N. Naidoo, S. Foolchand, K. Swe Swe Han, K. Mlisana
Nireshan Naidoo, Senior pathology registrar, Department of Medical Microbiology, National Health Laboratory Service, University of KwaZulu-Natal, Durban
Serantha Foolchand, Specialist consultant, Feto-Maternal Obstetrics, Department of Obstetrics and Gynaecology, Inkosi Albert Luthuli Central Hospital, University of KwaZulu-Natal, Durban
Khine Swe Swe Han, Senior pathologist and consultant, Department of Medical Microbiology, National Health Laboratory Service, University of KwaZulu-Natal, Durban
Koleka Mlisana, Head of Department, Senior pathologist and consultant, Department of Medical Microbiology, National Health Laboratory Service, University of KwaZulu-Natal, Durban
A 22-year-old Para0 Gravida1 female with a dual valve prosthetic replacement, 2 years previously, presented at 8 weeks’ gestation for intravenous anticoagulation to prevent thromboembolic complications during the pregnancy. She was HIV seronegative, RH positive and RPR negative. Blood cultures (separate sites, over different days) cultured Acinetobacter baumanii with MIC’s susceptible to 4 antibiotic classes – beta lactam (piperacillin/tazobactam and meropenem), a fluoroquinolone (ciprofloxacin), an aminoglycoside (amikacin) and a polymyxin (colistin). Although transthoracic echocardiography revealed no prosthetic valvular abnormalities, subsequent trans-oesophageal echocardiography (TOE) showed early abscess formation around the posterior aspect of the aortic valve (AV) ring. She was not a candidate for surgical intervention was therefore managed conservatively.
Question 1: What is the most likely diagnosis? Give reasons to support your answer above.
Answer to Question 1 Infective endocarditis
According to Modified Dukes criteria, the patient has two major criteria.
1. Persistently positive blood cultures (at least 2 positive cultures of blood samples drawn >12 h apart or all 3 or a majority of ≥4 separate cultures of blood with first and last sample drawn at least 1 h apart) 2. Transoesophageal echocardiograph finding of abscess around the prosthetic valve ring.
Please refer to the AHA document for Modified Dukes criteria (reference 1) in order to answer MCQ questions.
While on combination treatment for Acinetobacter-related infective endocarditis (IE) with piperacillin/tazobactam and amikacin, the patient developed severe sepsis (involving organ failure) and septic shock necessitating ICU admission, ventilation and treatment with vasopressors for 29 days.
Treatment with combination antibiotic therapy was continued. However, after 4 weeks of combination therapy with piperacillin/tazobactam, MIC’s showed a creeping resistance pattern. The antimicrobials were stopped and meropenem was commenced (MIC remained sensitive). The patient did well on meropenem and in the fourth week of therapy, the blood cultures were negative for Acinetobacter spp.
Question 2: What is the clinical significance of Acinetobacter baumanii ?
Answer to Question 2
Acinetobacter is a Gram-negative coccobacillus that has emerged from being an organism of questionable pathogenicity to an infectious agent of importance in hospitals worldwide. The organism has the ability to accumulate diverse mechanisms of resistance, leading to the emergence of strains that are resistant to all commercially available antibiotics.
The epidemiology of Acinetobacter infections is broad and includes hospital-acquired infection, community-acquired infections in tropical environments, and infections that occur in the setting of wars and natural disasters. Some strains can survive environmental desiccation for months, a characteristic that promotes transmission through fomite contamination in hospitals.
Health care-associated infections tend to occur in debilitated patients in intensive care units (among both children and adults) and among residents of long-term care facilities (particularly facilities caring for ventilator-dependent patients). Additional risk factors include recent surgery, central vascular catheterization, tracheostomy, mechanical ventilation, enteral feedings, and treatment with third generation cephalosporin, fluoroquinolone, or carbapenem antibiotics.
More than 30 different species belonging to the genus Acinetobacter have been identified. Most of these species are environmental organisms and have not been associated with human disease. A. baumanii, A. calcoaceticus and A. lwoffi are the species most frequently reported in the clinical literature.
A number of factors contribute to Acinetobacter virulence:
The organism can survive under dry and iron-deficient conditions for long periods.
Approximately one-third of strains produce a polysaccharide capsule that works with the cell wall liposaccharide to prevent complement activation. The capsule may also delay phagocytosis.
Colonization in the lung is facilitated by the ability of Acinetobacter species to adhere to human bronchial epithelial cells using fimbriae. In addition, colonization of environmental surfaces is promoted by adhesion via pili and the subsequent formation of biofilms.
Hospital-acquired pneumonia and bloodstream infections are the most common infections associated with Acinetobacter. These Acinetobacter infections are associated with high mortality rates, partly because of prevalent comorbid conditions. Other less common infections include meningitis, wound or surgical site infections, and urinary tract infections.
The diagnosis of Acinetobacter infection is made by the growth of Acinetobacter from a patient specimen (e.g., sputum, blood, cerebrospinal fluid) in the setting of other clinical findings that suggest an infection at that site. Acinetobacter can colonize skin, wounds, and the respiratory and gastrointestinal tracts. It is important but may be difficult to distinguish between colonization and true infection, particularly since many infections occur in the setting of colonization.
Acinetobacter endocarditis: Acinetobacter species are a rare cause of infective endocarditis in native and prosthetic heart valves. In a study of 171 patients with prosthetic heart valve endocarditis resulting from nosocomial bacteremia, two cases were attributable to Acinetobacter. Acinetobacter endocarditis is characterized by an acute onset with an aggressive course. Mortality tends to be higher in the setting of native valve endocarditis than prosthetic valve endocarditis, likely because of the low index of suspicion leading to delayed treatment in such cases.
