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PubMed1965

BIOCHEMICAL EFFECTS OF NOVOBIOCIN ON STAPHYLOCOCCUS AUREUS.

Wishnow, Rodney M. (Washington University School of Medicine, St. Louis, Mo.), Jack L. Strominger, Claire H. Birge, and Robert H. Threnn. Biochemical effects of novobiocin on Staphylococcus aureus. J. Bacteriol. 89:1117-1123. 1965.-Novobiocin induced accumulation in Staphylococcus aureus of uridine nucleotide precursors of the cell-wall glycopeptide, of a cytidine nucleotide precursor of the teichoic acid in the cell wall, and of a large number of other ultraviolet-absorbing materials. These substances accumulated promptly on addition of the antibiotic at levels near the growth-inhibitory concentration. Isotopic experiments showed that, in addition to inhibiting cell-wall synthesis, novobiocin also inhibited both protein and nucleic acid synthesis. The lack of selectivity in the action of novobiocin is similar to that previously observed with gentian violet, and is quite different from the selective inhibition of cell-wall synthesis observed with penicillin or with d-cycloserine. Although inhibition of cell-wall synthesis is not excluded as one of the primary lethal effects of novobiocin, it is also possible that all of the observed phenomena are secondary to some other primary metabolic lesion.

Anti-Bacterial Agents↗

PubMed1965

NUCLEOTIDE ACCUMULATION INDUCED IN STAPHYLOCOCCUS AUREUS BY GLYCINE.

Strominger, Jack L. (Washington University School of Medicine, St. Louis, Mo.), and Claire H. Birge. Nucleotide accumulation induced in Staphylococcus aureus by glycine. J. Bacteriol. 89:1124-1127. 1965.-High concentrations of glycine induce accumulation of four uridine nucleotides in Staphylococcus aureus. Investigations of their structure suggest that these compounds are uridine diphosphate (UDP)-acetylmuramic acid, UDP-acetylmuramyl-gly-d-glu-l-lys, UDP-acetylmuramyl-l-ala-d-glu-l-lys and UDP-acetylmuramyl-gly-d-glu-l-lys-d-ala-d-ala. The mechanism by which glycine may induce uridine nucleotide accumulation and protoplast formation is discussed.

Dipeptides↗

PubMed1965

NATURE AND INTERACTIONS OF THE GENETIC ELEMENTS GOVERNING PENICILLINASE SYNTHESIS IN STAPHYLOCOCCUS AUREUS.

Novick, Richard P. (The Rockefeller Institute, New York, N.Y.), and Mark H. Richmond. Nature and interactions of the genetic elements governing penicillinase synthesis in Staphylococcus aureus. J. Bacteriol. 90:467-480. 1965.-It has been found previously that penicillinase-producing strains of Staphylococcus aureus each harbor an extrachromosomal element, or plasmid, which apparently carries all the genetic information necessary for penicillinase synthesis. These plasmids behave in a manner consistent with their being small chromosomelike structures in that they comprise linkage groups containing several markers and in that they undergo such genetic events as mutation, segregation, and recombination. There is currently no evidence for conjugal cell-cell transfer of the plasmids or for a state of stable integration into the staphylococcal chromosome. A certain amount of variability has been encountered among the penicillinase plasmids harbored by different staphylococcal strains. It has been found that: (i) there are at least three molecular variants of the enzyme itself; (ii) most, but not all, of the penicillinase plasmids carry a genetic determinant of resistance to mercuric ion; (iii) plasmids carried by a very small number of the strains bear a determinant of resistance to erythromycin; (iv) the plasmids determine the fraction of penicillinase excreted into the medium during growth, and this also varies from strain to strain. The penicillinase plasmids appear to behave as integral genetic structures. The entire known linkage group is transduced intact, and is occasionally lost completely as a spontaneous occurrence during the growth of the organisms. Rarely, the plasmid markers dissociate during transduction, resulting in transduced clones which have inherited only a part of the plasmid linkage group. Similarly, dissociation occurs as a spontaneous event during normal growth, also resulting in rare clones which appear to have lost one or more but not all of the plasmid markers. When crosses are performed between two plasmid-harboring strains, a plasmid heterozygote is formed. In most cases, this persists for only one or a few cell divisions before segregating, with or without the formation of recombinant plasmids. In two instances thus far observed, the heterozygote persists as a stable plasmid heterodiploid, in which the continued presence of both plasmids can be readily demonstrated. The fate of the heterozygote, i.e., early segregation or persistence as a heterodiploid, depends upon which particular pair of plasmids is involved in the cross. This observation has led to the hypothesis of a plasmid-linked determinant of plasmid compatibility. A pair of plasmids is considered compatible if it can form a stable heterodiploid, incompatible if it cannot.

