDS. Pneumothorax and a broncho-pleural fistula complicated the ventilatory management. Failing of conventional therapies (gentle conventional ventilation, surfactant instillation) led to the adoption of a single lung ventilation. Apart from surgical indications, lung isolation may be appropriate even in unilateral lung disease (e.g., lung abscess, bronchopleural fistula, severe one-sided bullous disease, pulmonary hemorrhage) [34,35,36]. In children, due to the small tracheal dimensions, balloon-tipped bronchial blockers, wire-guided endobronchial blocker, UniventTM tubes, double-lumen tubes and selective mainstem bronchial intubations with a conventional endotracheal tube may be chosen [37,38,39]. Single lung ventilation is often complicated by the persistent collapse of the unventilated lung and by the obstruction of the right upper lobe in case of right-sided intubation. For these reasons, only time-limited applications can be recommended. In our case, a 36-h single lung ventilation resulted a safe procedure and allowed bilateral lung ventilation restoration. Unilateral lung disease represents a challenge in ventilatory management because of the asymmetry in lung mechanics. Conventional support may fail to produce adequate gas exchange and may cause further deterioration. In those circumstances, independent lung ventilation allowing different mean pressures in each lung may represent a valid strategy. Alternatively, the most compromised lung may be treated with HFOV, while the contralateral is conventionally supported. In children, due to the small tracheal dimensions, unilateral lung ventilation may represent a valid alternative.
