Abstract
Micrococcus luteus (M. luteus) is a Gram-positive microorganism that typically dwells in environments such as soil, water, and human skin, hence, entitling it as a contaminant organism. However, there are instances where M. luteus affects immunocompromised patients, such as in infective endocarditis and septic arthritis, but typically among immunocompromised patients. However, an evolutionary change has been observed in the infectious capability of this organism especially with reports emerging on its instance among immunocompetent population. A 68-year-old female presented to the emergency medicine department with complaints of persistent fever and neck soreness. Patient’s blood culture reports were positive for M. luteus and owing to her history of undergoing prosthetic valve replacement. A preliminary diagnosis of prosthetic valve infective endocarditis was made. However, since M. luteus was a typical skin contaminant, and its infective etiology was limited toward immunocompromised patients, blood cultures were repeated for confirmation. Repeat blood cultures ascertained the suspicion of M. luteus; hence, treatment with intravenous vancomycin was initiated. Patient was discharged after 8 week of treatment following complete eradication of infective markers and symptomatic improvement. Here, we report the novel occurrence of prosthetic valve infective endocarditis, by a typically contaminant organism, in an immunocompetent individual, hence, raising concerns on the evolutionary changes in the organism, M. luteus.
Plain language summary
Micrococcus luteus is a type of bacteria usually found in the environment—such as in soil, water, and even on human skin. Because it’s so common, doctors often consider it a harmless contaminant when found in lab samples. In rare cases, it can cause serious infections, but mostly in people with weakened immune systems. In this case, we describe a rare infection in a woman in her late 60s who had a prosthetic heart valve. She came to the hospital with fever and neck pain. Her blood tests repeatedly showed the presence of M. luteus, and based on her symptoms and medical history, doctors diagnosed her with a serious heart infection called prosthetic valve infective endocarditis. Although M. luteus is usually not considered a harmful germ in healthy people, this case suggests it may be changing and becoming more dangerous. The patient received an 8-week course of IV antibiotics (vancomycin), improved, and was safely discharged. This case highlights a possible shift in how this usually harmless bacterium behaves and stresses the need for increased awareness—even among patients with healthy immune systems.
Introduction
Prosthetic valve replacement trends have gained much attention in recent years with data, from 2009, indicating close to 280,000 procedures being performed worldwide every year. 1 With current trends, it is predicted that by the year 2050, close to 850,000 prosthetic valve replacement (PVR) would be performed annually. 2 This increase in the number of PVR is largely attributed to changing patient demographics, specifically, an increase in global geriatric population with higher incidences of heart valvular diseases, improved awareness and screening, and advancements in scientific technologies with availability of newer types of valves in the global market.3,4 The utilization of PVR in the treatment of valvular diseases is not free of risk. Complications following the intervention include an increased risk of developing thromboembolism, structural valve dysfunctions, and anticoagulation-related complications.5,6 A potentially significant risk is the development of prosthetic valve infective endocarditis (PVIE) which is a complex interplay modulated by combination of microbial, procedural, and patient-related factors. The risk of PVIE, post-valve replacement, increases from 5% to 20% and the incidence ranging between 0.5 and 1.0 per 100 person-years. 7 The shift in pathogens such as coagulase-negative staphylococci (CoNS) and methicillin-resistant Staphylococcus aureus (MRSA)—it’s virulence, nosocomial infections, patients with advanced heart failures, prior history of endocarditis, increasing age, and antibiotic resistance contribute as risk factors to developing PVIE. 8 The typical microorganisms causing infective endocarditis (IE) are Streptococcus species, Kingella species, Haemophilus species, Aggregatibacter species, and community-acquired Enterococcus species. 9 An atypical opportunistic organism, called Micrococcus luteus (M. luteus), is gaining attention in causing PVIE worldwide.9,10 A tertiary care center study by Zhu et al. 11 identified an increasing trend in incidence of M. luteus from zero to 12.6 per 100,000 (2010–2019). To date about 22 cases of M. luteus-induced IE has been reported worldwide, with 18 cases on prosthetic valves and 4 cases on native valve. 10
M. luteus has a distinct ability to primarily affect immunocompromised patients, which were evident in all cases of IE reported to date.10,12 However, with the case reported by Guillermo et al., 12 on M. luteus affecting an immunocompetent individual patient for the first time, the alarming possibility of an evolutionary adaptation within these contaminant microbial species was suspected. Here, we report another case of Micrococcus species-induced PVIE in an immunocompetent patient from a tertiary care health center in India.
