Here is a fascinating study on Bartonella endocarditis. It is extremely difficult to pick up because of a 20% sensitivity rate on standard blood cultures. One possible solution?
Next generation sequencing:
"Next Generation Sequencing (NGS) of microbial cell free DNA (mcfDNA) is a new and emerging diagnostic test. This method is noninvasive with a short turnaround time (28 h), detecting the normal products of bacterial turnover within the body. When we compare the turnaround time to serology, NGS and IFA are almost equal, adding in two to four days for NGS specimen shipping. As the test becomes more readily available, this should improve. The NGS test relies on sequencing mcfDNA in circulating plasma to identify over 1000 pathogens (including bacteria, fungi, viruses) and reports a quantitative amount as molecules per microliter (MPM). In one study, NGS reported a 95% sensitivity in culture positive endocarditis even with antimicrobial pre-treatment [3]... "
Bartonella is the leading cause of culture negative endocarditis in the US [9] and second most common CNE pathogen worldwide [4]. The species typically infects native valves with the aortic valve being the most commonly reported [4]. Prosthetic valve infections have been described, with clinical presentations that are usually severe with rapid progression to heart failure. Rarely, cases of myocarditis associated with B. henselae and B.quintana infections have been reported. Some reports resulting in sudden unexpected cardiac death in previously healthy individuals [2]. About 70% of patients require valve replacement secondary to severity of valve damage [10]. Mortality remains low at 7% [10]. Various reviews of pathology found histologic findings such as fibrosis, endothelial proliferation and neovascular formation that were distinctive to Bartonella [11], [12], [13]. The suggestion is for higher calcification and less extensive vegetation material, indicating a more chronic inflammatory process [12]. These findings are supportive of the need for surgical intervention in addition to antimicrobials for clearance rather than medical management alone.
Renal failure is a common manifestation of Bartonella endocarditis, with one study estimating greater than 40% of patients present with such findings [14]. Specifically, rapidly progressive renal failure is noted to be a clinical feature in infection-associated glomerulonephritis (GN)."
We have seen many cases of active Bartonella in LD patients (although none with known endocarditis and renal failure) and in our practice it is the most difficult IC pathogen to eradicate to date. The studies below imply that use of macrolides, gentamycin, doxy, etc in combination can be effective. Our experience is that they may be beneficial, but not necessarily curative, and the risk/benefit of using aminoglycosides like Gent need to be evaluated.
"Bartonella species appear to be susceptible to many antimicrobials, including penicillin, cephalosporins, fluoroquinolones, macrolides and aminoglycosides, but the correlation between in vivo and in vitro is lacking [17]. Gentamicin is the aminoglycoside that appears to be most studied [18]. There appear to be limited or no prospective studies to support treatment guidelines for endocarditis, and most recommendations are largely based on retrospective, observational data. Many experts recommend dual therapy for effective treatment, at least in the initial 2 weeks [18]. The AHA (2005 edition) recommends using doxycycline for 6 weeks after valve surgery or 12 weeks total if the valve is retained and gentamicin for at least 14 days. Alternatives to doxycycline are macrolides with recommendation for 12 weeks minimum with valve surgery and 6 months without surgery. Valve replacement seems to be central to appropriate therapy, having occurred in 80% of past cases [17]. If gentamicin cannot be used, notably in settings where renal function is a concern, the alternative is rifampin for at least 14 days. Gentamicin is chosen because aminoglycosides are bactericidal, and doxycycline has been shown to penetrate erythrocytes. The combination works well to eradicate the bacteria in different niches within the host [18], [19]. In a retrospective study of 101 patients, at least 14 days of aminoglycosides (in combination with another antimicrobial) demonstrated higher rates of recovery as compared to non-aminoglycoside monotherapy [20]. The question remains whether bactericidal activity is required for clearance of the organism. Some data shows Bartonella residing within erythrocytes may afford protection from gentamicin, hence the recommendation to use more than one agent [19]. Interestingly, there is in vitro data to support the use of azithromycin/ciprofloxacin and rifampin/ciprofloxacin combinations to completely eradicate biofilms after 6 days and kill stationary phase Bartonella after day 1 of exposure [21]. The total duration of antimicrobial treatment is not clearly defined, leaving room for future guidelines to assist with clarification."
From my perspective, the most important studies going forward to help LD patients involve treatment of resistant co-infections like babesia and bartonella, along with identification of new persister drugs for borrelia. Santa, please put that on the wish list for LD patients across the globe.
https://www.sciencedirect.com/science/article/pii/S221425092100322X
