Table 1.
Clinical features of patients infected with Bartonella
| Case # | Reference interval | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 |
|---|---|---|---|---|---|---|---|---|---|---|
| Age (years), gender | – | 31, female | 59, male | 53, male | 45, male | 61, male | 19, male | 20, male | 37, male | 60, female |
| Associated conditions | – | Trisomy 21, pulmonary atresia with RV-PA catheter and LVOT obstruction. | History of resolved acute renal failure | History of aortic dissection with mechanical aortic valve repair | HIV (CD4 247), ESRD on peritoneal dialysis | Polycystic kidney disease requiring kidney transplant, complicated by cellular rejection; on immunosuppressive therapy | TOF s/p palliation with biventricular repair, RV-PA conduit replacement, and placement of a Melody valve | TOF and pulmonary atresia s/p BTT shunt, RV to PA conduit placement 4 years prior | Former PWID | None |
| Associated exposures | – | Dog and cat at home | Rancher of exotic animals | Work cleaning out horse stables | None found | Two cats at home | Dog and hamster at home | Two dogs at home | Unknown | None found |
| Initial suspected diagnosis | – | Bacterial, viral, or tickborne infection vs vasculitis | Malignancy, auto-immune disorder, Brucella, Bartonella | Gram-positive infective endocarditis, Brucella, Bartonella, or Coxiella | Coagulase-negative staphylococcal bacteremia | Viral infection | Brucella, Bartonella or Coxiella | Bacterial infective endocarditis | Bacterial infective endocarditis | Urosepsis |
| Fever >100.4°F | – | No | No | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
| Shock | – | Yes | No | No | Yes | No | Yes | No | Yes | No |
| Initial labs | ||||||||||
| WBC (k/µL) | 4–10 | 5.3 | 4.8 | 3.1 | 8.2 | 4.43 | 6.1 | 6.9 | 4.6 | 7.5 |
| Hemoglobin (g/dL) | 12–15 | 12.3 | 6.0 | 6.0 | 5.0 | 13.8 | 7.8 | 8.4 | 9.0 | 12.0 |
| Platelet count (k/µL) | 150–450 | 22.4 | 115 | 134 | 142 | 155 | 116 | 204 | 101 | 281 |
| BUN (mg/dL) | 7–19 | 19 | 68 | 18 | 54 | 20 | 42 | 19 | 73 | 11 |
| Creatinine (mg/dL) | 0.6–1.3 | 3.3 | 5.1 | 0.8 | 15.2 | 1.6 | 3.1 | 1 | 7.9 | 0.8 |
| C-Reactive protein (mg/Dl) | 1 | Not done | 5.01 | Not done | Not done | 3.01 | 2.8 | 6.1 | Not done | 15.9 |
| Procalcitonin (ng/mL) | <0.05 | 1.64 | 0.75 | Not done | 2.79 | Not done | 0.49 | 0.46 | 16.68 | Not done |
| Lactate dehydrogenase (U/L) | 115–220 | 448 | 269 | 277 | Not done | Not done | 247 | 218 | Not done | 318 |
| Complement levels (mg/dL) | C3: 82-193 C4: 15-57 |
C3: 28 C4: 6 |
C3: 80 C4:13 |
Not done | Not done | Not done | Not done | Not done | C3: 39 C4: 6 |
Not done |
| PR3-ANCA (AI) | <1.0 | 2.6 | 6.1 | <1.0 | Not done | Not done | Not done | Not done | Not done | Not done |
| Fibrinogen (mg/dL) | 225–434 | 79 | 186 | Not done | Not done | Not done | 208 | Not done | 202 | 550 |
| Urinalysis | ||||||||||
| Blood | Negative | Large | Large | Moderate | Large | Negative | Large | Large | Large | Negative |
| RBC (cells/HPF) | 0–5 | >182 | 237 | 1 | 600 | 3 | 51–100 | 21–50 | >182 | 3 |
| WBC (cells/HPF) | 0–5 | 7 | 5 | 1 | 2 | 2 | 5–10 | 5–10 | 0 | 24 |
| Protein (mg/dL) | Negative | 50 | 30 | Negative | 100 | +1 (semi-quantitative) | +2 (semi-quantitative) | +3 (semi-quantitative) | ≥300 | 20 |
| Microbiology | ||||||||||
| Bartonella cultures | No growth | No growth × 4 blood cultures | Not done | Not done | Not done | Not done | Not done | Not done | Not done | Not done |
| Bartonella serology | IgM: 1:20 | B henselae: | B henselae: | B henselae: | B henselae: | B henselae: | B henselae: | B henselae: | B henselae: | B henselae: |
| IgG: 1:64 | IgG: ≥1:1024 | IgG ≥1:1024 | IgG ≥1:1024 | IgG ≥1:1024 | IgG ≥1:2560 | IgG ≥1:1024 | IgG ≥1:1024 | IgG ≥1:1024 | IgG ≥1:1024 | |
| IgM negative | IgM negative | IgM negative | IgM negative | IgM negative | IgM ≥ 1:256 | IgM ≥ 1:256 | IgM negative | IgM 1:160 | ||
| B quintana: | B quintana: | B quintana: | B quintana: | B quintana: | B quintana: | B quintana: | B quintana: | B quintana: | ||
| IgG negative | IgG ≥1:1024 | IgG negative | IgG negative | IgG ≥1:1280 | IgG ≥1:512 | IgG negative | IgG 1:64 | IgG negative | ||
