Infective endocarditis (IE) is a microorganism infection of the heart endothelium (heart valves and endocardial membrane). Infective endocarditis is characterized by a typical lesion called vegetation, a mass of fibrin, and platelets with various shapes and sizes. Streptoccocus alactolyticus is a subspecies of S. bovis / Streptococcal equinus complex (SBSEC). This complex contains non-beta hemolytic streptococci and Lancefield group D streptococci, which are opportunistic pathogenic bacterial pathogens of human and animal digestive tracts. (1) Human infections caused by S. alactolyticus are sporadic. Kocuria is a gram-positive bacteria, actinobacteria in coccoid tetrads from the Micrococcaceae family, suborder Micrococcineae, order Actinomycetales. (2) Kocuria is often found in the oral cavity and normal skin in humans and other mammals. K. kristinae is known to cause catheter-related bacteremia and infection endocarditis.

Platelets have an essential role in the pathogenesis of endocarditis and are a sensitive monitor of systemic host responses to sepsis. (3) About 20-25% of patients with bacterial endocarditis have thrombocytopenia, even though it is usually mild to moderate. (4) However, very severe thrombocytopenia can be observed, which in some cases is associated with reactive platelet autoantibodies or syndromes that resemble thrombocytopenia purpura (TTP). Thrombocytopenia is one of the guideline criteria used by WHO as a potential indicator of clinical severity.

We report the case a 25-year-old female patient presenting with complaints of palpitation two weeks before admission. The patient was referred from a private hospital with a suspicion of IE. Initially, the patient had complained of fever arising six months ago, but it improved without medication. The patient complained of fever accompanied by nausea and vomiting during the next two months. At the time, the patient was admitted by a primary health care center and received paracetamol as medication. Reportedly, the patient’s complaints increased and the patient was diagnosed as allergic to paracetamol. The patient then went to a private hospital due to complaints of fever accompanied by palpitations and chest pain.

Physical examination showed that the general condition was good, with Glasgow comma scale (GCS) E4V5M6. Vital sign examination showed the following: blood pressure 90/70 mmHg, pulse 72 bpm regular, breathing frequency 20 x/minutes, and temperature 37.7 °C. Head and neck examination indicated there was slight anemia, no icterus, cyanosis, or dyspnea, and jugular venous pressure was not increased. Heart examination showed that there were apex grade III/VI systolic murmurs without gallop and extrasystole. Examination of the lungs, abdomen, and extremities were within normal limits. Electrocardiographic (ECG) examination found sinus tachycardia 119 bpm, normoaxis (Figure 1, A). Laboratory results showed Hb 9.1, leucocytes 9300, platelets 50,000, blood urea nitrogen 9.8, creatinine serum 0.9, glucose 238, K 3.4, Na 136, Cl 95, C3 16.4, C4 <6, IgG anti-dengue 4.3, and IgM anti-dengue 0.9. Urinalysis results showed nitrite+, protein 3+, leukocyte 2+. Chest radiography for cardiomegaly with 70% a cardio-thoracic ratio, and the lungs were within normal limits (Figure 1, B). From the results of the transthoracic echocardiography (TTE) (Figure 2):

The patient was diagnosed with possible IE, moderate MR, mild TR, thrombocytopenia pro-evaluation, normochromic normocytic anemia, and systemic lupus erythematosus (SLE) suspicion. As the initial therapy, we administered an intravenous (IV) infusion of saline 500 mL/24 hours, cefotaxime 3×1 g IV, gentamicin 1×150 mg IV, furosemide 2×20 mg IV, spironolactone 1×25 mg per oral (p.o.), lisinopril 1×5 mg p.o., bisoprolol 1×1.25 mg p.o.

The blood culture examination carried out at 3 locations with showed results positive for K. kristinae and S. alactolyticus, leading to the conclusion that they were bacteria isolated from 3 significant blood sample as infectious agents and true bacteremia. The blood cultures showed sensitivity to levofloxacin. The patient was diagnosed with definite IE and given levofloxacin 1×750 mg IV as a substitute for cefotaxime. Three days later, the platelets decreased to 20,000, and hypokalemia (potassium 2.6 mg/dL) was observed, and the patient was given additional therapy comprising potassium chloride 3×600 mg.

