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Studies on clinical isolates of coagulase-negative staphylococci resistant to methicillin. Evidence of cross-resistance between methicillin and cephalothin.

The in vitro susceptibility to cephalothin and cefuroxime of 195 isolates of methicillin-resistant coagulase-negative staphylococci was determined by the agar-diffusion test, using 7.5% NaCl-supplemented agar. The distribution of the inhibition zone diameters for isolates of S. epidermidis (S. biotype 1) as well as for S. haemolyticus (S. biotype 4) was trimodal. While 4% of the isolates were found susceptible to cefuroxime, 39% of the S. epidermidis/S. hominis (S. biotype 1) isolates and 34% of the S. haemolyticus (S. biotype 4) isolates were found susceptible to cephalothin by this method. Eight of these isolates (six S. epidermidis, two S. haemolyticus) were selected for susceptibility testing by the tube-dilution method, together with four isolates (three S. haemolyticus, one S. epidermidis) found resistant to cephalothin by the agar-diffusion test. The first-mentioned isolates were all found susceptible to cephalothin with MICs less than or equal to 2 micrograms/l, while the last-named all were resistant with MICs greater than or equal to 16 micrograms/ml. Population analyses revealed sub-populations of highly resistant bacteria in all methicillin-resistant isolates of S. epidermidis (S. biotype 1), as well as in all isolates of S. haemolyticus (S. biotype 4). We thus concluded that methicillin-resistance in isolates of coagulase-negative staphylococci implies resistance to cephalosporins and that the difference between S. epidermidis and S. haemolyticus as regards cephalosporin-susceptibility is quantitative and not qualitative. Eighty-nine per cent of the 195 methicillin-resistant isolates in this study were resistant to penicillin and at least one more antibiotic. We therefore think that resistance to penicillin and one or more non-beta-lactam antibiotics strongly suggests methicillin-resistance and that such isolates should be further tested on hypertonic media.

Anti-Bacterial Agents↗

In vitro activities of rifapentine and rifampin, alone and in combination with six other antibiotics, against methicillin-susceptible and methicillin-resistant staphylococci of different species.

The antistaphylococcal activity of rifapentine, a new rifamycin SV derivative, was evaluated in vitro and compared with that of rifampin. A total of 313 staphylococcal strains freshly isolated from clinical material and including representatives of all currently recognized Staphylococcus species of human origin were used. The susceptibility to methicillin of all the test strains was determined preliminarily. Despite minor differences with some species, the MICs of rifapentine were found to be substantially similar to those of rifampin. Methicillin-resistant strains of all species were most resistant to rifapentine and rifampin than were their methicillin-susceptible counterparts. For most strains tested, the MBCs of both rifamycins exceeded by twofold the respective MICs. Both the checkerboard dilution and time-kill methods were used to determine the interactions of rifapentine or rifampin with six different antibiotics: cefamandole, vancomycin, teicoplanin, gentamicin, erythromycin, and fusidic acid. No significant differences between the two rifamycins in the combinations were observed against either methicillin-susceptible or methicillin-resistant strains. Minor differences were noted depending on the second antibiotic tested or the staphylococcal species examined. Antagonism was never observed, and indifference was the prevalent response. Cases of synergism were observed occasionally with the checkerboard method and slightly more often with the time-kill method.

Anti-Bacterial Agents↗

Pefloxacin therapy for experimental endocarditis caused by methicillin-susceptible or methicillin-resistant strains of Staphylococcus aureus.

The therapeutic efficacy of pefloxacin in experimental endocarditis caused by methicillin-susceptible or methicillin-resistant Staphylococcus aureus was evaluated. In rabbits infected with a methicillin-susceptible strain, 4 days of pefloxacin therapy significantly reduced both the number of bacteria per gram of vegetation and the mortality rate compared with untreated controls, and pefloxacin was equivalent to cephalothin. Pefloxacin was also as effective as vancomycin in reducing vegetation titers and mortality rate in animals with endocarditis caused by a methicillin-resistant strain. These results suggest that pefloxacin may be an effective agent in the therapy of serious infections caused by either methicillin-susceptible or -resistant strains of S. aureus.

Animals↗

Polycationic peptides as prophylactic agents against methicillin-susceptible or methicillin-resistant Staphylococcus epidermidis vascular graft infection.

