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C C Patrick

Publications and source records attributed to C C Patrick.

At least 37 records · Page 2Linked to original sources
PubMed1995

Comparative virulence of Staphylococcus epidermidis isolates in a murine catheter model.

Among coagulase-negative staphylococci, Staphylococcus epidermidis is the species most commonly implicated in catheter-related infections. Whether some staphylococcal organisms are inherently more virulent than others, or whether their ability to infect relates more to the sheer numbers of organisms at the catheter site, remains unclear. We therefore compared eight S. epidermidis isolates and two other coagulase-negative staphylococci using a murine model that allowed us to quantify catheter colonization and abscess formation in the same animal. The organisms were isolated from different clinically relevant settings and were classified according to their slime phenotype. The ability to evoke abscesses or colonize catheters in half of the animals (ID50) was assessed. ID50 inoculum titers (log10 data +/- SD) ranged widely, from 8.5 +/- 0.3 to 10.2 +/- 0.2 for abscess formation (p < 0.005) and from 7.5 +/- 0.5 to 10.3 +/- 1.0 for catheter colonization (p < 0.005). ID50 values by statistical criteria suggested variability among organisms in the ability to induce abscess formation. High slime production correlated with both parameters, but not with the clinical source of the isolate. Our findings demonstrate impressive heterogeneity in the ability of a representative group of S. epidermidis isolates to colonize catheters and to evoke abscess formation and implicate slime productivity as a major virulence factor. The murine model used permitted simultaneous analysis of multiple factors involved in pathogenesis and should be useful in establishing the basis of S. epidermidis pathogenicity.

Abscess↗
PubMed1994

Pseudomonas aeruginosa bacteremia in immunocompromised children: analysis of factors associated with a poor outcome.

We identified 98 children and adolescents with cancer who were treated for Pseudomonas aeruginosa bacteremia over a 27-year period. The most common underlying disease was leukemia (lymphoblastic in 63 cases and myeloblastic in 17); in addition, 12 episodes were associated with solid tumors and 6 with other diagnoses. There were 29.5 episodes of P. aeruginosa bacteremia/1,000 cases of acute lymphoblastic leukemia, with a mortality of 27%, and 29.8 episodes/1,000 cases of acute myeloblastic leukemia, with a mortality of 24%; patients with solid tumors had an incidence of 5.0/1,000 cases and a mortality of 58% (P = .01 for mortality in leukemia vs. mortality in solid tumors, logistic regression analysis). Mortality was lower among children who developed bacteremia during remission therapy or induction therapy than among children who were being treated for relapse (P = .001). The majority (78%) of the 76 evaluated cases developed during periods when the absolute neutrophil count (ANC) was < 0.1 x 10(9)/L; mortality was higher among patients with such counts than among those with higher ANCs (36% vs. 14%, P = .04). Logistic regression analysis showed that perineal skin lesions were associated with higher mortality than were lesions at other sites of skin involvement (54% vs. 23%, P = .04).

Adolescent↗
PubMed1994

Monoclonal antibodies against a 97-kilodalton antigen from Aspergillus flavus.

We prepared a panel of five monoclonal antibodies (MAbs) directed against Aspergillus flavus that all reacted against one 97-kDa antigen by western blot (immunoblot). Flow cytometry demonstrated that these antibodies bound (in increasing degrees) to all morphologic stages of A. flavus growth: conidia, swollen conidia, and hyphae. Cross-reactivity among species was examined by enzyme-linked immunosorbent assay of fungal culture filtrates. Four MAbs reacted with 10 of 11 A. flavus isolates, and the fifth one reacted with 9 of them. One MAb also reacted with A. fumigatus, two reacted with A. niger, A. wentii, and A. nidulans, and all five reacted with A. ochraceus. None reacted with A. terreus, A. glaucus, A. versicolor, or a Penicillium species. Each MAb bound to A. flavus hyphae in formalin-fixed paraffin sections of a muscle biopsy from a confirmed human case of invasive aspergillosis. In summary, these MAbs identified a 97-kDa antigen found on A. flavus that is both surface bound and an exoantigen. Either the same or a cross-reacting antigen is present in A. fumigatus and other Aspergillus species.