Cell Division↗

PubMed1984

Identification of Staphylococcus species of bovine origin with the DMS Staph-Trac system.

The DMS Staph-Trac system was evaluated as a means for identifying the species of bovine strains of staphylococci routinely isolated from quarter-milk samples. The species identity of 83 of 91 (91.2%) isolates of staphylococci was correctly determined by this method. One isolate could not be identified by this system. The Staph-Trac system was able to distinguish between Staphylococcus hyicus and Staphylococcus epidermidis. We obtained a higher percentage of correct identifications with the DMS Staph-Trac system (91.2%) than we did in a previous study with the API Staph-Ident system (45.1%), using the same isolates (Langlois et al., J. Clin. Microbiol. 18:1212-1219, 1983).

Animals↗

PubMed2004

Simultaneous PCR detection of ica cluster and methicillin and mupirocin resistance genes in catheter-isolated Staphylococcus.

Recent data show that more than 50% of catheter-associated bloodstream infections are caused by staphylococci. Staphylococcal infections produced by intercellular-adhesion cluster (ica) carriers can be even more problematic due to the presence of methicillin and mupirocin resistance genes. In the present study, a multiplex PCR protocol that allows the simultaneous identification of staphylococci and detection of both the ica and methicillin and/or mupirocin resistance genes was developed. Furthermore, the method allows differential detection of the ica locus from Staphylococcus aureus and Staphylococcus epidermidis.

Base Sequence↗

PubMedDate not supplied

The burden of Staphylococcus aureus infections on hospitals in the United States: an analysis of the 2000 and 2001 Nationwide Inpatient Sample Database.

BACKGROUND: Previous studies have investigated the impact of Staphylococcus aureus infections on individual hospitals, but to date, no study using nationally representative data has estimated this burden. METHODS: This is a retrospective analysis of the 2000 and 2001 editions of the Agency for Healthcare Research and Quality's Nationwide Inpatient Sample database, which represents a stratified 20% sample of hospitals in the United States. All inpatient discharge data from 994 hospitals in 28 states during 2000 and from 986 hospitals in 33 states during 2001, representing approximately 14 million inpatient stays, were analyzed to determine the association of S aureus infections with length of stay, total charges, and in-hospital mortality. RESULTS: Staphylococcus aureus infection was reported as a discharge diagnosis for 0.8% of all hospital inpatients, or 292 045 stays per year. Inpatients with S aureus infection had, on average, 3 times the length of hospital stay (14.3 vs 4.5 days; P<.001), 3 times the total charges (48,824 US dollars vs 14,141 US dollars; P<.001), and 5 times the risk of in-hospital death (11.2% vs 2.3%; P<.001) than inpatients without this infection. Even when controlling for hospital fixed effects and for patient differences in diagnosis-related groups, age, sex, race, and comorbidities, the differences in mean length of stay, total charges, and mortality were significantly higher for hospitalizations associated with S aureus. CONCLUSIONS: Staphylococcus aureus infections represent a considerable burden to US hospitals, particularly among high-risk patient populations. The potential benefits to hospitals in terms of reduced use of resources and costs as well as improved outcomes from preventing S aureus infections are significant.

Age Factors↗

PubMed1987

Role of internal fixation in infection of open fractures: studies with Staphylococcus aureus and Proteus mirabilis.

