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Nucleoside-nucleotide mixture and its components and response to methicillin-resistant Staphylococcus aureus infection in mice.

The effects of a nucleoside-nucleotide mixture and its individual components on response to methicillin-resistant Staphylococcus aureus (MRSA) strain 8985N were studied in mice. BALB/c mice were fed a nucleic-acid-free 20% casein diet and intraperitoneally administered a nucleoside-nucleotide mixture, its individual components (inosine, GMP2Na, uridine, thymidine, cytidine), or saline for 30 days. On the 10th day of this treatment, the mice were inoculated intravenously with the viable MRSA organisms. By the 20th day after inoculation, mice in the saline group showed 33% survival, whereas mice in the nucleoside-nucleotide mixture group showed 75% survival. The survival rates in the inosine (62%), GMP2Na (57%), uridine (54%), cytidine (50%), and thymidine (46%) groups were not significantly different. The survival rates of the individual-component groups tended to be higher than that of the saline group, but this was not statistically different. Furthermore, there was a greater reduction in viable organism recovery in the spleen and kidney of the surviving mice in the component groups than in the saline group. However, the survival rates in the individual-component groups did not exceed that of the nucleoside-nucleotide mixture group. This study suggests that intraperitoneal administration of a nucleoside-nucleotide mixture appears to be important in producing a high survival rate after challenge with MRSA. The effect cannot be achieved with the specific components of the mixture administered individually.

Animals↗

The use of pulsed field gel electrophoresis to investigate the epidemiology of Staphylococcus aureus infection in commercial broiler flocks.

Pulsed field gel electrophoresis (PFGE) analysis of SmaI restriction patterns was used to type 109 isolates of Staphylococcus aureus collected from broiler farms and hatcheries in Northern Ireland. Forty-seven isolates from clinical conditions in broilers and 62 strains from hatcheries, were examined. The PFGE patterns demonstrated a similarity between 85% of strains from clinical sources and 71% of the hatchery isolates. The association of disease with the predominant strain type and presence of these same strains in the hatchery, indicates that the hatchery is a potential source of the infection for clinical broiler disease.

Animals↗

Trimethoprim-sulfamethoxazole compared with vancomycin for the treatment of Staphylococcus aureus infection.

OBJECTIVE: To compare trimethoprim-sulfamethoxazole (TMP-SMZ) and vancomycin regarding efficacy and safety in the therapy of serious Staphylococcus aureus infections. DESIGN: Randomized, double-blind comparative trial. SETTING: A tertiary-care hospital. PATIENTS: One hundred and one intravenous drug users hospitalized with S. aureus infection. MEASUREMENTS: Cure and failure rates; blood and wound cultures; minimum inhibitory and bactericidal concentrations; serum inhibitory and bactericidal titers; temperature; leukocyte count; durations of treatment and hospitalization; and toxicity. RESULTS: Of 228 intravenous drug users, 101 had S. aureus infection and were included in the efficacy analysis (43 received TMP-SMZ and 58 received vancomycin). Methicillin-resistant S. aureus (MRSA) accounted for 47% of S. aureus isolates, and 65% of patients were bacteremic. Infections were cured in 57 of 58 vancomycin recipients and in 37 of 43 TMP-SMZ recipients (P less than 0.02). Failure occurred mostly in patients with tricuspid valve endocarditis and only in those with infection caused by methicillin-sensitive S. aureus (MSSA). The mean duration of bacteremia was 6.7 days in TMP-SMZ recipients and 4.3 days in vancomycin recipients. Among 222 subjects hospitalized for at least 24 hours, toxicity rates were similar for TMP-SMZ (23%) and vancomycin (20%) recipients; nausea and vomiting were associated with TMP-SMZ and inflammation at the intravenous site was associated with vancomycin. Forty-four percent of TMP-SMZ recipients and 29% of vancomycin recipients experienced side effects in the efficacy cohort (P greater than 0.05). CONCLUSIONS: Vancomycin is superior to TMP-SMZ in efficacy and safety when treating intravenous drug users who have staphylococcal infections. However, all treatment failures occurred in patients with MSSA infection at any site. Therefore, TMP-SMZ may be considered as an alternative to vancomycin in selected cases of MRSA infection.