Animals↗
PubMed1993

Variation in phenotypic expression of the Opa outer membrane protein and lipooligosaccharide of Neisseria meningitidis serogroup C causing periorbital cellulitis and bacteremia.

Expression of the Opa outer membrane protein varies widely among isolates of Neisseria meningitidis; the clinical significance of this variation is unclear. A sialic-acid acceptor is present in the lipooligosaccharide of some strains of Neisseria and has been shown to render Neisseria gonorrhoeae serum-resistant. We report the case of a patient who had an unusual clinical manifestation of infection due to N. meningitidis serogroup C, periorbital cellulitis with concomitant bacteremia. Clinical isolates from the blood and aspirate of the periorbital cellulitis were identical except for the phenotypic expression of the Opa outer membrane protein in the isolate from the periorbital cellulitis and in the lipooligosaccharide phenotype of the sialic-acid acceptor as defined by monoclonal antibodies. We discuss the laboratory and clinical implications of these findings.

Antigens, Bacterial↗
PubMed1993

Cunninghamella infections: review and report of two cases of Cunninghamella pneumonia in immunocompromised children.

Infections caused by Cunninghamella bertholletiae are being identified with increasing frequency in immunocompromised patients. We have treated two children with cancer for pulmonary infections caused by this rare fungus. Cunninghamella infection is found in a variety of populations of patients, including both children and adults undergoing chemotherapy. Clinical signs and symptoms are indistinguishable from those of other forms of zygomycosis. Outcome is poor: only three of 17 patients with such infection (including one of the two children described herein) have survived. Treatment involves aggressive surgical excision and administration of amphotericin B.

Child↗
PubMed1993

Typhlitis in children with cancer: a 30-year experience.

We identified 24 children treated for malignancies between 1962 and 1992 who had antemortem diagnoses of typhlitis that were confirmed on review. The study criteria specified the presence of fever, abdominal pain, and tenderness, with radiological evidence of right-sided colonic inflammation. Typhlitis was most frequent in patients treated for acute leukemias. Computed tomography and ultrasonography were more sensitive than plain radiography (false-negative rates, 15%, 23%, and 48%, respectively). The wider availability of these sensitive procedures and the increased intensity of chemotherapeutic regimens may account for a marked increase in the incidence of typhlitis over the past 5 years. Most patients responded to aggressive medical management, and typhlitis was fatal in only two cases (1 of 21 cases managed medically and 1 of 3 taken to surgery). Seven patients are alive > 1 year following the diagnosis. These findings contrast with prior descriptions of typhlitis as a preterminal event. Computed tomography and/or ultrasonography should be performed in all neutropenic patients with right-lower-quadrant signs to permit prompt diagnosis and treatment.

Adolescent↗
PubMed1993

Complications of bacteremia due to Stomatococcus mucilaginosus in neutropenic children.

Stomatococcus mucilaginosus, a normal inhabitant of the human oral cavity and upper respiratory tract, can cause fatal sepsis and meningitis in neutropenic patients. We identified eight cases of bacteremia due to S. mucilaginosus in children with cancer, of whom five developed complications despite receiving appropriate antibiotics. At the time cultures were positive, seven patients had profound neutropenia (< 100 neutrophils and band forms/mm3) and four had mucositis; five had central venous catheters. In two cases, there was unequivocal evidence of catheter-related sepsis. Bacteremia was eradicated in all patients within 48 hours after initiation of antibiotics. Despite prompt instigation of effective antibiotic therapy, the complication rates in this series were high: septic shock (50%), pneumonia (50%), dermatologic manifestations (38%), altered neurological status (25%), meningitis (13%), and adult respiratory distress syndrome (13%). No fatalities were attributable to S. mucilaginosus infection. These cases illustrate the virulence of S. mucilaginosus organisms in neutropenic children and suggest a substantial risk of sequelae even when adequate antibiotic therapy is given.