Several polycationic peptides isolated from animals, plants, and bacterial species possess a broad spectrum of antimicrobial activity. A rat model was used to investigate the efficacies of two peptides, ranalexin and buforin II, in the prevention of vascular prosthetic graft infections. The effect of peptide-soaked collagen-sealed Dacron was compared to that of rifampin-soaked collagen-sealed Dacron in the rat model of graft infection caused by methicillin-susceptible rifampin-susceptible Staphylococcus epidermidis and methicillin-resistant rifampin-susceptible S. epidermidis. Graft infections were established in the back subcutaneous tissue of 240 adult male Wistar rats by implantation of 1-cm(2) Dacron prostheses, followed by topical inoculation with 2 x 10(7) CFU of S. epidermidis. The study included a control group (no graft contamination), two contaminated groups that did not receive any antibiotic prophylaxis, two contaminated groups to which perioperative intraperitoneal cefazolin prophylaxis (30 mg/kg of body weight) was administered, six contaminated groups that received a peptide- or rifampin-soaked graft, and six contaminated groups that received a peptide- or rifampin-soaked graft and perioperative intraperitoneal cefazolin prophylaxis (30 mg/kg). The grafts were sterilely removed 7 days after implantation, and the infection was evaluated by using sonication and quantitative agar culture. Overall, the efficacies of the polycationic peptides against the methicillin-susceptible and methicillin-resistant strains were not significantly different from that of rifampin. Nevertheless, the combinations of ranalexin- and buforin II-coated grafts with cefazolin treatment demonstrated efficacies significantly higher than that of the combination of rifampin-coated grafts and cefazolin treatment against the methicillin-resistant strain.

Animals↗

Genetic organization of the mecA region in methicillin-susceptible and methicillin-resistant strains of Staphylococcus sciuri.

A homolog of the Staphylococcus aureus methicillin resistance gene mecA was recently shown to be ubiquitous in independent isolates of the animal species Staphylococcus sciuri. The mecA gene homolog and regions flanking it were cloned and sequenced from four strains of S. sciuri: strain K1 (ATCC 29062), a representative of S. sciuri subsp. sciuri; two strains (K3 and K8) representing S. sciuri subsp. rodentius; and strain K11, a representative of S. sciuri subsp. carnaticum. Strains K1 and K11 were susceptible to methicillin, while strains K3 and K8 showed heterogeneous resistance. The mecA genes of strains K1 and K11 and one of the two copies of mecA (mecA1) present in strain K3 had virtually identical DNA sequences in the mecA gene and were similar in genetic organization in the flanking regions. In contrast, the single copy of mecA in strain K8 and the second copy of mecA (mecA2) in strain K3 had mecA DNA sequences identical to that of S. aureus mecA, and the mecA region in these two strains was also similar to that of the same region in the S. aureus strain used for comparison. Interestingly, an open reading frame defining an N-terminal truncated polypeptide, NTORF101, with a high degree of homology to a DNA segment in the hypervariable region of methicillin-resistant S. aureus (and also similar to the Escherichia coli gene ugpQ) was also identified downstream of the mecA homolog of strain K11, representing S. sciuri subsp. carnaticum. The ugpQ-like gene is not present in methicillin-susceptible strains of S. aureus. The presence of such a ugpQ-like gene together with the homolog of mecA in strain K11 supports the speculation that these genetic elements may be evolutionary relatives and/or precursors of the genetic determinant of methicillin resistance in S. aureus.

Amino Acid Sequence↗

Interlaboratory variation of antibiograms of methicillin-resistant and methicillin-susceptible Staphylococcus aureus strains with conventional and commercial testing systems.

