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Biomedical subjects

R F Jacobs

Publications and source records attributed to R F Jacobs.

At least 127 records · Page 7Linked to original sources
PubMed1983

Intracellular penetration and antimicrobial activity of antibiotics.

Delayed response or recurrence of clinical infections may, in part, be due to the inability of certain antibiotics to penetrate human polymorphonuclear leukocytes (PMN) and exert intracellular antibacterial activity. We determined the penetration of PMN by certain hydrophilic and certain lipophilic antibiotics, and assessed their activity against intracellular Haemophilus influenzae, type b or Staphylococcus aureus. We found that penicillin G was excluded from human PMN while chloramphenicol was concentrated within these cells; chloramphenicol killed significantly more intracellular H. influenzae than did penicillin or ampicillin. Clindamycin and trimethoprim penetrated into normal and chronic granulomatous disease (CGD) PMN equally and were at least transiently concentrated in the cells. Clindamycin and the combinations trimethoprim/sulphamethoxazole and trimethoprim/rifampicin were most effective in killing intracellular Staph. aureus in vitro; these antibiotics reduced the bacterial density in CGD PMN to values comparable to those in normal PMN. The mechanism by which clindamycin and rifampicin killed intracellular Staph. aureus appeared to be due to direct antimicrobial activity. Antibiotics that penetrate into phagocytes may be more effective in infections due to pathogens capable of intracellular survival.

Anti-Bacterial Agents↗
PubMed1983

Age-dependent effects of aminobutyryl muramyl dipeptide on alveolar macrophage function in infant and adult Macaca monkeys.

We compared the antimicrobial function of alveolar macrophages (AM) from adult and 3- to 5-wk-old infant primates (Macaca nemestrina) and the effects of the immunomodulator, aminobutyryl muramyl dipeptide (abu-MDP) on this function. Phagocytosis of Staphylococcus aureus (SA) and group B streptococcus (GBS) by adult and infant AM was comparable. Adult and infant AM killed SA equally within 15 min of incubation; however, after 45 min, with phagocytosis of additional bacteria, adult AM had greater bactericidal activity (p less than 0.01). The bactericidal activity of infant and adult AM against GBS was comparable after 45 min of incubation; infant AM had slightly but significantly greater bactericidal activity with short incubation (15 min; p less than 0.025). The bactericidal activity of abu-MDP-treated infant AM against SA (p less than 0.01) and GBS (p less than 0.05) was greater than that of untreated infant AM and untreated or abu-MDP-treated adult AM. The abu-MDP did not significantly (p greater than 0.2) enhance the antimicrobial activity of adult AM. Catalase, but not superoxide dismutase or mannitol, significantly (p less than 0.005) increased survival of GBS in infant AM; this effect was comparable in abu-MDP-treated and in untreated AM. The abu-MDP-treated infant, but not the adult AM, released more acid phosphatase when triggered by opsonized zymosan than did untreated AM, but superoxide anion release by infant or adult AM was not affected by incubation with abu-MDP.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Activity of antibiotics in chronic granulomatous disease leukocytes.

Patients with chronic granulomatous disease (CGD) have recurrent infections with catalase-producing organisms, particularly staphylococci, that survive within their leukocytes. To be most effective, antibiotics used to treat infections in CGD patients may need to kill both intracellular and extracellular organisms. We studied the ability of certain antibiotics to penetrate normal and CGD neutrophils and to kill intracellular staphylococci. Trimethoprim and clindamycin were concentrated in normal and in CGD neutrophils; maximum cellular-to-extracellular concentration ratios of clindamycin and of trimethoprim were approximately 30 and approximately 4, respectively. In contrast, penicillin was excluded from normal neutrophils. Clindamycin, trimethoprim/sulfamethoxazole, rifampin, and trimethoprim/rifampin significantly reduced the number of viable intracellular staphylococci in normal and CGD neutrophils. After 24 h of incubation in the presence of these antibiotics, the number of viable intracellular staphylococci in normal and CGD neutrophils was similar. In contrast, dicloxacillin, gentamicin, and cephalothin had no significant effect on the number of intracellular staphylococci in normal or CGD neutrophils.

Anti-Bacterial Agents↗
PubMed1983

Cellular immunotoxicity of amyl nitrite.

Functional deficits in lymphocyte interaction following occasional or chronic exposure to inhaled nitrites may be a potential contributing but not the etiologic factor in the acquired immunodeficiency syndrome (AIDS). We evaluated the effect of amyl nitrite vapors on mononuclear cell function and demonstrated functional deficits and structural alterations in these cells. In this closed, in vitro system, exposure of cells to amyl nitrite for up to 30 minutes did not effect cell viability. The functional deficits demonstrated were: inhibition of lymphocyte erythrocyte (E) rosette formation, a suppression of lymphocyte mitogen (phytohemagglutinin) and antigen (cytomegalovirus) transformation, a block in the S, G2 and M phases of cell cycling and diminished cell cytotoxicity to CMV infected cells. These effects on cellular function were demonstrated following 5, 10, and 15 minutes of amyl nitrite vapor exposure; some effect on all cellular functions was demonstrated at 5 minutes. The structural alterations seen on scanning and transmission electron micrographs were: reduction of filapodia, smoothing of the cell profile, cytoplasmic protrusions with pseudopod-like extensions, an increase in rough endoplasmic reticulum with swollen cisternae, alterations in size and distribution of golgi components and exocytotic vesicles in the outer membrane of the nuclear envelope. These vesicles and increased membrane proliferation suggests an effect on the membrane synthesis mechanism in these cells. These effects may be a potential factor in the alterations of phenotypic markers on T lymphocyte populations, as well as, a potential contributing factor in the functional deficit of mononuclear cells in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Apparent meningococcemia: clinical features of disease due to Haemophilus influenzae and Neisseria meningitidis.

