[Delayed hypersensitivity reaction in staphylococcal infections. 1. Delayed cutaneous reaction by staphylococcal cell wall material (mucopeptide)].
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An outbreak of staphylococcal skin infection in neonates was investigated clinically, bacteriologically and epidemiologically with the following findings: (1) In 8 out of 13 cases, exfoliatin-producing staphylococci were present in the bullae, which is unusual with bullous lesions occurring at other ages; (2) exfoliatin producing staphylococci were present in all children with bullous lesions, as well as in carriers; (3) 39% of the phage II group staphylococci studied produced exfoliatin; (4) purulent lesions due to phage II staphylococci which did not produce exfoliatin were observed. The contaminating agent could be identified in most cases.
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BACKGROUND: Oral combination therapy with fluoroquinolones plus rifampicin is a promising alternative to standard parenteral therapy for staphylococcal infections. METHODS: In a multicenter, randomized trial, we compared the efficacy, safety, and length of hospital stay for patients with staphylococcal infections treated either with an oral combination of a fluoroquinolone (fleroxacin) plus rifampicin or with standard parenteral treatment (flucloxacillin or vancomycin). Patients were included if cultures showed the presence of bacteremia or deep-seated infections with Staphylococcus aureus (104 patients) or catheter-related bacteremia due to drug-susceptible, coagulase-negative staphylococci (23 patients). RESULTS: The cure rate in the intention-to-treat analysis was 78% for the fleroxacin-rifampicin group (68 patients) and 75% for the standard therapy group (59 patients; 47 received flucloxacillin, and 12 received vancomycin); in the population of clinically evaluable patients (n=119), the cure rate was 82% and 80%, respectively; and in the population of microbiologically evaluable patients (n=103), the cure rate was 86% and 84%, respectively. Clinical and bacteriological failures after S. aureus infections were documented in similar proportions of patients. The median length of hospital stay after study entry was 12 days in the fleroxacin-rifampicin group, compared with 23 days in the standard treatment group (P=.006). More adverse events probably related to the study drug were reported in the fleroxacin-rifampicin group than in the standard therapy group (15 of 68 vs. 5 of 59 patients; P=.05). CONCLUSIONS: This study suggests that an oral regimen containing a fluoroquinolone plus rifampicin may be effective for treating staphylococcal infections, allowing earlier discharge from the hospital.
The influence of trypsin on the formation of immune response induced by a thymus-dependent antigen at different periods of localized staphylococcal infection has been studied. A single intramuscular injection of bovine trypsin has been found to enhance immune response to sheep red blood cells (SRBC) in healthy mice and, to a still greater degree, in mice with localized staphylococcal infection. the development of localized staphylococcal infection has been shown to have no influence on the manifestation of the immuno-suppressive effect of splenocytes in SRBC-immunized mice or to enhance this effect. The injection of trypsin decreases the immunosuppressive effect of splenocytes in healthy or staphylococcus-infected hyperimmune mice.
The effect of leucomycin, chimotrypsin and their combination on the leucocyte phagocytic activity was studied on mice with experimental staphylococcal infection. Lincomycin and chimotrypsin were administered in doses of 150 and 2 mg/kg respectively. In the study of the leucocyte phagocytic activity it was found on the 3rd, 7th, 14th and 21st days after the beginning of the animal infection and treatment that the experimental staphylococcal infection stimulated the non-specific phagocytosis. Lincomycin inhibited the leucocyte phagocytic activity. The use of chimotrypsin in the process of the staphylococcal infection treatment resulted in increased phagocytosis activity. The combined use of chimotrypsin and leucomycin decreased the inhibitory effect of the latter on phagocytosis.
A survey of the staphylococcal infections occurring in a general hospital over a period of four and a half years showed that multiple-resistant strains of phage type 77 were endemic in the medical and surgical wards. Strains of this phage type were uncommon among patients attending the casualty department, and those found were usually either fully sensitive to antibiotics or resistant to benzylpenicillin only. Regular monitoring of patients admitted to the intensive-care unit showed that 58% of staphylococcal infections in such patients were present at the time of admission to the unit. Although the wards thus constituted a significant reservoir of infection for the intensive-care unit, there was no evidence to suggest that the return of patients from the unit to the wards was responsible for the transfer of infection in the opposite direction. The possibility of reducing the numbers of multiple-resistant staphylococci in the general wards, by the screening of all new admissions for the presence of tetracycline-resistant strains, appears to be impracticable in this area.