Adult↗

Extracellular proteins as a potential marker of active Staphylococcus aureus infection in bone.

The potential of extracellular protein antigens of Staphylococcus aureus as markers of infection of bone was investigated by immunoblotting. Serum from patients with S. aureus bone infection showed levels of IgG antibodies to a preparation of soluble extracellular proteins of 17-81 kDa which were significantly higher than those found in serum from normal controls. By contrast, immunoblots of various whole cell or cell wall-derived antigens gave complex patterns of response which were unsuitable for positive diagnosis of S. aureus bone infection.

Antibodies, Bacterial↗

Emerging epidemic of community-acquired methicillin-resistant Staphylococcus aureus infection in the Northern Territory.

OBJECTIVE: To investigate the epidemiology of WA MRSA (the recently recognised Western Australian strains of methicillin-resistant Staphylococcus aureus) in the north of the Northern Territory (NT). DESIGN: Retrospective survey of data from hospital records. SETTING: Royal Darwin Hospital (a tertiary referral hospital that serves the north of the NT) between January 1991 and July 1995. SUBJECTS: All inpatients with clinical MRSA infection. OUTCOME MEASURES: Incidence of MRSA infection, classification of MRSA as WA or EA (Eastern Australian) based on antibiotic susceptibility, patient demographic details (age, sex, ethnicity, region of residence), source of infection (nosocomial or community-acquired). RESULTS: There were 125 WA MRSA and 93 EA MRSA infections, comprising 7% of all S. aureus infections. The incidence of WA MRSA infections consistently increased, while that of EA MRSA initially fell and then increased. All EA MRSA infections were nosocomial, while 50% of WA MRSA infections were community-acquired. Rates of WA MRSA infections were highest in patients from the west region of the NT, adjacent to the Kimberley region of Western Australia (WA). Community-acquired WA MRSA infections were more likely to affect Aboriginals than non-Aboriginals (relative risk [RR], 25.86; 95% confidence interval [CI], 12.51-53.47, based on population data; RR, 15.43; 95% CI, 7.85-30.32, based on admission data), as were nosocomial EA MRSA infections (RR, 2.54; 95% CI, 1.44-4.47, based on population data; RR, 2.30; 95% CI, 1.52-3.46, based on admission data). CONCLUSIONS: Changes in the epidemiology of MRSA infection in the north of the NT are consistent with the hypothesis that community-acquired WA MRSA spread into and across the NT from the Kimberley region of WA. Alternatively, crowded living conditions, hygiene difficulties and increasing use of broad spectrum antibiotics may have led to independent emergence of WA MRSA in both regions. Current infection control policies and their use in rural Aboriginal communities must be reassessed.

Adolescent↗

Activity of glycopeptides against Staphylococcus aureus infection in a rabbit endocarditis model: MICs do not predict in vivo efficacy.

The in vivo efficacy of vancomycin and teicoplanin against five Staphylococcus aureus strains with different susceptibilities to them and methicillin was studied. Rabbits were allocated at random to groups for endocarditis induction with one of these five strains and then treated for 2 days with vancomycin or teicoplanin. Each treated group was compared with a control group infected with the same strain. Vancomycin and teicoplanin showed similar activities. Low MICs did not predict better in vivo results.

Animals↗

Timentin therapy for Staphylococcus aureus infections in children: results of a multicenter trial.

Multicenter trials of ticarcillin/potassium clavulanate (Timentin) for bone, joint, skin and soft tissue infections in children were performed from 1983 to 1986. Fifty children with culture-confirmed Staphylococcus aureus infections were identified. Sixteen children (ages 6.2 +/- 3.9 years) with bone and joint infections received Timentin for 8.7 +/- 2.4 days with 11 of 16 cures, 5 of 16 improved, 11 of 11 bacteriologic cures and 3.9 +/- 3.5 days of fever. Thirty-two children (ages 5.7 +/- 3.5 years) with skin and soft tissue infections received Timentin for 5.3 +/- 1.6 days with 22 of 32 cures, 10 of 32 improved, 32 of 32 bacteriologic cures and 1.4 +/- 1.3 days of fever. Three patients had S. aureus bacteremia; all were clinical and bacteriologic cures. All S. aureus isolates were susceptible to Timentin, 18 of 23 isolates tested produced beta-lactamase and 21 of 44 isolates tested were resistant to ticarcillin. The purpose of this report is to describe the clinical efficacy of Timentin in treating these types of S. aureus infections in children.