Transesophageal echocardiography (TEE) was performed (Figure 3), with the following results:

The patient was given an antibiotic and had a stable hemodynamic for two weeks while waiting for the scheduled surgery. On day 16 of hospitalization, the patient suddenly complained of abdominal pain and dyspnea. Systolic blood pressure decreased to 60-70 mmHg, and tachycardia, cold extremities, decreased consciousness, and lateralization to the right were observed. We provided hemodynamic support with norepinephrine 100 ng/kg BW/minutes and dopamine 5 mcg/kg BW/minutes up-titration, according to the hemodynamics. We prepare for intubation, but the condition worsened rapidly and the patient experienced cardiac arrest. We performed cardiopulmonary resuscitation, and the patient successfully return to spontaneously circulation two times, but she died during next two hours, with cause of death due to septic emboli.

Infective endocarditis is defined as bacterial, viral, or fungal microorganism infection on the endocardium, which can include one or more heart valves, endocardial murals, or septal defects. The most common infectious agents that cause infective valve endocarditis are gram-positive bacteria, including S. aureus, S. viridans, and enterococci.

Data indicate that Staphylococcus aureus is still the most common bacterial infection for all IE cases in developed countries (31%), followed by the Streptococcus viridans group (17%), staphylococci negative coagulase (11%), enterococci (10%), and SBSEC (6%). (1) Streptococcus still dominates in developing countries. Reports of cases of S. alactolyticus infection in humans are still infrequent. S. alactolyticus is reported to be a causative agent for IE complicated by septic embolism. Cekmen et al. reported a patient with aortic valve endocarditis obtained the presence of S. alactolyticus bacteremia from the culture. (1) On the other hand, there is a tendency for SBSEC bacteria to affect several heart valves, including prosthetic and mitral valves. The embolic events of SBSEC in IE range from 9% to 55%. (1)

K. kristinae is a gram-positive bacteria and is part of the normal flora of the oral cavity and human skin. Kocuria are widely distributed in nature. The genus has more than 18 species, but only five are known to be opportunistic pathogens. (5) There have been only six case reports of IE caused by K. kristinae. Studies that examine K. kristinae and IE are also very rare. The newest case report by Arif et al. reported a rare case of right-sided IE due to K. kristinae presenting with undiagnosed fever for 1 year. (6) In our case, the patient also had a history of prolonged fever that increase suspicion for K. kristinae infection. IE is a possible cause of a prolonged fever, especially in the presence of congenital heart disease. Antibiotic susceptibility is required for adequate therapy for Kocuria infection. Until now, there have been no internationally accepted guidelines for antibiotic treatment of IE caused by K. kristinae infection. (7)

Platelets are an essential component in pathogenesis of endocarditis. However, it is uncertain whether platelets may increase or limit disease progression. Thrombocytopenia tends to be a specific prognostic marker in endocarditis, rather than just a surrogate marker for acute phase reactions. (3) Platelets play an essential role in local defense against endovascular infections. (3) According to a study by Duran et al., thrombocytopenia is an independent predictor of death on days 1 and 8 of IE. (8) Thrombocytopenia in patients with IE has an essential clinical implication. Firstly, patients with thrombocytopenia must receive empirical anti-staphylococcal therapy because of the strong relationship between early thrombocytopenia and Staphylococcus aureus infection. (3) Secondly, thrombocytopenia can increase the risk of bleeding if anti-platelet agents are considered as adjunctive therapy. Thirdly, thrombocytopenia on day 8 indicates an impaired defense response to sepsis and predicts increased mortality. (3) Therefore, patients with thrombocytopenia may require more intensive monitoring, specific treatment, and, if relevant, surgical considerations.

In this case, we reported IE with bacteremia which resulted in culture showing S. alactolyticus and K. kristinae. Both are rare bacterial pathogens in IE. S. alactolyticus is a bacterium that can cause septic embolism, which can be associated with the poor outcome in this case. K. kristinae is a normal flora of flora on human skin but can be a pathogenic bacterium. K. kristinae is related to the condition of patients who are immunocompromised and to urinary tract infections in patients using urine catheters. However, urinalysis results were positive for bacterial infection. Thrombocytopenia is associated with a poor prognosis in patients with IE. So far there have been no descriptions in the literature the pathogenesis of the two pathogenic bacteria in this case with platelets depletion. Initial therapy in patients that are usually suspected of Staphylococcus aureus, as we administered in our case as well, is in the form of a broad-spectrum antibiotic, cefotaxime and gentamicin.

We reported a case of IE caused by rare bacterial pathogens, S. alactolyticus and K. kristinae, which were aggravated by the condition of thrombocytopenia. Further studies are needed in the management of IE relating to S. alactolyticus and K. kristinae as causative agents. Management of IE with thrombocytopenia requires caution since it is associated with poor outcomes. In this case, poor outcomes can be connected to the condition of thrombocytopenia coupled with the presence of specific bacteria, S. alactolyticus, which is known as bacteria that often causes septic embolism.