Background
Methods
Study setting and patients
Laboratory setting and samples
Blood and heart valve cultures
Molecular methods
Ethics
Data analysis
Results
Patient characteristics
Demographics | Male (%) | 52 (76.5 %) |
Age (years) | 53.0 +/− 14.4 | |
Medical history | Prosthetic valve | 23 (33.8 %) |
Previous endocarditis | 4 (6.0 %) | |
Intravenous drug user | 3 (4.4 %) | |
Laboratory data | White Blood Cell count (×109/L) | 13.8 +/− 6.4 |
Peak ESR (mm/h) | 58.5 +/− 31.7 | |
Peak CRP (mg/L) | 118 +/− 94 | |
Transthoracic Echo Performed | 53 (77.9 %) | |
Trans-esophageal Echo Performed | 63 (92.6 %) | |
Culture data | Mean sets of Blood Cultures | 3.7 +/− 2.8 |
Any positive blood culture | 45 (66.2 %) | |
Percentage of positive blood cultures | 32.1 % | |
Mean time from last positive blood culture until surgery (days) | 15.4 +/− 24.7 |
Blood and heart valve culture
Molecular testing of heart valve tissue
Duke’s criteria | Cardiac tissue | Tissue gram stain | Tissue culture | Blood culture | Fast DPO PCR | Bacterial 16S sequencing Identification | Diagnostic impact |
---|---|---|---|---|---|---|---|
Definite | MV | GPC | No growth | No growth | Positive |
Staphylococcus lugdenensis
| New |
Definite | MV | Negative | No growth | No Growth | Positive |
Streptococcus dysgalactiae subsp. equisimilis
| New |
Definite | PAV | GPB | Cons; broth only | No growth | Positive |
P. acnes
| New |
Definite | MV | GPC | S. Mitis | No growth | Positive |
Streptococcus sanguinis
| Change |
Definite | MV papillary leaflet | Negative |
S. bovis group |
S. salivarius
| Positive |
S. gallolyticus subsp. pasteurianis
| Change |
Definite | AV | GPC | No growth |
S. bovis
| Positive |
S. gallolyticus subsp. pasteurianis
| Change |
Definite | MV Vegetation | Negative | No growth |
S. mitis
| Positive |
S. oralis/sanguinis
| Change |
Definite | AV | Negative | No growth |
S. salivarius
| Positive |
S. mitis group (S. cristatus/oralis/mitis) | Change |
Definite | MV | Negative | No growth |
S. salivarius
| Positive |
S. mitis group (S. cristatus/oralis/infantis) | Change |
Definite | AV vegetation | Negative |
S. bovis group |
S. bovis
| Positive |
S. gallolyticus subsp. gallolyticus
| Change |
Definite | AV vegetation | Negative | No growth | GGS | Positive |
S. dysgalactiae subsp. equisimilis
| Change |
Definite | PAV | Negative |
E. faecalis/CONS; broth only |
S. agalactiae
| Positive |
S. agalactiae
| Change |
Definite | AV vegetation | Negative | No growth |
S. mitis
| Positive |
S. sanguinis
| Change |
Definite | PMV | GPC |
S. mitis group | Group C Strep | Positive |
S. dysgalactiae subsp. equisimilis
| Change |
Definite | AV | GPC |
S. mitis group |
S. mitis
| Positive |
S. sanguinis
| Change |
Definite | PAV | Negative | No growth | CoNS | Positive |
E. faecalis
| Change |
Definite | MV | Negative | CoNS broth only | CoNS | Positive |
S. epidermidis
| Change |
Definite | MV Vegetation | Mixed GPC | No growth |
S. mitis
| Positive |
S. mitis
| None |
Definite | MV | Negative |
S. agalactiae; broth only |
S. agalactiae
| Positive |
S. agalactiae
| None |
Definite | AV abscess | Negative | No growth |
S. mitis
| Positive |
S. mitis group (mitis/tigurinus) | None |
Definite | AV abscess | Negative |
Enterococcus faecalis; broth only |
E. faecalis
| Positive |
E. faecalis
| None |
Definite | MV | Negative | No growth |
Haemophilus parainfluenzae
| Positive |
H. parainfluenzae
| None |
Definite | AV | Negative | No growth |
Streptococcus pneumoniae
| Positive |
S. pneumoniae
| None |
Definite | AV Vegetation | Positive |
E. faecalis
|
E. faecalis
| Positive |
E. faecalis
| None |
Definite | MV | GPC | No growth |