Studies of infections in open fractures are described. The hamster was chosen as the experimental model. Osteotomies of the femur were created with an osteotomy saw. Some osteotomies were left to heal and others were fixed with an 0.9 mm K-wire. The infection rates in fixed and unfixed fractures were compared. The first group of hamsters with fixed and unfixed osteotomies was returned to cages with open wounds. There was no difference in the infection rate at 2 weeks. The second group was deliberately contaminated with Staphylococcus aureus and then returned to cages with open wounds. In this group, the infection rate at 2 weeks was lower in the internally-fixed fractures than in the unfixed fractures. The third group was deliberately contaminated with the gram negative organism Proteus mirabilis. In these animals, the infection rate was increased in the presence of the internal fixation device. The fourth group was deliberately contaminated with both Staphylococcus aureus and Proteus mirabilis. The infection rate in these animals was very high; Proteus was recovered from those animals with internal fixation and Staphylococcus was recovered from those animals without internal fixation. These studies in the hamster document the usefulness of this animal as an inexpensive and reproducible model for studying infection of open fractures. The hamsters tolerated the procedure well, and wound and fracture healing progressed satisfactorily.

Animals↗

PubMed1999

Iatrogenic staphylococcus aureus septicaemia following intravenous and intramuscular injections: clinical course and pathomorphological findings.

The clinical course, autopsy and histological findings are presented from three (one 33-year-old female and two males aged 26 and 56) fatalities resulting from injection therapy which has produced Staphylococcus aureus septicaemia. The autopsies were performed within 2-4 days postmortem. No primary focus other than the insertion site of the peripheral venous catheters or the intramuscular injections, representing the initial entry site of Staphylococcus aureus, could be identified. Death was attributed directly to the staphylococcal infection as a result of iatrogenic injection therapy for the treatment of a non-severe underlying illness (premature labour pains, acute loss of hearing, lumbago). The forensic diagnosis of Staphylococcus aureus septicaemia following iatrogenic injections has to be critically evaluated and can be established routinely in cases with delayed autopsy only when no other cause of death is revealed by autopsy, no apparent source of infection other than the insertion site can be detected and careful attention is paid to histological and bacteriological findings. All doubtful cases of nosocomial bloodstream infections with fatal outcome should undergo an immediate autopsy. In cases of very early forensic involvement microbiological investigations, including phagotyping, molecular biological characterization and identification of bacterial toxins from micro-organisms out of appropriate specimens obtained postmortem, could be efforts of potential evidential value regarding the aetiological proof. To optimize aetiopathogenetic conclusions concerning a causal relationship between iatrogenic injections and septic complications, the medicolegal investigation should also include an interdisciplinary co-operation with consultants from other relevant fields (e.g. microbiology and hygienics).

Adult↗

PubMed2005

[Methicillin resistant Staphylococcus aureus bacteremia seven years of survey in a French hospital].

In our French general hospital with 1000 hospitalization beds, a specific isolation for multiresistant bacteria colonized or infected patients was set up since 1998. To assess the impact of these recommendations, the rate of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia was calculated for each year since 1998. From 1998 to 2004, 493 cases of Staphylococcus aureus (SA) bacteremia occurred in our hospital: 319 strains were susceptible to methicillin and 174 were MRSA. During the 7 years period of our study, we observed a significant tendency for reduction in the number of bacteremia with MRSA strains (p=0.016). The significant decrease of the MRSA bacteremia between 1998 and 2004 was obtained through the cooperation between staff members, bacteriologists and hospital nosocomial infection committee members.

Bacteremia↗

PubMed1993

Perinephric abscess due to a coagulase-negative Staphylococcus: case report and review of the literature.

Perinephric abscess is an uncommon urinary tract infection that usually is caused by Staphylococcus aureus as a single pathogen or gram-negative bacilli as part of a polymicrobial process. We describe a man who presented with a right perinephric abscess due to coagulase-negative Staphylococcus as the only pathogen. The patient had bilateral nephrolithiasis, and he was treated successfully with percutaneous drainage of the abscess and parenteral antibiotics. Coagulase-negative staphylococci are increasingly reported to cause serious infections. This organism can no longer be routinely dismissed as a contaminant or colonizer. Repeated isolation of coagulase-negative Staphylococcus in the absence of other pathogens must be considered a high risk situation.

Abscess↗

PubMed2002

Treatment with staphylococcus toxoid in fibromyalgia/chronic fatigue syndrome--a randomised controlled trial.