The authors report the results of more than twelve years' personal research on the value of anti-alphahemolysin (AASTL) and antigammahemolysin (AGSTL) assays for the diagnosis of staphylococcal infections, and particularly of osteoarthritis. Among 574 controls, AASTL levels exceeded 2 IU in only 14 subjects (11 of these, levels were between 2 and 3 IU). Levels less than, or equal to, 2 IU were therefore considered normal. This is consistent with previously published data. In 144 staphylococcal infections, confirmed by bacteriology, an increase in AASTL was found in 95 of all cases (65.9%) and in 54 of the 76 osteoarthritis' (71%). Similarly, AGSTL titres, which were under 1/160 (upper normal limit) in 138 controls, were increased in 35 patients with unequivocal staphylococcal infections (61.4%), and in 25 of 36 patients with osteoarthritis (69.4%). These results show that AASTL assay is reliable and often abnormal. However, assay of both hemolysins yields even better results. This dual assay was performed in 57 patients with staphylococcal infection. One hemolysin at least was increased in 47 patients (82.4%). This represents additional positivity in 15.7% of patients when compared to AASTL assay alone, and in 21% when compared to AGSTL assay alone. The high level of positive results with dual assay is even more striking when only staphylococcal osteoarthritis is considered: one or both hemolysins were increased in 91.1% of these patients (31/34).
Forty-two cases of severe staphylococcal infection occurring over a 10-year period in the neonatal unit at Queen Mary Hospital are described. There was a 4.5-fold increase in incidence in the latter half of the study period, when methicillin-resistant Staphylococcus aureus (MRSA) emerged. The isolated MRSA were also resistant to gentamicin, but sensitive to vancomycin, fusidic acid, co-trimoxazole and amikacin. Comparison between MRSA and methicillin-sensitive cases showed that the former was associated with a longer hospital stay after diagnosis. Overall mortality was 9.5%. Two cases with meningitis died. MRSA is at least as virulent as its methicillin-sensitive counterparts. The treatment implications of severe neonatal staphylococcal infection are discussed.
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Staphylococcal infection of a vascular prosthesis is a relatively uncommon complication of peripheral vascular surgery; however, these infections and their sequelae can be catastrophic. The majority of prosthetic graft infections are caused by mucin-producing strains of Staphylococcus epidermidis, which express varying degrees of adherence to the synthetic substrates. Studies have demonstrated that the components and construction characteristics of the graft, implantation site, administration of antimicrobial agents, and endogenous microbial flora are all identifiable risk factors in vascular graft infections. Mucin production, a known virulence factor, has recently been shown to occur in endogenous coagulase-negative staphylococci (CNS) at the time of hospital admission. While mucin production plays an important role in the persistence of graft infections, there is no evidence that suggests a relationship between mucin and antimicrobial resistance. Identifying characteristics of (CNS) graft infections may include a draining wound sinus, poor graft incorporation, a perigraft exudate or a pseudoaneurysm at the anastomotic site. The occult nature of these infections, in which the patient is often asymptomatic, makes diagnosis and treatment difficult. The graft or graft exudate may be negative when routine culture methods are employed. The recognition of CNS graft infections requires a high index of suspicion and the treatment of these infections requires understanding of the pathogenic process, individualized surgical management, and the judicious use of antimicrobial agents.
There is a high incidence of staphylococcal infection in children with dermatomyositis, which is limited to those children who either already have or subsequently develop calcinosis. Of 15 children followed up for 3-10 years after diagnosis, all nine who developed calcinosis had infections with Staphylococcus aureus compared with none of six without calcinosis. Of these nine, the occurrence of staphylococcal infections before calcinosis was observed in four, suggested by history in two, and unclear in three children. Granulocyte chemotaxis to Staphylococcus aureus was more severely depressed in those children with calcinosis, whereas those without calcinosis did not differ significantly from controls. The chemotactic defect was due to a serum factor (patients' serum depressed control chemotaxis and control serum corrected the patients' chemotaxis). The nine children with calcinosis also had significantly higher serum IgE concentrations than non-atopic age matched controls; the six without calcinosis did not differ from controls. The increased IgE concentrations appeared to develop after staphylococcal infection and before calcinosis. Two of five patients with calcinosis had increased antistaphylococcal IgE antibodies; neither of the two patients without calcinosis had such increased antibodies. This suggests preceding immunological differences in patients with dermatomyositis who do and do not subsequently develop calcinosis, either increasing susceptibility to Staphylococcus aureus infection or potentially resulting from such infections.