Case presentation
A 68-year-old female presented to the emergency medicine department of the hospital with complaints of fever and persistent neck soreness for 1 week. She had a past medical history of hypertension, hypothyroidism, coronary artery disease, and cervical radiculopathy. She also had a surgical history of coronary artery bypass graft and prosthetic aortic valve replacement (PAVR) with bioprosthetic valve 4 years ago. She was regularly on oral antihypertensives, thyroxine, antiplatelets, statins, and neuropathic pain medications, prior to presentation. She had no alcohol or smoking history.
Upon admission, her initial evaluation revealed her blood pressure of 160/88 mmHg, body temperature of 102.5°F, pulse rate of 110 beats per minute, and respiratory rate of 23 breaths per minute. Physical examination revealed mitral regurgitation; soft blowing holosystolic high-pitched murmur, of grade 1/6 located at the fifth intercostal space, and midclavicular line with radiation to the left axilla, best heard in the left lateral decubitus position and tricuspid regurgitation; soft, blowing, high-pitched, holosystolic murmur, of grade 1/6 located at left lower sternal border between fourth and fifth intercostal space best heard in supine position. No cutaneous manifestations resembling petechiae, splinter hemorrhages, Osler nodes, or Janeway lesions were identified. Chest radiography was normal. Electrocardiogram findings revealed features of atrial fibrillation. Two-dimensional echocardiogram and transesophageal echocardiography (TEE) revealed mild concentric left ventricular hypertrophy, grade two diastolic dysfunctions, mild-to-moderate pericardial effusion and an echogenic structure (with independent mobility of size 0.5 × 0.5 cm) attached to prosthetic aortic valve. Owing to the patient’s history of PAVR, 4 years back, possible PVIE was suspected, with imaging providing confirmation for the same.
Blood investigations revealed infectious markers such as C-reactive protein (CRP) and procalcitonin levels of 261.56 mg/L and 7.94 ng/mL, respectively. Following suspicion of PVIE, as per 2023 Duke International Society of Cardiovascular Infectious Disease (Duke-ISCVID) criteria, three sets of blood cultures, one aerobic and one anaerobic each, from three different vascular access sites were evaluated for microbial growth. 13 Blood culture results revealed M. luteus, resistant to clindamycin (minimum inhibitory concentration (MIC) ⩾ 4 mg/L), erythromycin (MIC ⩾ 8 mg/L, and penicillin-G (MIC ⩾ 0.5 mg/L) and sensitive only toward vancomycin (MIC ⩽ 0.5 mg/L). Repeat blood cultures were sent upon suspecting possible skin contamination, which was also positive for M. luteus.
Initial presentations resembled an underlying infection and owing to the patient’s history of PAVR and echocardiogram findings confirming vegetations, and PVIE was suspected. With repeat blood cultures confirming M. luteus, ruling out possible contamination, and with case reports existing on M. luteus causing PVIE, the possibility of M. luteus-induced PVIE was considered. Furthermore, according to the 2023 Duke-ISCVID criteria, our patient had satisfied two major (TEE revealing vegetation and positive blood cultures sets) and a minor criterion (prosthetic valve history and persistent fever > 100°F) reinforcing the initial diagnosis from possible PVIE to definite PVIE.
On suspecting a possible bacterial infective etiology, patient was empirically started on intravenous piperacillin—tazobactam 4.5 g thrice daily. Upon suspecting PVIE, with imaging reports suggestive of valvular vegetation, intravenous vancomycin 1 g twice daily was added along with piperacillin—tazobactam 4.5 g for empirical Gram-positive coverage on day 1. Other supportive medications such as intravenous fluids, antipyretic medications, and her regular medications were continued. With initial blood culture reports (Day 3 of admission), positive for M. luteus, sample contamination was suspected, and repeat cultures were sent. Since vancomycin was among the treatment choice for M. luteus, same antibiotics was continued while awaiting repeat blood culture reports. Vancomycin trough level was measured 30 min prior to the administration of fourth dose on day 2, which was at 14.8 μg/mL; hence, no dose adjustment was made.
Following 5 days of treatment, patient started improving symptomatically. Her fever episodes reduced and infection markers such as CRP, procalcitonin, and white blood cell counts was also decreasing. Repeat blood culture (day 5 of admission) reports was again positive for vancomycin sensitive M. luteus, thereby reinforcing the diagnosis of M. luteus-induced PVIE. Intravenous piperacillin—tazobactam 4.5 g was stopped on day 5, as it had no sensitivity and coverage toward M. luteus, and vancomycin was continued. Three sets of blood cultures were repeated once in every 48 h till the infection was cleared. Routine monitoring of complete blood counts, serum creatinine, and infection markers was done for evaluating treatment progress and vancomycin-induced nephrotoxicity. All possible drug interactions and adverse drug reactions possibilities with vancomycin treatment were assessed during the course of treatment.