Adolescent↗
PubMed1993

Outer membrane protein binding sites of complement component 3 during opsonization of Haemophilus influenzae.

Complement component 3 (C3) binding to Haemophilus influenzae type b (Hib) is an important step in host defense against invasive disease, but the details of this process remain poorly understood. We have shown that the P1 and P2 outer membrane proteins (OMPs) serve as binding sites for C3 on serum-opsonized Hib. Whole-cell lysates of opsonized Hib were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the resolved proteins were transferred to nitrocellulose. Immunoblot analysis with monoclonal antibodies (MAbs) to the 49-kDa P1 and 39-kDa P2 OMPs demonstrated high-molecular-weight bands that were not present when the bacteria were opsonized with heat-inactivated or methylamine-treated serum. Immunoblot analysis with MAbs to the 98- or 16-kDa (P6) OMPs did not reveal additional bands. An unencapsulated Hib mutant still lacked C3 bound to the 98-kDa or P6 OMP, indicating that the absence of C3 binding to these proteins was not the result of epitope masking by the capsule. Studies with MAbs to C3 fragments confirmed that the anti-P1- and anti-P2-reactive bands were C3 fragments bound to these OMPs. The molecular weights of proteins reactive to anti-OMP and anti-C3 antibodies indicated that multiple C3 fragments may be bound to P1 or that C3 may be bound to P2 multimers. Finally, the presence of other anti-C3-reactive proteins indicated that several other proteins serve as C3 targets during the opsonization of Hib.

Amino Acid Sequence↗
PubMed1993

Modulating effect of dietary carbohydrate supplementation on Candida albicans colonization and invasion in a neutropenic mouse model.

We studied the effect of dietary carbohydrate supplementation on Candida albicans colonization and invasion of the gastrointestinal tract in a neutropenic mouse model. Mice inoculated with C. albicans were allowed free access to standard chow and drinking water supplemented with either glucose or xylitol or no carbohydrates (control). On days 33 through 36 postinoculation, the mean +/- standard error log10 CFU of C. albicans per gram on the mucosal surface, determined by quantitating CFU dislodged in the first wash of the gastric wall, was significantly higher in mice given the glucose supplement: 7.20 +/- 0.09 (glucose) versus 5.38 +/- 0.28 (xylitol) and 5.11 +/- 0.33 (control) CFU/g (P < or = 0.05 for each comparison by Fisher's protected least-significant-difference test). Fecal cultures also yielded the highest quantities of C. albicans in the glucose group. Invasion of the gastric wall by C. albicans correlated well with surface colonization in glucose-supplemented animals. Eight of 10 mice in this group, all with > 10(6) CFU/g, showed extensive invasive growth, as compared with only 2 of 26 mice in the remaining groups (P = 0.00006 by Fisher's exact test). These results indicate that dietary glucose intake is a key determinant of C. albicans growth in the gastrointestinal tract. The data provide an experimental rationale for clinical trials to decrease the intake of glucose or its utilization by C. albicans in immunocompromised patients.

Animals↗
PubMed1993

Cervical adenitis caused by Staphylococcus epidermidis.

Staphylococcus epidermidis, a human commensal, is a common cause of bacteremia in immunocompromised patients with indwelling medical devices. We report a case of isolated cervical adenitis caused by S. epidermidis in an immunocompetent patient and comment on the presumed pathogenesis.

Anti-Bacterial Agents↗
PubMed1993

Complement binding to Aspergillus conidia correlates with pathogenicity.