Child↗

Central line perforation associated with Staphylococcus epidermidis infection.

We present detailed case reviews of four very low birth weight (VLBW) infants in whom central venous silastic catheter perforation was associated with Staphylococcus epidermidis sepsis. The diagnostic and therapeutic dilemma presented by the intracavitary fluid collections occurring in all four of these cases proved to be of clinical interest. Additionally, we propose a model that may account for the etiology of catheter displacement--localized phlebitis as a result of S epidermidis infection with resultant extralumenal migration of the central venous catheter.

Algorithms↗

The in-vivo activity of co-amoxiclav with netilmicin against experimental methicillin and gentamicin resistant Staphylococcus epidermidis infection in rabbits.

This study compared co-amoxiclav, vancomycin and teicoplanin with and without netilmicin or amikacin for treating experimental subcutaneous fibrin-clot infection in rabbits due to a clinical beta-lactamase-positive methicillin- and gentamicin-resistant Staphylococcus epidermidis strain (MGRSE). MICs (mg/L) for this strain were: oxacillin 125, gentamicin 32, vancomycin 4, teicoplanin 8, netilmicin 1, amikacin 4, amoxycillin 64 with clavulanate at 2 mg/L. In rabbits treated with a single-dose i.v. regimen (netilmicin 8 mg/kg, amikacin 20 mg/kg, vancomycin 30 mg/kg, teicoplanin 15 mg/kg, co-amoxiclav 150-30 mg/kg), the bacterial count 24 h post-dose was reduced whatever the combination used (ANOVA, P < or = 0.001). Regimens were statistically classified in decreasing order of efficacy as follows: co-amoxiclav combined with netilmicin > vancomycin either alone or combined with either netilmicin or amikacin, teicoplanin with netilmicin > netilmicin and co-amoxiclav alone > teicoplanin or co-amoxiclav combined with amikacin, and teicoplanin alone > amikacin > no drug. From these findings, it is concluded that: co-amoxiclav could be useful for the treatment of beta-lactamase-positive and methicillin-resistant S. epidermidis infection; some enzyme-resistant aminoglycoside could be considered for treating gentamicin-resistant but netilmicin/amikacin-sensitive S. epidermidis infection; the combination of co-amoxiclav with netilmicin was synergistic and more rapidly bactericidal than vancomycin in this animal model.

Amoxicillin↗

Staphylococcus aureus infections during peritoneal dialysis.

Peritoneal dialysis is in widespread use for the treatment of chronic renal failure. Infection is still one of the major complications and can include peritonitis and pericannular problems. The rate of peritonitis is currently 0.5 episodes per patient year with disconnect systems, and there are about 0.4 exit-site infections (ESIs) per patient year. ESI is associated with a high rate of catheter removal and replacement. Staphylococcus aureus is a common cause of peritonitis and accounts for more than half of all ESIs. Nasal carriage of S. aureus is associated with a much higher rate of ESI. Treatment of ESIs is unsatisfactory. The type of exit-site care, however, does influence the rate of infection and prophylaxis with oral rifampicin and local or nasal mupirocin has been claimed to reduce ESIs. A large multicentre double-blind trial of nasal mupirocin has just been completed and preliminary results show a reduction in the incidence of S. aureus-induced ESI. The cost benefits of such a regimen are being evaluated.

Humans↗

Rifampin resistance. Development during the therapy of methicillin-resistant Staphylococcus aureus infection.