We have previously conducted a small treatment study on staphylococcus toxoid in fibromyalgia (FM) and chronic fatigue syndrome (CFS). The aim of the present study was to further assess the efficacy of the staphylococcus toxoid preparation Staphypan Berna (SB) during 6 months in FM/CFS patients. One hundred consecutively referred patients fulfilling the ACR criteria for FM and the 1994 CDC criteria for CFS were randomised to receive active drug or placebo. Treatment included weekly injections containing 0.1 ml, 0.2 ml, 0.3 ml, 0.4 ml, 0.6 ml, 0.8 ml, 0.9 ml, and 1.0 ml SB or coloured sterile water, followed by booster doses given 4-weekly until endpoint. Main outcome measures were the proportion of responders according to global ratings and the proportion of patients with a symptom reduction of > or =50% on a 15-item subscale derived from the comprehensive psychopathological rating scale (CPRS). The treatment was well tolerated. Intention-to-treat analysis showed 32/49 (65%) responders in the SB group compared to 9/49 (18%) in the placebo group (P<0.001). Sixteen patients (33%) in the SB group reduced their CPRS scores by at least 50% compared to five patients (10%) in the placebo group (P< 0.01). Mean change score on the CPRS (95% confidence interval) was 10.0 (6.7-13.3) in the SB group and 3.9 (1.1-6.6) in the placebo group (P<0.01). An increase in CPRS symptoms at withdrawal was noted in the SB group. In conclusion, treatment with staphylococcus toxoid injections over 6 months led to significant improvement in patients with FM and CFS. Maintenance treatment is required to prevent relapse.

Adolescent↗

PubMed1998

Effects of staphylococcus toxoid vaccine on pain and fatigue in patients with fibromyalgia/chronic fatigue syndrome.

Positive results of pilot studies of the effect of staphylococcus toxoid vaccine in patients with fibromyalgia and chronic fatigue syndrome were the incitement to the present, placebo-controlled study. It included 28 patients who fulfilled the criteria for both fibromyalgia and chronic fatigue syndrome. The effect of vaccination with a staphylococcus toxoid was compared with the effect of injections of sterile water. Psychometric assessment was made using 15 items from the comprehensive psychopathological rating scale (CPRS), Zung's self-rating depression scale and clinical global impressions (CGI). The visual analogue scale (VAS) was used to measure pain levels, and a hand-held electronic pressure algometer was used to measure pressure pain thresholds. Significant improvement was seen in seven of the 15 CPRS items in the vaccine group when pretreatment values were compared to post-treatment values. In CPRS < >, there were significant intergroup differences, and in CPRS < > intergroup differences bordered on significance. There was no significant improvement in CPRS items in the placebo group. Clinical global impressions showed significant improvement in the vaccine-treated group, and VAS did so in both groups. In a follow-up study of 23 patients, the vaccine treatment was continued for 2-6 years. Fifty percent were rehabilitated successfully and resumed half-time or full-time work. The results of this study support the authors>> hypothesis that treatment with staphylococcus toxoid may be a fruitful strategy in patients with fibromyalgia and chronic fatigue syndrome. Copyright 1998 European Federation of Chapters of the International Association for the Study of Pain.

Journal Article↗

PubMed2002

Clinically significant concentrations of local anesthetics inhibit Staphylococcus aureus in vitro.

This study explores which concentrations of local anesthetics might be expected to inhibit the growth of Staphylococcus aureus. Serial dilutions were made of 0.5% and 0.75% bupivacaine, 2% and 5% lidocaine, 2% and 3% chloroprocaine, and 0.2% and 1% ropivacaine. To each concentration of local anesthetic solution, Mueller Hinton broth medium and Staphylococcus aureus were added. The resulting solutions were incubated and then observed for growth 24 and 48 h later. The minimum concentrations of the local anesthetics that could inhibit growth of Staphylococcus aureus were 0.25% bupivacaine, 1.25% lidocaine and 0.75% chloroprocaine. The inhibitory concentration of ropivacaine could not be determined because the more concentrated solutions precipitated in the Mueller Hinton broth. Local anesthetics may help protect against epidural abscess formation if they are used in sufficiently high concentrations. This effect may help explain the very low reported incidence of epidural abscess.