To determine the etiology of apparent meningococcemia, all cases of sepsis with coagulopathy, purpura, and/or adrenal hemorrhage (Waterhouse-Friderichsen syndrome) with and without shock occurring over a 12-year period were reviewed. A total of 42 cases were identified; 30 cases were caused by Neisseria meningitidis and 12 cases were caused by Haemophilus influenzae. Compared with patients with disease caused by H influenzae, patients with meningococcal disease were older, more often male, more often contracted the disease in winter-spring, and had a longer duration of antecedent symptoms; however, none of these differences was statistically significant. All patients were febrile (greater than 38 degrees C) and appeared toxic. Similar proportions in each group had shock and disseminated intravascular coagulopathy at the time of admission. Ten of 12 patients with H influenzae infection compared with 15/30 (P less than .05) with meningococcal infection were lethargic or comatose at the time of admission. Nine of 12 patients with H influenzae infection died compared with 5/30 with meningococcal disease (P less than .005); the mean time from onset of symptoms to death with H influenzae infection (20.7 +/- 11.4 [SE] hours) was significantly shorter (P less than .05) than with meningococcal infection (120 +/- 74.4 hours). Children with clinical signs of sepsis and with purpura, petechiae, or coagulopathy may have N meningitidis or H influenzae as etiologic agents. Initial antibiotic therapy should be directed against these pathogens.

Age Factors↗
PubMed1982

Cellular uptake and intracellular activity of antibiotics against Haemophilus influenzae type b.

The ability of penicillins and chloramphenicol to enter human polymorphonuclear leukocytes (PMNLs) and their antibacterial activity against intracellular Haemophilus influenzae type b were studied. Penicillin was excluded whereas chloramphenicol was concentrated in PMNLs; chloramphenicol uptake was not dependent on PMNL energy and was not competitively inhibited by unlabeled drug. PMNLs that had phagocytized opsonized H. influenzae type b were examined after incubation for 24 hr. In the absences of antibiotics, intact intracellular H. influenzae type b organisms were observed in PMNLs by electron microscopy. These PMNLs contained 10(4.5) colony-forming units (cfu) of H. influenzae type b. Addition of penicillin or ampicillin at four, 20, or 40 times the minimal bactericidal concentration (MBC) decreased this density from 10(4.5) to 10(3.5) cfu. In contrast, addition of chloramphenicol at four times the MBC reduced the density to approximately 100 cfu; at 10 times the MBC it reduced the density to approximately 10 cfu. Thus, lipid-soluble antibiotics such as chloramphenicol are concentrated and are bioactive within PMNLs. Such antibiotics may have a significant advantage at the cellular level.

Adult↗
PubMed1982

Management of Pseudomonas osteochondritis complicating puncture wounds of the foot.

Pseudomonas osteochondritis following puncture wounds of the foot is described in 13 children. All children had received at least one oral antibiotic and local wound therapy before admission; none had improved on these modalities. Pseudomonas aeruginosa was isolated alone from seven patients and with one or more other organisms from six patients. Initial administration of parenteral antibiotics active against Pseudomonas for one to 14 days did not result in clinical improvement. Eradication of Pseudomonas osteochondritis occurred in each patient only after thorough surgical debridement and curettage of all infected tissue. Following thorough surgical debridement, anti-Pseudomonas antibiotic therapy was continued for five to 14 days (10.8 +/- 2.7 days). The successful treatment of Pseudomonas osteochondritis should include adequate surgical debridement of all infected tissue; following thorough debridement, only one to two weeks of anti-Pseudomonas antibiotic therapy appears to be necessary.

Adolescent↗
PubMed1982

Cellular antibiotic pharmacology.

Many perinatal pathogens are able to survive and in some cases replicate intracellularly. With the exception of viruses and toxoplasma, these pathogens principally infect phagocytic cells of the reticuloendothelial system. Such intracellular organisms, by evading the effects of antibiotics that act only extracellularly, may respond poorly to conventional therapy. Of currently available antibiotics, rifampin, chloramphenicol and trimethoprim are the most active intracellularly. Other antibiotics are either taken up by cells but appear to be inactive intracellularly (lincomycin) or are excluded from cells (penicillins, cephalosporins, aminoglycosides). The clinical role of antibiotics that are active intracellularly is not clear; anecdotal human experience and limited controlled animal experience suggests that they may be useful in the treatment of some infections. Because of the decreased microbicidal activity of newborn phagocytes, intracellular activity of antibiotics may be of greater importance than in older patients. Further study is needed to answer these questions. Methods of enhancing intracellular activity of antibiotics are available should this property prove to be desirable.

Anti-Bacterial Agents↗
PubMed1981

Detection of streptococcal antigen by counterimmunoelectrophoresis.

Rapid detection systems for identifying antibody or bacterial antigen have been used for two to three years. The analysis for the presence of bacterial antigen by counterimmunoelectrophoresis has been used in the detection of neonatal and pediatric infections. In the present report, the previous data concerning the detection of group B streptococcal antigen in cerebrospinal fluid, sera, and urine of infected newborns was reinforced. Counterimmunoelectrophoresis was also established as a method for detecting group B streptococcal antigen in amniotic fluid and group D streptococcal antigen in body fluids, and for verifying group A streptococcal antigen from 24-hour culture plates. This is a further extension of the use by the clinical laboratory of counterimmunoelectrophoresis in the detection of bacterial antigen.

Amniotic Fluid↗