Blood cultures now grew Stenotrophomonas maltophila, sensitive to trimetroprim/sulfamethoxazole. This was most likely due to the selection pressure created by long term meropenem exposure as Stenotrophomonas is intrinsically resistant to carbapenems. Meropenem was discontinued because there was clinical improvement related to the IE and repeated TOE showed resolution of the AV ring abscess. She was commenced on high dose trimetroprim/sulfamethoxazole for 14 days.
Question 3: What is the clinical significance of Stenotrophomonas maltophila and when do we treat?
Answer to Question 3
Stenotrophomonas (Xanthomonas) maltophila is a ubiquitous, aerobic, non-fermentative, Gram-negative bacillus that is closely related to Pseudomonas species. It is a multi-drug resistant Gram-negative bacillus that is an opportunistic pathogen, particularly among hospitalized patients.
Pneumonia and bacteremia are the most common manifestations of infection. Less common manifestations of Stenotrophomonas infections include endocarditis, mastoiditis, peritonitis, meningitis, soft tissue infection, wound infection, urinary tract infection, and ocular infection. Stenotrophomonas infections have been associated with high morbidity and mortality in severely immunocompromised and debilitated individuals.
Risk factors associated with Stenotrophomonas infection include admission to an intensive care unit, HIV infection, malignancy, cystic fibrosis, neutropenia, mechanical ventilation, central venous catheters, recent surgery, trauma, and previous therapy with broad-spectrum antibiotic.
S. maltophila has inherent ability to adhere to foreign materials and form a biofilm, rendering protection from host defenses as well as antimicrobial agents. In addition, Stenotrophomonas has intrinsic or acquired resistance mechanisms to a number of antibiotic classes, including beta-lactams, aminoglycosides, carbapenems, and fluoroquinolones.
When to treat with antibiotics? It can be difficult to differentiate colonization from true infection due to Stenotrophomonas, although delay in appropriate treatment and use of inappropriate antibiotics can add to significant mortality. The decision regarding the need for antimicrobial therapy is based on a combination of clinical assessment and culture data.
We suggest trimethoprim-sulfamethoxazole (TMP-SMX) for treatment of infection due to Stenotrophomonas (Grade 2C). The duration of therapy depends on the site of infection. Other agents with in vitro activity against Stenotrophomonas include ceftazidime, ticarcillin-clavulanic acid, levofloxacin, moxifloxacin, minocycline, tigecycline, polymyxins (ie, colistin sulfate), and rifampin.
The patient remained in the care of obstetrics until the baby was delivered via elective Caesarian section with no maternal or neonatal complications. Both mother and child are clinically well and the patient is being followed up by the cardiologists.
Question 4: What are the current thoughts on prophylaxis for bacterial endocarditis?
Answer to Question 4
Routine antimicrobial prophylaxis for bacterial endocarditis is not recommended in most women with valvular heart disease during pregnancy and delivery. However, the 2008 American College of Cardiology/American Heart Association guidelines for the management of adults with congenital heart disease suggests that in select high-risk patients, such as those with prosthetic heart valves, it is reasonable to consider antibiotic prophylaxis before vaginal delivery at the time of membrane rupture. Antibiotic prophylaxis to reduce the risk of postpartum endometritis is routinely given prior to all cesarean deliveries, and will provide protection against endocarditis as well.
The AHA guidelines state that a very small number of infective endocarditis are prevented by antimicrobial prophylaxis following dental procedures and should be given only in high risk patients eg those with prosthetic valves. Procedures include those involving manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa. Prophylaxis is not routinely recommended for patients undergoing a genitourinary or gastrointestinal tract procedure.
Please refer to reference 7 for further information.
Question 5: What is the role of Antimicrobial stewardship and the Microbiology laboratory in such patients?
Answer to Question 5
A rapid microbiological service is essential for an antimicrobial stewardship programme to be effective. The use of broad spectrum antibiotics can be limited if susceptibility results are available timeously. In this case, the carbapenem was only used when the MIC to piperacillin/tazobactam increased. It is imperative to monitor antimicrobial MIC’s when patients are on long-term antibiotic cover in order to detect resistance and institute timeous antibiotic changes. Active collaboration and effective communication between pathologists and obstetricians is central to the patient’s care. Clinical microbiology and diagnostic services must be available 24 hours for such high-risk patients.
1. Baddour LM, Wilson WR, Bayer AS et al. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation. 2015;132:1435-1486. DOI: 10.1161/CIR.0000000000000296.
2. Fournier PE, Richet H. The epidemiology and control of Acinetobacter baumannii in health care facilities. Clin Infect Dis 2006; 42:692.
3. Joly-Guillou ML. Clinical impact and pathogenicity of Acinetobacter. Clin Microbiol Infect 2005; 11:868.
4. Paez JI, Tengan FM, Barone AA, et al. Factors associated with mortality in patients with bloodstream infection and pneumonia due to Stenotrophomonas maltophilia. Eur J Clin Microbiol Infect Dis 2008; 27:901.
5. Denton M, Kerr KG. Microbiological and clinical aspects of infection associated with Stenotrophomonas maltophilia. Clin Microbiol Rev 1998; 11:57.
6. Calza L, Manfredi R, Chiodo F. Stenotrophomonas (Xanthomonas) maltophilia as an emerging opportunistic pathogen in association with HIV infection: a 10-year surveillance study. Infection 2003; 31:155.
7. Wilson W, Taubert KA, Gewitz M. Prevention of Infective Endocarditis: Guidelines From the American Heart Association: A Guideline From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation 2007;116;1736-1754; originally published online Apr 19, 2007;(DOI: 10.1161/CIRCULATIONAHA.106.183095)
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