Complement has significant effects on the phagocytosis of Aspergillus organisms. We examined the amount and type of complement component C3 bound to the resting conidia of 29 isolates from nine Aspergillus species. The highly pathogenic species A. fumigatus and A. flavus bound fewer C3 molecules per unit of conidial surface area than did the less pathogenic species A. glaucus, A. nidulans, A. niger, A. ochraceus, A. terreus, A. versicolor, and A. wentii, as determined by quantitative flow cytometry. Immunoblot analysis of C3 fragments bound to conidia demonstrated that for all species most C3b was apparently converted to iC3b. For seven species, iC3b was clearly the major C3 product recognized by immunoblotting. However, A. niger and A. nidulans appear to promote further breakdown of opsonic C3 fragments to C3dg. We found significant variations in size and C3 binding among isolates within the same species. Intraspecies variation may contribute to seemingly discrepant results obtained in studies of Aspergillus phagocytosis.

Adult↗
PubMed1992

Complement component 3 binding to Haemophilus influenzae type b in the presence of anticapsular and anti-outer membrane antibodies.

Antibodies directed against the capsular polysaccharide (polyribosyl ribitol phosphate [PRP]) or the outer membrane proteins (OMP) of Haemophilus influenzae type b (Hib) promote bactericidal activity, complement 3 (C3) binding, and ingestion by phagocytic cells. To assess the relative contribution of anti-OMP to host defense against Hib, we compared the opsonic activities of anti-PRP and anti-OMP as reflected by the amounts of C3 bound to the bacterial surface. Immunoglobulin G (IgG) fractions containing either anti-PRP or anti-OMP were incubated with Hib in the presence of a C5-deficient complement source. C3, total IgG, and IgG subclasses bound to the bacteria were quantified by enzyme-linked immunosorbent assay. The maximum amount of C3 which could be bound to Hib was greater in the presence of anti-PRP than in the presence of anti-OMP. Also, except at low IgG concentrations, the rate of increase in bound C3 as a function of increasing IgG concentration was greater for anti-PRP than for anti-OMP. Hib-bound anti-OMP consisted primarily of IgG1 and IgG3, whereas bound anti-PRP was primarily IgG1 and IgG2. Thus, the potential for C3 binding to Hib is greater in the presence of anti-PRP than in the presence of anti-OMP, probably because of the larger number of binding sites available to the former. Nonetheless, OMP appear to provide important targets for opsonic antibody and would be logical components of a PRP-conjugate vaccine or may be efficacious as vaccines against nontypeable H. influenzae.

Bacterial Outer Membrane Proteins↗
PubMed1992

Role of the Staphylococcus epidermidis slime layer in experimental tunnel tract infections.

An experimental animal model was used to assess the slime layer of Staphylococcus epidermidis as a pathogenic factor in tunnel tract infections. Mice were inoculated with high-slime-producing or non-slime-producing strains of S. epidermidis, either along the length of a subcutaneous catheter or in the area where a catheter had been placed and immediately removed (controls). Among the catheter-bearing mice, the phenotypically distinct staphylococci produced similar, high frequencies of abscess formation (72% [44 of 61] versus 81% [31 of 38]; P = 0.29). In controls, the non-slime-producing organisms were significantly more pathogenic (87% [40 of 46] versus 57% [25 of 44] abscess formation; P = 0.001). No consistent difference was detected between blood isolates obtained from patients with central venous catheter bacteremia and those from neonates with bacteremia in the absence of a prosthetic medical device. Quantitative culture of removed catheters showed greater adherence by the slime-producing isolates (P = 0.014). In this mouse model, slime production by S. epidermidis did not increase the risk of catheter tunnel tract infection, despite the greater catheter adherence of the slime-producing organisms. These findings suggest that traumatized tissue may be a sufficient condition for the development of S. epidermidis catheter-associated infections.

Abscess↗
PubMed1991

Management of anorectal/perineal infections caused by Pseudomonas aeruginosa in children with malignant diseases.

