We report a case series of fatal invasive diseases due to Staphylococcus caprae. We describe the first cases of S. caprae sepsis in two italian patients. In the first patient there was also evidence of the fourth case reported in the English language literature of mitral endocarditis. We also discuss the main features of differential diagnosis on the basis of a literature review.
Staphylococcus caprae, Coagulase-negative Staphylococcus, Infective endocarditis, Staphylococcal sepsis, Fatal brain thromboembolism, Native valve endocarditis
Staphylococcus caprae belongs to the broad family of coagulase-negative Staphylococci (conS), and is a potential colonizer of human skin. Initially isolated from goat milk, its has been sufficiently characterized from a bacteriological point of view since the year 1995 [1-11], although some unexpected features like the possible production of S. aureus-like enterotoxins deserve further studies [7,12,13].
Although showing a mild virulence potential, its biofilm (slime) production and its unpredictable antimicrobial susceptibility profile [2,4,5] make it a rare, but challenging pathogen especially in nosocomial settings [11,14-16] or when prosthetic devices are of concern, with bone and joints as the most frequently reported localizations [1,6,10,17-22].
Although sporadic episodes of otitis, mastoiditis, meningitis, endophthalmitis, urinary tract infection, pneumonia, and peritonitis have been described, usually after surgery or interventional procedures, as well as very infrequent cases of sepsis or bacteremia remain very rarely reported (Table 1) [23,24]. Reports of endocarditis are even more rare [24,25], and are usually related to prosthetic valves or implanted electronic devices (IED). The only report of S. caprae native valve mitral endocarditis is that described by Kwok, et al. [25].
Table 1: Isolation of Staphylococcus caprae from blood cultures. View Table 1
A 68-year-old male suffering from a compensated type 2 diabetes mellitus and multiple comorbidities (COPD, diabetes-related nephropathy and a previous CNS vascular disease with severe neurologicals remnants including hemiplegia and dysarthria), accessed the Emergency Room of our Hospital due to altered mentation, low back pain, and an overwhelming acute heart failure with pleural-pericardial effusion. A transesophageal chest ultrasonography disclosed an endocarditis with 1.5 cm diameter vegetation on a trilobated valve, conditioning a severe left atrial-ventricular dysfunction (ejection index 40%). A CNS scan did not show further abnormalities, when compared with the previous one obtained 7 months before. Routine laboratory examinations addressed a moderate leukocytosis with neutrophilia, and increased serum C-reactive and procalcitonin levels (65.9 mg/dL and 0.97 ng/mL respectively). Multiple consecutive blood cultures allowed the growth of Staphylococcus caprae, while urine cultures tested negative. The microbial strain proved phenotypically susceptible to clindamycin, daptomycin, rifampicin, tetracycline, glycopeptides, linezolid, tigecycline and cotrimoxazole, and resistant to oxacillin, gentamycin, erythromycin, and levofloxacin. A diagnosis of defined aortic endocarditis was therefore posed, according to the modified Duke criteria. A SARS-CoV-2 disease was excluded, and the surveillance nasal and rectal swabs proved negative for colonizations. Combined i.v daptomycin (at 350 mg day), plus tigecyclin at 100 mg/day after a 100 mg loading dose), were started plus supportive therapy. A concurrent spondilodiscitis was excluded by a MRI examination of the spine, while a brain MRI scan did not show signs of metastatic infectious foci. Both ophtalmologic and odonto-stomatologic consultancies were recommended, together with the appropriate instrumental assessments. After the 6-week attack antibiotic therapy, a de-escalation schedule based on oral rifampicin-tetracycline therapy was suggested, but our patient did not survive an acute-on chronic heart ischemic attack, when still hospitalized at the intensive Cardiology Unit of our Hospital.
