Quantitation of bacteria in bone marrow from patients with typhoid fever: Relationship between counts and clinical features

Enteric fever is the only bacterial infection of humans for which bone marr ow examination is routinely recommended. A prospective study of the concent rations of bacteria in the bone marrow and their relationship to clinical f eatures was conducted with 120 Vietnamese patients with suspected enteric f ever, of whom 89 had confirmed typhoid fever, Ninety-three percent of the S almonella enterica serovar Typhi samples isolated were resistant to ampicil lin, chloramphenicol, and co-trimoxazole. For 81 patients with uncomplicate d typhoid and satisfactory bone marrow aspirates, the number of serovar Typ hi CFU in bone marrow aspirates was a median value of 9 (interquartile rang e [IQR], 1 to 85; range, 0.1 to 1,580) compared to 0.3 (IQR, 0.1 to 10; ran ge, 0.1 to 399) CFU/ml in simultaneously sampled blood. The ratio of indivi dual blood counts to bone marrow counts was 10 (IQR, 2.3 to 97.5), The numb er of bacteria in blood but not bone marrow was correlated inversely with t he duration of preceding fever. Thus, with increasing duration of illness t he ratio of bone marrow-to-blood bacterial concentrations increased; the me dian ratio was 4.8 (IQR, 1 to 27.5) during the first week compared with 158 (IQR, (60 to 397) during the third week. After lysing the host cells, the median ratio of viable bone marrow to blood increased, I reflecting the hig her concentration of intracellular serovar Typhi in the bone marrow. Effect ive antibiotic pretreatment had a significantly greater effect in reducing blood counts compared to bone marrow counts (P < 0.001). Thus, bacteria in the bone marrow of typhoid patients are less affected by antibiotic treatme nt than bacteria in the blood. The numbers of bacteria in bone marrow corre lated negatively with the white blood cell (R = -0.3, P = 0.006) and platel et counts (R = -0.32, P = 0.01) and positively with fever clearance time af ter treatment (R = 0.4, P < 0.001), The bacterial load in bone marrow there fore may reflect the clinical course of the infection, and high levels may suppress neutrophil proliferation.