Journal Article↗

PubMed1994

The current spectrum of Staphylococcus aureus infection in a tertiary care hospital.

Staphylococcus aureus remains a prominent cause of community- and hospital-acquired infection. This study reviewed 162 cases of S. aureus infection occurring in 120 adults who were hospitalized at a Veterans Affairs Medical Center and referred for consultation to the Infectious Disease Service. There were 37 cases of skin and soft tissue infection, 5 pyomyositis, 34 osteomyelitis, 13 septic arthritis, 19 pneumonia, 3 empyema, 5 pyelonephritis, 37 vascular infection, 3 epidural abscess, and 6 miscellaneous infections. Bacteremia was documented in 56 of 119 (47%) cases in which blood cultures were obtained, indicating the serious nature of the infections in many cases. Staphylococcus aureus is widely prevalent in healthy persons. Given its ubiquity and the capacity to cause a broad array of infections, an effective host response must play an important role in preventing infection. This host response is immunologically nonspecific, in that it depends upon the effectiveness of mechanical barriers to invasion and, once invasion takes place, the interaction of PMN, complement, and antibody that is probably present in serum of all immunologically competent adults rather than sensitization of B or T lymphocytes by any identifiable antigens specific to S. aureus. Analysis of the present cases calls attention to S. aureus as an opportunistic pathogen, 1 that only infrequently causes serious infection in otherwise healthy persons. Nearly every patient in this series had 1 or more medical condition thought to predispose to infection; 279 such conditions were identified, representing an average of 2.3 per person. A break in the natural barrier to infection was also present in the majority of cases, for example, trauma, wound, or pre-existing decubitus ulcer in skin and soft tissue infections; endotracheal tube in pneumonia; and a catheter bypassing urethra or skin in urinary and vascular infections, respectively. The tendency for patients to be infected with S. aureus repeatedly (mean number of infections, 1.4 per patient) reflects the chronicity of many predisposing factors and, perhaps, of colonization as well. Staphylococcus aureus has a special predilection to cause infections involving prosthetic devices, perhaps related to its affinity for fibronectin, laminin, and other serum proteins that can mediate attachment to foreign material; 46 of 162 (28%) infections were associated with the presence of a foreign body. Such infections are difficult to eradicate with antibiotic therapy alone, perhaps because of a change in the metabolic state of adherent bacteria, and removal of the foreign body is generally required for cure.(ABSTRACT TRUNCATED AT 400 WORDS)

Abscess↗

PubMed2000

Demonstration of intracellular Staphylococcus aureus in bovine mastitis alveolar cells and macrophages isolated from naturally infected cow milk.

Numerous in vitro studies have demonstrated that Staphylococcus aureus may be internalized and survive in a bovine mammary epithelial cell line. We report here the presence of internalized and living S. aureus in alveolar cells and macrophages in milk samples of bovine mastitis. We used fluorochrome labeled monoclonal antibodies, specifically recognizing surface cell markers of bovine alveolar cells and macrophages, to isolate these two types of cells using fluorescence activated cell sorting. Extracellular bacteria and DNA were previously eliminated to exclude possible contamination. In order to detect intracellular bacterial DNA inside the isolated cells, we used PCR amplification of bacterial DNA and the PCR products were analyzed by Southern blot with a specific probe for Staphylococcus. The results showed the presence of Staphylococcus DNA inside the two isolated populations of cells, confirming that S. aureus could penetrate alveolar cells and macrophages. The demonstration of the presence of intracellular living S. aureus was determined by bacteriological culture of positive samples plated onto blood agar plates and by its further identification. Our results showed for the first time that living S. aureus and its DNA are present in both alveolar cells and macrophages in chronically infected cow milk.

Animals↗

PubMed1998

Ambulatory treatment of multidrug-resistant Staphylococcus-infected orthopedic implants with high-dose oral co-trimoxazole (trimethoprim-sulfamethoxazole).