A 54-year-old male already suffering from a macrocephaly due to an Arnold-Chiary syndrome and a permanent ventriculo-peritoneal shunt, experienced an acute subarachnoideal hemorrhage after a head trauma occurred at home. Through the Emergency Room he was hospitalized at the Neurosurgical Department of our Hospital, where he received neurosurgical decompression of a large right temporal subdural hematoma, confirmed by a brain CT scan, which also allowed a correct positioning of a cranial drainage. Laboratory assessment obtained upon admission did not show relevant abnormalities save a moderate increase of serum creatinkinase level (404 U/L), related to the recent trauma. Oral, nasal, and rectal surveillance swabs tested negative for all searchable microorganisms, while blood culture repeatedly yielded S. caprae, which proved susceptible to all tested antibiotic compounds. Intravenous dexamethasone, mannitol, furosemide therapy was immediately started to contain brain edema, together with phenobarbital-levetiracetam to prevent seizures. The standard preoperatory antibiotic prophylaxis with cefazolin was followed by co-amoxiclavulanate, and subsequently switched to linezolid at 600 mg/d, which guarantees an excellent brain penetration. Despite neurosurgery and the intensive management, our patient went to death after 5 sole days since hospitalization.
The first described case is extremely challenging due to: its clinical differential diagnosis with arterial coronary disease [22] and spondylodiscitis [18], both rare but already described occurrences in the setting of S. caprae infection. Both complications have been expected by us, but were carefully ruled out in our patient with appropriate clinical and instrumental examinations. The neurological signs and symptoms following the thromboembolism from the ascertained aortic endocarditis were more difficult to be recognized timely, due to the concurrent, severe remnants of our patient who already had a very high risk of ischemic heart-cerebral disease. They were hindered by the sequelae of a previous stroke documented by appropriate imaging techniques.
Moreover, both the potential nosocomial source and bacterial colonization, both frequent underlying conditions in other studies [4,5,8,9,11,15,16,24,25], and the resort to invasive procedures as frequent proxys for S. caprae disseminated human disease, were excluded or absent in our setting, respectively.
Other interesting aspects which deserve further investigation are those related to colonization and intra species competition of S. caprae with other Staphylococci on the human skin, especially in hospital settings [4,5,8,9,16,26], an those related to the in vivo antibiotic effectiveness [1,4,5,8], which could not be addressed in our patient, because of his death due to an acute-on chronic heart failure. It is conceivable that our second patient described for a severe and fatal S. caprae sepsis contracted the staphylococcal infection during his hospitalization, as this bacterium has been implicated in several nosocomial infections [23]. Together with the case described here, three of four isolations of S. caprae from blood cultures were associated with cardiac malformations or endocarditis [1,24,25]. In a Indian study performed to speciate coagulase-negative staphylococci (CoNS) and their antibiotic susceptibility pattern isolated from clinical samples, among the 120 consecutive CoNS strains isolated from various clinical samples, S. caprae accounted for 5% (6 isolates) of all isolates (4, 66.6%, from blood). All S. caprae isolates from this study were susceptible to doxycycline, linezolid, and teicoplanin, and vancomycin. The resistance percentage to ciprofloxacin, gentamicin and cotrimoxazole was 33.33%. The highest methicillin resistance was in S. caprae (66.67%), S. epidermidis (64.71%), S. lugdunensis (57.1%) [28].
In one other study evaluating the ability of automated ribotyping to identify isolates of CoNS species obtained from the blood of hospitalized patients during a 4-year period, among 177 CoNS isolates, the collection of clinical isolates comprised 3 isolates of S. caprae [29].
In conclusion, we briefly report and discuss a unique case of native valve aortic endocarditis due to S. caprae, the only complicated by a lethal cerebral thromboembolism, in absence of colonization and resort to surgery or invasive procedures. Also S. caprae should be considered in the setting of severe, complicated, and potentially lethal endocarditis, and prevention measures like colonization screening promoted in hospital settings.
All the authors contributed to the clinical evaluation of the cases and to the drafting of the manuscript.
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A signed informed consent for publication was obtained, and the manuscript is in accordance with the institution's ethics committee.