Studies on the Interaction Between Serum Bactericidal Activity and Antibiotics in vitro

Chemotherapy ◽  
1970 ◽  
Vol 15 (2) ◽  
pp. 70-83 ◽  
Author(s):  
W.H. Traub ◽  
J.C. Sherris
1996 ◽  
Vol 40 (3) ◽  
pp. 776-779 ◽  
Author(s):  
M Trautmann ◽  
M Ruhnke ◽  
K Borner ◽  
J Wagner ◽  
P Koeppe

Sparfloxacin, a new fluorinated quinolone, exhibits higher in vitro activity against pneumococci than do ciprofloxacin and ofloxacin. Since up to 30% of cases of pneumococcal pneumonia are associated with bacteremia, and since an increasing percentage of pneumococci are resistant against penicillin, we studied the serum bactericidal activity of sparfloxacin against pneumococci in eight healthy, middle-aged volunteers. Pharmacokinetics in serum and urine after a 400-mg oral dose of sparfloxacin were comparable to those described by other authors. Inhibitory and bactericidal activities in serum were measured for four pneumococcal isolates representing penicillin-susceptible (one isolate), intermediately resistant (two isolates), and highly resistant (one isolate) strains. Geometric mean inhibitory titers ranged between 1:2.4 and 1:6.3 and bactericidal titers ranged between 1:1.3 and 1:3.6 during a time period of 1 to 6 h after drug intake. Although such titers were not sufficient to predict a clinical response based on previous pharmacodynamic studies using quinolone antibiotics, data obtained with volunteers may only partially reflect the clinical situation in which a rise of humoral antibodies directed against pneumococcal antigens may help to reinforce the bactericidal action of the antibiotic.


1994 ◽  
Vol 33 (1) ◽  
pp. 91-101 ◽  
Author(s):  
L. Aguilar ◽  
C. Esteban ◽  
J. Frias ◽  
I. Pérez-Balcabao ◽  
A. J. Carcas ◽  
...  

2004 ◽  
Vol 72 (10) ◽  
pp. 5903-5909 ◽  
Author(s):  
Jo Anne Welsch ◽  
Dan Granoff

ABSTRACT The hallmark of immunity to meningococcal disease is a bactericidal titer in serum of ≥1:4 measured with human complement, but this threshold titer may underestimate the extent of protection. We used the infant rat model of meningococcal bacteremia to measure group C passive protective activity in serum samples from 91 unimmunized adults living in California. A total of 35 sera (38.5%) had passive protective activity. Sera with complement-mediated bactericidal titers of ≥1:4 were 3.4-fold more likely to confer protection (89%) than nonbactericidal sera (26%; P < 0.0001). Thus, bactericidal titers of ≥1:4 are a marker of protection, but this threshold lacks sensitivity for predicting protective activity. We investigated the 73 sera with bactericidal titers of <1:4 to determine the basis of protective activity. The 19 sera with protective activity had a higher geometric mean group C anticapsular antibody concentration (0.72 μg/ml) than the 54 sera that lacked protective activity (0.16 μg/ml; P < 0.001). Thus, protective activity in the absence of bactericidal activity was associated with higher concentrations of anticapsular antibodies, but not all sera with anticapsular antibodies conferred protection. Of 18 nonbactericidal sera with anticapsular antibody concentrations between 0.31 and 0.99 μg/ml, the 11 sera that conferred protection had a higher mean antibody avidity constant (21.9 nM−1) than the 7 nonprotective sera (14.6 nM−1; P < 0.03). Thus, in sera with titers of <1:4, protective activity is associated with higher-avidity group C anticapsular antibodies, which are present in concentrations insufficient to elicit complement-mediated bacteriolysis in vitro but sufficient to confer protection in an in vivo bacteremia model.


2021 ◽  
Vol 22 (5) ◽  
pp. 2530
Author(s):  
Bijean D. Ford ◽  
Diego Moncada Giraldo ◽  
Camilla Margaroli ◽  
Vincent D. Giacalone ◽  
Milton R. Brown ◽  
...  

Cystic fibrosis (CF) lung disease is dominated by the recruitment of myeloid cells (neutrophils and monocytes) from the blood which fail to clear the lung of colonizing microbes. In prior in vitro studies, we showed that blood neutrophils migrated through the well-differentiated lung epithelium into the CF airway fluid supernatant (ASN) mimic the dysfunction of CF airway neutrophils in vivo, including decreased bactericidal activity despite an increased metabolism. Here, we hypothesized that, in a similar manner to neutrophils, blood monocytes undergo significant adaptations upon recruitment to CFASN. To test this hypothesis, primary human blood monocytes were transmigrated in our in vitro model into the ASN from healthy control (HC) or CF subjects to mimic in vivo recruitment to normal or CF airways, respectively. Surface phenotype, metabolic and bacterial killing activities, and transcriptomic profile by RNA sequencing were quantified post-transmigration. Unlike neutrophils, monocytes were not metabolically activated, nor did they show broad differences in activation and scavenger receptor expression upon recruitment to the CFASN compared to HCASN. However, monocytes recruited to CFASN showed decreased bactericidal activity. RNASeq analysis showed strong effects of transmigration on monocyte RNA profile, with differences between CFASN and HCASN conditions, notably in immune signaling, including lower expression in the former of the antimicrobial factor ISG15, defensin-like chemokine CXCL11, and nitric oxide-producing enzyme NOS3. While monocytes undergo qualitatively different adaptations from those seen in neutrophils upon recruitment to the CF airway microenvironment, their bactericidal activity is also dysregulated, which could explain why they also fail to protect CF airways from infection.


1993 ◽  
Vol 32 (2) ◽  
pp. 295-300 ◽  
Author(s):  
Franco Maggiolo ◽  
Alberto Taras ◽  
Stefano Frontespezi ◽  
Francesco Bottari ◽  
Maria Cristina Legnani ◽  
...  

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