The role of operation for anorectal infections associated with perineal gangrene and cellulitis in children with myelo-suppression from cancer chemotherapy is unclear. We evaluated anorectal/perineal infections caused by Pseudomonas aeruginosa in 16 children with malignant diseases seen over 27 years. In 12 of 16 patients, leukemia was the underlying malignancy (ALL 10, AML 2), and in 13 of 16, severe neutropenia (absolute neutrophil count less than 500/mm3) was present at diagnosis. Cultures of the lesions showed multiple organisms in 14 of 16 patients with Escherichia coli, Klebsiella species, and Enterococcus being the most frequent coexisting organisms. All positive blood cultures grew P aeruginosa exclusively. Of three patients with necrotizing infections, two had complete resolution with medical treatment alone; the other patient who developed this problem while on terminal care died. In none of the 16 patients was a major operation (debridement or diversion) performed. Five patients died, three of whom were considered terminally ill when the anorectal infections occurred. Four of the five deaths occurred before 1974. Since then, only 1 of 7 patients died. Excluding the three terminally ill patients, the success rate of medical therapy alone is 85% (11/13). The antibiotic regimen should include an aminoglycoside in synergistic combination with anti-Pseudomonas penicillin. These results suggest that operative management may have no role in the management of anorectal infections caused by P aeruginosa in children with cancer.

Administration, Topical↗
PubMed1991

Pseudomonas aeruginosa cellulitis and ecthyma gangrenosum in immunocompromised children.

Pseudomonas aeruginosa skin infections are generally considered to be secondary manifestations of disseminated disease. A retrospective analysis of all cases of P. aeruginosa skin infections seen at St. Jude Children's Research Hospital since 1962 revealed 16 episodes of the infection (ecthyma gangrenosum, 8 episodes, 7 patients; cellulitis, 8 episodes, 7 patients) in which blood cultures were uniformly negative for P. aeruginosa. All cases were identified while the patients were receiving ambulatory care. Five episodes developed while the patients' neutrophil counts were greater than 1 x 10(9) cells/liter. Eight patients had acute lymphoblastic leukemia, 2 had acute myeloid leukemia, 2 had aplastic anemia, 1 had transient agranulocytosis and 1 had cyclic neutropenia. There were no solid tumor patients. Although patients received different antibiotic combinations, all had resolutions of their lesions without fatal complications. Patients diagnosed as having cellulitis required a mean of 9.2 days of treatment with intravenous antibiotics, as compared with 17.8 days for those with ecthyma gangrenosum (P less than 0.05 by the Wilcoxon test). These observations show that P. aeruginosa skin infections can develop in the absence of bacteremia in immunocompromised children.

Adolescent↗
PubMed1991

Identification of the innate human immune response to surface-exposed proteins of coagulase-negative staphylococci.

The presumed host defense against coagulase-negative staphylococci (ConS), recognized pathogens in hosts with compromised immunity or indwelling medical devices, is opsonophagocytosis. Targets for opsonization remain unclear. Using radiolabeling techniques, we identified the surface-exposed proteins of ConS and determined the innate humoral immune responses to them among healthy adults. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of surface proteins extrinsically labeled with 125I demonstrated 20 to 30 proteins with molecular weights of 15,000 to greater than 130,000. Five to ten of these proteins were immunogenic and recognized by normal human sera, including predominant 18-, 41-, 48-, and 51-kDa proteins. We also evaluated the humoral response of cancer patients with ConS bacteremia. Patients' sera obtained before bacteremic episodes demonstrated a pattern of reactivity similar to that of normal human sera. When patients' sera obtained after bacteremic episodes were used to determine whether an expanded immune response followed infection, only one of seven showed reactivity with more proteins than seen with the innate response. Western blot (immunoblot) analysis and whole-cell enzyme-linked immunosorbent assays were also evaluated. This study identifies (i) the surface-exposed proteins available for host interaction, (ii) the innate human antibody response to these proteins, and (iii) the immune response of cancer patients with ConS bacteremia.

Adolescent↗