| IgM negative | IgM negative | IgM negative | IgM negative | IgM negative | IgM negative | IgM ≥1:256 | IgM negative | IgM 1:20 | ||
| Bartonella PCR | 250 copies/ml | Not done | Negative for B henselae, B quintana | Not done | Not done | Not done | Not done | Not done | Not done | Negative for B henselae, B quintana |
| mcfDNA Bartonella concentration and species | <10 MPM | Positivea B henselae | 26,651 B vinsonii | Positivea B henselae | 302 B henselae | Positivea B henselae | 33,034 B henselae | 33, 430 B henselae | >316,000 B henselae | 3,032 B henselae |
| Other mcfDNA NGS | – | None | None | None | EBV (557 MPM)b | Torque teno virusa, b | None | None | EBV (457 MPM)b | None |
| mcfDNA NGS clinical TAT (days) | – | 3 | 2 | 2 | 2 | 5 | 7 | 2 | 2 | 3 |
| mcfDNA NGS laboratory TAT (days) | – | 1 | 1 | 1 | 1 | 1 | 3 | 1 | 1 | 1 |
| Serology/PCR clinical TAT | – | 6 (serology) | 5 (serology) 2 (valve tissue PCR) |
4 (serology) | 4 (serology) | 4 (serology) | 3 (serology) | 4 (serology) | 4 (serology) | 8 (serology) 4 (whole blood PCR) |
| Serology/PCR laboratory TAT | – | 2 (serology) | 2 (serology) 1 (valve tissue PCR) |
2 (serology) | 2 (serology) | 4 (serology) | 1 (serology) | 4 (serology) | 2 (serology) | 8 (serology) 7 (whole blood PCR) |
| Imaging | ||||||||||
| Trans-thoracic echocardiogram | – | Probable cleft mitral valve, otherwise unremarkable. | Calcified mass fixed on the posterior mitral valve leaflet. | Normal prosthetic aortic valve appearance and function | Mild aortic valve cusp thickening | Not done | Pulmonary valve thickening concerning for vegetation | New echobright densities in proximal (RV-PA) conduit with limited valve leaflet visualization | Severely enlarged left ventricle and large aortic valve echo-densities, largest 1.6 x 0.6 cm | No significant valvular heart disease |
| Trans-esophageal echocardiogram | – | Not done | Globular calcified density in posterior leaflet causing severe mitral regurgitation | No evidence of vegetations or endocarditis. | Not done | Not done | Not done | Not done | Not done | Not done |
| Clinical impact | ||||||||||
| Modified Duke criteria | – | Possible | Definite | Definite | Rejected | Rejected | Definite | Definite | Definite | Rejected |
| Hospital stay (days) | – | 10, 16c | 25 | 21 | 9 | Not hospitalized | 42 | 6 | 46 | 16 |
| ICU admission | – | Yes | Yes | Yes | No | No | Yes | No | Yes | No |
| Death | – | Yes | No | No | No | No | No | No | No | No |
| First positive diagnostic result and days to result | – | mcfDNA NGS (4 days)d | mcfDNA NGS (7 days) | mcfDNA NGS (7 days) | mcfDNA NGS (8 days) | mcfDNA NGS (21 days) | Bartonella serology (3 days) | mcfDNA NGS (not hospitalized) | mcfDNA NGS (8 days) | mcfDNA NGS (5 days) |
Note. RV-PA: right ventricle-pulmonary artery; LVOT: left-ventricular outflow tract; PWID: person who injects drugs; ESRD: end-stage renal disease; TOF: tetralogy of Fallot; WBC: white blood cells; BUN: blood urea nitrogen; PR3-ANCA: proteinase 3-antineutrophil cytoplasmic antibodies; RBC: red blood cells; PCR: polymerase chain reaction; mcfDNA: microbial cell-free DNA; NGS: next-generation sequencing; MPM: molecules per microliter; TAT: turnaround time; ICU: intensive care unit; CMV: cytomegalovirus; EBV: Epstein-Barr virus; HHV: human herpesvirus; AFB: acid-fast bacillus; ANA: antinuclear antibody; ASO: antistreptolysin O; RF: rheumatoid factor; TPO: thyroid peroxidase; ANCA: antinuclear cytoplasmic antibody; TSH: thyroid-stimulating hormone.
a
Some patients seen in 2017 received an earlier version of mcfDNA NGS studies that did not quantify the MPM of mcfDNA. Instead, the samples were tested with a negative buffer control.
b
Epstein-Barr virus and torque teno virus were found in small concentrations in 2 patients, but were not considered clinically significant by treatment teams and may have been the result of mild viremia in the setting of a secondary source of critical illness.
c
The patient was discharged after 10 days and was later readmitted for 16 days resulting in death.
d
Tests for an organism not detectable by mcfDNA NGS assay.