Table 1. Features of Studies Demonstrating Unexpected Positive Blood Cultures for Lyme Borrelia.

Reference	Year	Material Cultured	Culture Method	Findings	Why Findings Unexpected	Aspects of Study that Raise Concerns on Validity	Comment
Phillips et al [13]	1998	Plasma	“MPM”medium used	43 (91%) of 47 patients with “chronic Lyme disease” had a positive blood culture. Positive blood cultures were confirmed using both polyclonal and monoclonal antibody to Lyme borrelia, as well as by both electron microscopy and immunoelectron microscopy.	All patients had previously been treated with antibiotics and most (>90%) were seronegative for antibody to Lyme borrelia by two-tier testing. Indeed, all patients had previously received ≥ 6 weeks of IV ceftriaxone or another third generation cephalosporin. The 91% rate of positive blood cultures far exceeded the rate reported for untreated patients with early Lyme disease [10,11].	Used an unconventional culture medium that included Detroit tap water. Study results could not be replicated by other investigators. The novel culture medium used was shown to be bactericidal against strains of Borrelia burgdorferi sensu stricto inoculated into it [15,16].	Study did not present evidence that patients ever actually had Lyme disease.
Sapi et al [12]	2013	Serum	Modified BSK-H medium with rifampin using a 2-stage culture method that included collagen-coated slides.	68 (94%) of 72 patients had a positive blood culture. Positive blood cultures were confirmed using both polyclonal and monoclonal antibody to Lyme borrelia, as well as by PCR and by sequencing of PCR products.	The 94% rate of positive blood cultures far exceeded that reported for untreated patients with early Lyme disease [10,11].	Genetic sequencing data suggested that most of the isolates were not Borrelia burgdorferi sensu stricto, consistent with laboratory contamination. No data provided on the patients' clinical manifestations.	No corroboration of blood culture success by an independent laboratory. Unclear how many of the patients had previously been treated for Lyme disease, but some, if not all, may have been treated previously, although not within the prior four weeks before the blood sample was collected.
Rudenko et al [14]	2016	Culture of plasma or serum with three positive cultures from plasma.	Modified Kelly-Pettenkofer (MKP) medium and BSK-H medium; unclear how long after blood collection it was cultured, but was at least 5 days and possibly as long as 48 days.	At least 3 (13%) of 24 patients with non-specific symptoms had a positive blood culture for borrelia, two for Borrelia burgdorferi sensu stricto and one for a Borrelia bissettii-like strain. Positive blood cultures were confirmed using transmission electron microscopy, scanning electron microscopy, PCR, sequencing of PCR products, sequence analysis and multilocus sequence analysis.	Lyme disease not endemic in the States in which the patients resided. Borrelia bissettii not established to cause human infection in the United States.	No confirmatory testing of blood specimens by PCR before culture and no repeat blood cultures performed in patients with positive cultures. All patients had been previously treated for Lyme disease before cultures done. One patient had doxycycline still present in blood at time of culture and after completion of a 40 day treatment course. Doxycycline sensitivity of borrelial isolates not evaluated.	Investigators had previously isolated many strains of both Borrelia burgdorferi sensu stricto and Borrelia bissettii from non-human sources, raising concern that there could have been laboratory contamination. Apparently isolates could not be sub-cultured successfully in BSK-H medium.

PCR= Polymerase chain reaction