S. mitis
| Positive |
S. mitis
| None |
Definite | AV | Negative |
E. faecalis
|
E. faecalis
| Positive |
E. faecalis
| None |
Definite | AV | Negative | No growth |
E. faecalis
| Positive |
E. faecalis
| None |
Definite | AV | Negative | No growth |
E. faecalis
| Positive |
E. faecalis
| None |
Definite | Aortic lesion | Negative | No growth |
Granulicatella adiacens
| Positive |
G. adiacens
| None |
Definite | AV | GPC | No growth |
E. faecalis
| Positive |
E. faecalis
| None |
Definite | AV | Negative |
S. lugdenensis
|
S. lugdenensis
| Positive |
S. lugdenensis
| None |
Definite | AV | GPC | No growth |
S. mutans
| Positive |
S. mutans
| None |
Definite | Aortic annulus | Negative | No growth |
S. mitis
| Positive |
S. mitis
| None |
Definite | AV | Negative |
Cardiobacterium hominis
|
C. hominis
| Positive |
C. hominis
| None |
Definite | AV leaflet | Negative | No growth |
S. agalactiae
| Positive |
S. agalactiae
| None |
Definite | MV | Negative |
S. lugdenensis
|
S. lugdenensis
| Positive |
S. lugdenensis
| None |
Definite | AV leaflet | Negative |
E. faecalis
|
E. faecalis
| Positive |
E. faecalis
| None |
Definite | MV vegetation | Negative |
S. lugdenensis; broth only |
S. lugdenensis
| Positive |
S. lugdenensis
| None |
Definite | AV; left atrial lesion | Negative |
S. aureus; broth only |
S. aureus
| Positive |
S. aureus
| None |
Definite | AV | Negative | No growth |
S. mitis
| Positive |
S. mitis/sanguinis
| None |
Definite | PAV | Negative | No growth |
S. salivarius
| Positive |
S. salivarius
| None |
Definite | AV | Negative |
E. coli
| No growth | Positive |
E. coli
| None |
Definite | MV vegetation | GPB |
H. parainfluenzae
|
H. parainfluenzae
| Positive |
H. parainfluenzae
| None |
Definite | MV | Negative | CoNS; broth only | No growth | Negative | Not Done | None |
Definite | MV | Negative | No growth |
E. faecalis
| Positive |
E. faecalis
| None |
Definite | Aorta | Negative | No Growth |
E. faecalis
| Positive |
E. faecalis
| None |
Definite | AV | Negative | No Growth |
S. aureus
| Negative | Not done | None |
Definite | AV | Negative | No Growth |
S. aureus
| Positive | Mixed | None |
Definite | AV vegetation | Negative |
S. bovis
|
S. bovis
| Positive |
S. bovis
| None |
Definite | AV | Positive |
S. aureus
|
S. aureus
| Negative | Negative | None |
Possible | PAV | Negative | No growth | No Growth | Positive |
Acinetobacter junii
| New |
Possible | AV | Negative | No Growth | No Growth | Positive |
Delftia tsuruhatensis
| New |
Possible | AV | Negative | No Growth | No Growth | Positive |
S. infantis
| New |
Possible | AV | Negative | No growth | No growth | Negative | Negative | None |
Possible | AV | Negative | No Growth | No Growth | Negative | Negative | None |
Possible | PAV | Negative | No Growth | No Growth | Negative | Negative | None |
Possible | AV | Negative | No Growth | No Growth | Negative | Negative | None |
Possible | AV | Negative | No Growth | No Growth | Negative | Negative | None |
Negative | AV | Negative | No Growth | No Growth | Positive |
E. faecalis
| New |
Negative | MV | Negative | No Growth | No Growth | Negative | Negative | None |
Negative | MV | Negative | No Growth | No Growth | Negative | Negative | None |
Negative | PMV | Negative | No Growth | No Growth | Negative | Negative | None |
Negative | AV | Negative | No Growth | No Growth | Negative | Negative | None |
Negative | AV | Negative | No Growth | No Growth | Negative | Negative | None |
Negative | AV vegetation | Negative | No Growth | No Growth | Positive | Mixed | None |
Negative | MV thrombus | Negative | No Growth | No Growth | Negative | Negative | None |