We examined the effectiveness and safety of high-dose oral co-trimoxazole (trimethoprim-sulfamethoxazole) for the treatment of orthopedic implants infected with multidrug-resistant Staphylococcus species. The prospective study was conducted between 1989 and 1997 in a university medical center with ambulatory-care services. Patients eligible for the study consisted of those from whom multidrug-resistant Staphylococcus spp. organisms susceptible only to glycopeptides and co-trimoxazole were isolated from their orthopedic implants and for whom there was no contraindication to the treatment. All patients were treated orally with high-dose co-trimoxazole (trimethoprim, 20 mg/kg of body weight/day; sulfamethoxazole, 100 mg/kg/day). Patients with prosthetic hip infections were treated for 6 months, with removal of any unstable prosthesis after 5 months of treatment; patients with prosthetic knee infections were treated for 9 months, with removal of any unstable prosthesis after 6 months of treatment; and patients with infected osteosynthetic devices were treated for 6 months, with removal of the device after 3 months of treatment, if necessary. Monthly clinical evaluations were conducted until the completion of the treatment, and follow-up examinations were conducted regularly for up to 6 years. The overall treatment success rate was 66.7% (26 of 39 patients), with success rates of 62.5% for patients with prosthetic knee infections, 50% for those with prosthetic hip infections, and 78.9% for those with other device infections. Seventeen of the 28 (60.7%) patients who did not have any orthopedic material removed were cured. Eight patients stopped the treatment because of side effects, and one patient was not compliant. In three patients treatment failed because of the appearance of a resistant bacterium. Long-term oral ambulatory treatment with co-trimoxazole appears to be an effective alternative to the conventional medicosurgical treatment of chronic multidrug-resistant Staphylococcus-infected orthopedic implants which includes long-term intravenous antibiotic therapy combined with surgical debridement and removal of foreign material or its subsequent one- or two-stage replacement.

Administration, Oral↗

PubMed2004

Eradication of methicillin resistant Staphylococcus aureus by "ring fencing" of elective orthopaedic beds.

PROBLEM: Deep infection after joint arthroplasty can be catastrophic, leading to further surgery, loss of the prosthesis, disability, and risk of mortality. Twenty nine new cases of methicillin resistant Staphylococcus aureus occurred in the first year after elective orthopaedic surgery was centralised to a district general hospital in Essex. DESIGN: Prospective trial to establish whether ring fencing of elective orthopaedic beds and introduction of simple infection control measures has an effect on the rates of postoperative infections and number of patients treated. PARTICIPANTS AND SETTING: All patients undergoing primary hip or knee replacement in a district general hospital in Essex, England, between July 1999 and July 2001. MAIN MEASURES FOR IMPROVEMENT: Number of patients having joint replacement; number of all postoperative infections in the participant group; number of cases of methicillin resistant Staphylococcus aureus. STRATEGIES FOR CHANGE: Ring fencing of the elective orthopaedic ward and introduction of simple infection control measures. EFFECTS OF CHANGE: The incidence of all postoperative infections decreased from 43/417 to 15/488 (P < 0.0001), with no new cases of methicillin resistant Staphylococcus aureus. LESSONS LEARNT: The introduction of a ring fenced elective orthopaedic ward and simple infection control measures allowed 17% more patients to be treated and significantly reduced the incidence of all postoperative infections.

Arthroplasty, Replacement, Hip↗

PubMed2006

Emerging Staphylococcus species as new pathogens in implant infections.

The vast use of prosthetic materials in medicine over the last decades has been accompanied by the appearance of new opportunistic pathogens previously considered incapable of causing infections with significant morbidity and/or mortality. In this regard, the genus Staphylococcus enlisting numerous species usually characterized by a saprophytic habit covers a special role. Apart from Staphylococcus aureus and Staphylococcus epidermidis, well known for their large prevalence in implant-related infections, a number of further staphylococcal species are progressively being indicated for their pathogenic potential. The increasing attention on these opportunistic bacteria is due to an ever growing number of clinical reports, which is also deriving from a more accurate identification of these species with currently available techniques. This synopsis intends to offer an overview on recently emerging coagulase-negative staphylococci (CoNS) as well as coagulase-positive/-variable staphylococci exhibiting distinct traits of virulence, pathogenicity, and epidemiologic impact depending among others on the medical field, the type of prosthetic device and its anatomic location.

Communicable Diseases, Emerging↗