Vancomycin was developed in the 1950s, when available therapy for severe staphylococcal infections was unsatisfactory. Early clinical experiences with vancomycin indicated a cure rate of 70%. The introduction of beta-lactamase-resistant penicillins and cephalosporins, which have a lower potential for toxicity, resulted in limited use of vancomycin. The current renewal of interest in vancomycin for treatment of severe staphylococcal infections stems primarily from the efficacy of this drug against methicillin-resistant pathogens and its utility in a number of unique clinical situations. In addition, the development of more purified preparations of vancomycin has lowered the frequency of adverse side effects.
BACKGROUND: This is a retrospective study on the efficacy and safety of arbekacin (ABK), an aminoglycoside antibiotic, for acquired staphylococcal infection in the neonatal intensive care nursery. PATIENTS AND METHODS: Subjects were 29 infants treated with ABK in a tertiary care neonatal center. They were 23-39 (median 28) weeks' gestation, 530-3334 (median 930) grams at birth, and 3-157 (median 17) days of age. Diagnosis of staphylococcal infection was made by clinical signs and laboratory findings. Sensitivity of the isolated organisms to ABK was tested by the microliquid dilution method. Serum ABK level was monitored to achieve the therapeutic range during the treatment. Effectiveness was defined by improving clinical signs and laboratory findings within 3 days. Effectiveness was studied in relation to type of infection and other antibiotics administered. Auditory brainstem response and serum creatinine changes were studied for ototoxicity and nephrotoxicity assessment, respectively. RESULTS: Twenty-seven (93.1%) cases of infection were attributed to methicillin-resistant Staphylococcus aureus (MRSA) and two (6.9%) were attributed to coagulase-negative staphylococci (CNS). The rate of in vitro sensitivity to ABK was 85.2% for MRSA and 100.0% for CNS. The overall clinical effeciveness rate was 79.3% (23/29) with no difference associated with types of infection. Combination of ABK with sulbactam/ampicillin showed greater effectiveness (100.0%) than with other antibiotics (64.3%) (P < 0.05). There was no abnormal auditory brainstem response or serum creatinine change associated with ABK treatment. CONCLUSION: ABK is an effective and safe antibiotic for the treatment of acquired staphylococcal infection in the neonatal intensive care nursery.
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In a prospective, randomized study of staphylococcal infections, 27 patients received oxacillin plus rifampin and 29 received oxacillin alone. Vancomycin was substituted for oxacillin when the pathogen was demonstrated to be resistant to oxacillin in vitro. Infection was cured in 18 (67%) of the 27 patients receiving oxacillin (or vancomycin) plus rifampin and in 12 (41%) of the 29 receiving oxacillin (or vancomycin) alone (P less than .01). The clinical effect of the addition of rifampin to oxacillin (or vancomycin) was beneficial in spite of a rifampin-associated reduction in the bactericidal activity of serum containing high concentrations of oxacillin.
Intracutaneous and intravenous injection of pyrogenic, non-lethal doses of bacterial endotoxin were found to increase the infectivity of pathogenic but not non-pathogenic staphylococci in rabbit skin. The increased infectivity of the microorganism was characterized by accelerated multiplication at the site of inoculation and by the production of necrosis and hemorrhage locally. Histologically, the infection of skin in endotoxin-prepared animals was characterized by necrosis, masses of bacteria, but absence of leukocytic infiltration into the area of bacterial growth. The infectivity of staphylococci in skin of endotoxin-prepared rabbits could be controlled by antibody to the alpha hemolysin of the microorganism. The effect of endotoxin upon staphylococcal infection was demonstrable only within 4 hours after injection of the endotoxin. It could not be prevented with chlorpromazine or dibenamine and was closely related to the effect of endotoxin upon leukocytes. It was suggested that the effect of endotoxin upon leukocytes was probably responsible for its influence upon staphylococcal infection. The implications of these findings in the pathogenesis of staphylococcal infection are discussed.