After 2 weeks of treatment, repeat three sets of blood cultures were free of organism, and hence, vancomycin was continued for 6 more weeks as per American Heart Association (AHA) guidelines recommendation for IE management. 14 Our patient had received treatment for a total of 8 weeks, and blood cultures were repeated weekly. Blood cultures and TEE was repeated at eighth week, which were free of any organisms, and a stable valve with no features of vegetation, and hence, she was discharged and advised to be evaluated in outpatient basis. She further had no symptomatic presentations and clinically stable.
Discussion
M. luteus is a Gram-positive coccus belonging to the genus Micrococcus in the family Micrococcaceae, commonly found as a contaminant in natural environments and on human skin. 11 Micrococcus species are typically and often interpreted as skin contaminants; however, there are emerging evidences on Micrococcus species inducing blood stream infections, highlighting the capability of these organisms to be a definitive pathogenic. 11 A distinct characteristic of all cases with M. luteus infection is that they occur in immunocompromised patients, or those with indwelling catheters, medical devices, or have undergone any invasive surgeries.11,15 This shows the opportunistic infection capability of M. luteus species among immunocompromised population.9,10
However, the first case reported by Rodriguez-Nava et al. on M. luteus causing PVIE in an immunocompetent patient, the typical infective pattern of this organism raised questions within the scientific community. 12 This raises concern regarding the organism’s adaptability in affecting immunocompetent patients rather than its usual target of immunocompromised population. Here, we report the second emergent case, from a low-to-middle income country, on M. luteus-induced PVIE in an immunocompetent patient.
The capability of Micrococcus species to cause PVIE depends upon the organism’s ability to form a biofilm within the prosthetic valve. Biofilms are formed in surfaces usually on medical devices such as prosthetic valves, intrauterine devices, catheters. The biofilm is a symbiotic environment where the microorganism colonises within the surface of medical device and poses a risk for blood stream infection. M. luteus uses the same mechanism and survives by forming biofilms on the prosthetic valve. Interestingly, native valves are also now targets for M. luteus for infection.9–12,15,16 In our case, the history of PAVR was a risk factor for developing PVIE. Figure 1 represents how M. luteus affects individuals and the process of biofilm formation.
Process of biofilm formation with M. luteus infection.
The diagnosis of Micrococcus species is also challenging owing to the organism being a typical skin contaminant. Dargère et al. 17 stated that Micrococcus species are one of the most common skin contaminant isolated from blood cultures. Hence, a diagnostic conundrum is generated on whether a contaminant species should be treated if found in blood. This depends on the clinical judgment, blood culture reports, bacterial growth rates, and novel microbiological techniques to prevent sample contamination. 11 In our case, we ruled out the possibility of skin contamination by repeating blood cultures from different sites to affirm M. luteus-induced PVIE.
The lack of diagnostic and treatment guidelines is also a challenge posed. The AHA and Infectious Diseases Society of America provides guidelines on management of IE; however, does not encompass M. luteus as a possible organism capable of PVIE.9,13 Due to the dearth of data on M. luteus, we followed a modified evidence-based approach of utilising current existing reports and guidelines of PVIE for the management in our case.
The antibiotic of choice for Micrococcus infections are vancomycin and rifampin owing to its excellent biofilm penetration.9,10 However, we used only vancomycin based on antibiotic susceptibility testing and based on the clinical response toward the treatment. To confirm complete infection eradication repeat blood cultures were done until found negative and at the end of treatment. 14
Based on data from current existing literatures, to date about 18 cases of M. luteus-induced PVIE, and four cases of M. luteus-induced native valve IE have been reported. 10 Only a single case has been reported on M. luteus-induced PVIE, in an immunocompetent patient, from the United States (Table 1). 12 Our case adds to the list of Micrococcus infestation in an immunocompetent individual, thereby raising questions on the change of infectious pathology of the microorganism.
Existing literature on M. luteus-induced PVIE.
PVIE, prosthetic valve infective endocarditis.
Conclusion
M. luteus is a typical skin contaminant organism commonly infecting immunocompromised individuals; however, with emergent reports on PVIE induced by Micrococcus species, among immunocompetent individuals, there is a rising concern among microbiologists and infectious disease specialists regarding a change in the infection pattern. Our case adds to the list of cases on Micrococcus-induced PVIE among immunocompetent population thereby questioning the adaptability and natural selection of this rare organism.