Negative | MV | Negative | No Growth | No Growth | Negative | Negative | None |
Negative | AV | Negative | No Growth | No Growth | Positive | Mixed | None |
Method | Sensitivity | Specificity | PPV | NPV | Diagnostic efficiency |
---|---|---|---|---|---|
Gram Stain of Heart Valve Tissue | 26.0 % (15.1–40.6) | 100 % (78.1–100.0) | 100 % (71.7–100.0) | 32.7 % (21.0–46.8) | 45.6 % (33.8–57.4) |
Heart Valve Tissue Culture | 46 % (33.0–59.6) | 100.0 % (83.1–100.0) | 100.0 % (83.1–100.0) | 41.3 % (27.0–56.7) | 60.2 % (50.8–68.0) |
16S Broad Range PCR/Sequencing | 92.0 % (84.6–96.5) | 77.8 % (57.4–90.4) | 92.0 % (84.6–96.5) | 77.8 % (57.4–90.4) | 88.2 % (77.4–94.9) |
Effect of peri-operative antibiotic treatment
Literature review
Study (Reference) | Location | Median duration of pre-operative antibiotic treatment (days) | Cases/Controlsa
| Cases with positive pre-operative blood culture(s) | Nucleotide position of primers in E. coli 16S rRNA gene | Agreement of HV culture and 16s PCR | HV culture sensitivity/specificity | Sensitivity | Specificity | PPV | NPV |
---|---|---|---|---|---|---|---|---|---|---|---|
1 (Goldenberger, [8]) | Switzerland | NR b
| 18 | 14/18 (77.8 %) | 8-806 | 2/18 (11.1 %) | 11.1/100 % | 93.3 % | 66.7 % | 93.3 % | 66.7 % |
2 (Gauduchon, [13]) | France | 31.5 (range, 8 to 150) | 29/23 c
| 21/29 (72.4 %) | 911-930 and 1390-1371 | 27/29 (93.1 %) c
| NR | ND | ND | ND | ND |
3 (Lang, [19]) | UK | NR d
| 28/61 | 20/28 (71.4 %) | 1522-1540 and 1170-1189 | 14/20 (70 %) | NR | ND | ND | ND | ND |
4 (Breitkopf, [23]) | Germany | NR | 51/16 | 7/21 (33.3 %) | 8-27 and 907-926 | None | 7.8/93.7 % | 41.2 % | 100 % | 100 % | 34.8 % |
5 (Greub, [15]) | France | NR | 127/118 | 57/127 (44.9 %) | 536-1050 | 14/68 (20.6 %) | 13/98 % | 61 % | 100 % | 100 % | 74 %% |
6 (Rovery, [24]) | France | 19.5 (range, 1–150) | 147 | NR | 536-1050 | 64/95 (67 %) e
| NR | ND | ND | ND | ND |
7 (Kotilainen, [18]) | Finland | 19.6 (range 1–58d) | 28/18 | 20/28 (71.4 %) | 1054-1077 and 1950-1926 | 18/25 (72 %) | 13.1/100 % | 43.1 % | 100 % | 100 % | 58.1 % |
8 (Marin, [9]) | Spain | 10 (range, 1–25) | 35/120 | 31/35 (88.6 %) | 783-806 and 1389-1370 | 16/35 (45.7 %) | 24.3/56.4 % | 96 % | 95.3 % | 98.4 % | 88.5 % |
9 (Volstedlund, [25]) | Denmark | 19.3 (range, 0–90) | 57/10 | 50/57 (87.7 %) | 341-534 | 19/57 (33.3 %) | 26/62 % | 72 % | 100 % | 100 % | 62 % |
10 (Fournier, [30]) g
| France | NR | 549/191/19 | All patients had negative blood culture | Same as study (2) 536F and RP2 | 45.6 % | 45.7 %/NR | 69.2 % | ND | ND | ND |
11 (Miyazato, 2011) | Japan | 19 | 15/19 (79 %) | 8UA and 1485B | None: 79 % had a positive Gram stain | None were positive | 100 % | 100 % | 79 % | 100 % | |
12 (Vondracek, [27]) | Sweden | NR | 57/61 | 48/57 (84 %) | 334-939 | 20/57 (35.1 %) | 23/87 % | 77 % | 100 % | 100 % | 87 % |
13 (Boussier, [28]) f
| France | NR | 31 | 23/31 (74.2 %) | Same as (2) and 8-27 and 1510-1492 | 5/31 (16.1 %) | 32.3/100 % | 78 % | 100 % | 100 % | 61.5 % |
14 (Kemp, [17]) | Denmark | NR | 56/36 | 36/56 (64.3 %) | 8-534 | 7/42 (16.7 %) | 16.7/100 % | 88 % | 61.5 % | 88 % | 57.1 % |
15 (Sadaka, [29]) g
| Egypt | NR | 19 | All blood cultures were negative | 1522-1540 and 1170-1189 | 5/6 (83.3 %) | 62.5 %/NR | ND | ND | ND | ND |
16 (Harris, [16]) | Ireland, UK | NR | 47 | 35/47 (74.5 %) | 16S Fa, 16S Fb and 16SR (320 bp) | 29/47 (61.7 %) | NR | 67 % | 91 % | 96 % | 46 % |
17 (Leli, [31])h
| Italy | NR | 20 | NR | Septifast (Roche) | 3/19 (15.8 %) | 15.8/100 % | 95 % | 100 % | 100 % | 83.3 % |
18 (Marsch, [32]) i
| Germany | NR | 46 | NR | UMD™, Molzym | 27/46 (56.7 %) | 32.1/100 % | 61 % | ND | ND | ND |