The incidence of methicillin-resistant staphylococcal infections, for which vancomycin hydrochloride remains the only active cell-wall antibiotic therapy, is rising. Some physicians have been combining other antibiotics with vancomycin in hopes of obtaining a more effective regimen for the therapy of these infections. Rifampin has been advocated as a concurrent second antibiotic because of its extraordinary potent bactericidal activity for Staphylococcus aureus. When rifampin is used in combination with a cell-wall antibiotic, suppression of the development of rifampin resistance has been thought possible. We report a case of infection caused by a methicillin-resistant S aureus in which the rifampin resistance occurred during therapy with vancomycin and rifampin. The rifampin resistance was stable and was present after ten serial broth and agar passages. Physicians are cautioned against the indiscriminant or routine use of rifampin as a second antibiotic in combination with vancomycin for the therapy of infections caused by S aureus.

Adult↗

[Effects of a controlled Staphylococcus aureus infection on the renewal of endoalveolar cells].

We have studied, in rats, the influence of the intratracheal injection of 30 X 10(6) Staphylococcus aureus upon the differential count and renewal of the cell populations extracted by pulmonary lavage. In vivo labelling of alveolar macrophages was performed by intratracheal injection of 125I iododeoxyuridine, and the evolution of the labelled population was quantitatively followed up after scheduled sacrifice. Dividing cells were also identified at all times in the lavage population, after incorporation of (3H)-thymidine in vitro and autoradiography. The injection of Staphylococcus aureus induced an acute inflammatory process followed by the migration of polymorphonuclears, lymphocytes and macrophages mainly during the first 24 hours. Later on, no viable bacteria were observed and the cell populations returned to control values. Kinetic parameters were found varying as a function of the cell type. The early increase of macrophages was mainly produced by the migration of monocytes, which exhibited a shorter lifespan in alveolus than did resident macrophages. The inflammatory reaction observed, whilst inducing a considerable modification of the cell distributions, did not significantly modify the lifespan of macrophages located within alveolus before the aggression.

Animals↗

Staphylococcus aureus infections in injection drug users: risk factors and prevention strategies.

Infections, in particular soft tissue infections (cellulitis, skin abscesses), are the leading cause for emergency department visits and hospital admissions of drug injection users (IDUs). Staphylococcus aureus is the most relevant bacterial pathogen in this population. It is the main cause of soft tissue infections and of severe infections such as endocarditis and bacteremia. Moreover, epidemic spread of methicillin-resistant S. aureus (MRSA) among IDUs has occurred in Europe and North America. Nasal carriage of S. aureus is associated with an increased risk of subsequent S. aureus infections, and it has been shown that active IDUs have a higher rate of colonization with S. aureus than the general population. However, it is still unknown why an individual carries S. aureus. In particular, repeated injections do not appear to be the main predisposing factor for S. aureus carriage. Infections associated with injection drug use are frequently the consequence of the illegal status of street drugs. Harm reduction programs, including needle exchange programs, safer injecting facilities and injection opiate substitution programs can reduce the incidence of infections among severely addicted IDUs.

Humans↗

Severe Staphylococcus aureus infections caused by clonally related community-acquired methicillin-susceptible and methicillin-resistant isolates.

We investigated the genetic relatedness of 5 community-acquired (CA) Staphylococcus aureus isolates obtained from 4 consecutive pediatric patients presenting with sepsis syndrome and severe pneumonia during a 3-week period in 2000. Two patients were infected with methicillin-susceptible S. aureus (MSSA), and 2 were infected with methicillin-resistant S. aureus (MRSA). The pulsed-field gel electrophoresis patterns for the 2 CA-MRSA isolates were identical to each other, as were the patterns for the 3 CA-MSSA isolates. A 2-band difference reflecting the presence of a staphylococcal cassette chromosome mec (SCCmec) element distinguished the CA-MRSA isolates from the CA-MSSA isolates. The small, mobile type IV SCCmec element was present in the CA-MRSA isolates. These data suggest that an insertion or, less likely, a deletion of the SCCmec type IV element occurred in a highly virulent S. aureus background. Staphylococcal toxin genes sea, seh, lukS-PV, and lukF-PV were detected in all isolates. Also, in all isolates, was a partial homolog of seo (seo'). The relationship among these patient isolates strengthens the assumption that CA-MRSA infections may be caused by isolates closely related to MSSA isolates.

Adolescent↗