Laboratory-prepared (conventional) and commercial susceptibility testing systems were compared by using a group of methicillin-resistant (MR) and methicillin-susceptible (MS) strains of Staphylococcus aureus. A group of 25 MR and 15 MS S. aureus strains were coded and tested blindly by disk diffusion, agar dilution, broth microdilution, Sensititre, Micro-Media, Sceptor, API 3600S, MicroScan, Autobac I, and MS-2 systems. All systems were incubated at 35 degrees C and read with either a manual or automated reader at the recommended times. Where applicable, systems were also read at 48 h. Among the conventional assays, the broth and agar dilution methods were comparable, both detecting 88% of the MR strains at 24 h and detecting 92 and 96%, respectively, at 48 h. The disk diffusion method was less efficient, detecting only 36 and 72% at 24 and 48 h, respectively. Detection of cephalothin resistance was low for all systems at both time periods, with agar dilution and disk diffusion being the most and least efficient, respectively. Some variability was also seen with detection of resistance to clindamycin and gentamicin. Among the MS strains, variability among the conventional systems occurred with methicillin, gentamicin, ampicillin, and penicillin. Comparison of the commercial systems with manual readers with the broth microdilution method (reference method) showed that for MR strains, the Sceptor system gave identical results at 24 and 48 h. Sensititre detected 68 and 88% of the MR strains, whereas Micro-Media was least effective detecting 12 and 80% at 24 and 48 h, respectively. None of the commercial systems detected cephalothin resistance well, with only one strain being indicated by the Sceptor and Sensititre systems at 48 h. Slight differences were also seen among the systems with clindamycin and gentamicin. With regard to the MS strains, variability among the systems was seen with methicillin, penicillin, ampicillin, clindamycin, and gentamicin. Among commercial systems with automated readers, the API system detected a greater number of MR strains than did the reference method at 24 and 48 h, 96 and 100%, respectively. The MicroScan method was comparable to the reference method detecting 80 and 88% of the MR strains at both time periods, respectively. Both Autobac I and MS-2 were much less effective in detecting MR strains, noting only 32 and 16%, respectively, at the 3- to 6-h readings. Poor detection of cephalothin resistance among MR strains was evident in all systems. Variability also occurred among the systems with clindamycin, gentamicin, and ampicillin. A single strain of the MR group was reported to be vancomycin resistant by the API system. Among the MS group, the greatest variability was seen with methicillin. Less variability occurred with penicillin, ampicillin, gentamicin, and vancomycin.

Humans↗

Distribution of a methicillin-resistance gene in urinary isolates of methicillin-resistant staphylococci examined by enzymatic detection of the polymerase chain reaction.

We tried to examine the susceptibility to various antimicrobial agents and to detect the mec A gene using enzymatic detection of the polymerase chain reaction in methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive Staphylococcus aureus (MSSA) and Staphylococcus epidermidis isolated from patients with complicated urinary tract infections (UTIs). All the strains of MRSA and MSSA showed a low sensitivity to imipenem (IPM), ceftazidime (CAZ), flomoxef (FMOX), amikacin (AMK), ciprofloxacin (CPFX) and ofloxacin (OFLX). Although all the strains of MRSA had the mec A gene, none of the MSSA strains had it. 74% of S. epidermidis had the mec A gene and strains resistant to methicillin were seen in 72% of them. The mec A-positive S. epidermidis showed a lower susceptibility to IPM, CAZ, FMOX, AMK, CPFX and OFLX than the mec A-negative strains. These results suggest that methicillin resistance was due to the mec A gene in MRSA and methicillin-resistant S. epidermidis (MRSE), and that MRSEs were very common among the bacteria causing complicated UTI. When we try to control nosocomial infections due to MRSA, it should also be noted that MRSE can be a reservoir of the mec A gene.

Genes, Bacterial↗

Comparative in vitro activity of quinupristin/dalfopristin and seven other antimicrobials against methicillin-susceptible and methicillin-resistant nosocomial Staphylococcus aureus bloodstream isolates.

Staphylococcus aureus strains resistant to a variety of antimicrobial agents are often found in the hospital environment and are responsible for many life-threatening infections. The activity of quinupristin/dalfopristin against 84 Staphylococcus aureus bloodstream isolates (both methicillin resistant and methicillin sensitive) was compared to the activity of vancomycin, teicoplanin, erythromycin, oxacillin, clindamycin, gentamicin, rifampicin. The Minimum Inhibitory Concentrations of these agents was evaluated with the Epsilometer Test. Quinupristin/dalfopristin inhibited all methicillin-sensitive strains at 1mg/L, and 75% of methicillin-resistant strains at 1.5mg/L. According to these results, quinupristin-dalfopristin shows promising in-vitro activity and may be a welcome alternative treatment for methicillin-resistant staphylococcal infections, resulting in reduced use of glycopeptides.

Anti-Bacterial Agents↗

Effect of methicillin on the fatty acid composition of phospholipids in methicillin sensitive Staphylococcus aureus.

The effect of two concentrations of methicillin on the distribution of fatty acid (FA) in the individual phospholipids of the middle-log phase cultures of Staphylococcus aureus 5814S sensitive to methicillin was studied during a period of 2 h. In the presence of 1/2 X minimum inhibitory concentration (MIC) of methicillin (= 1 microgram/ml) the ratio of unsaturated fatty acid (UFA) + branched fatty acid (BFA) to saturated fatty acid (SFA) in the phosphatidic acid (PA) and in the C55-isoprenylphosphate (C55-IP) became significantly higher due mainly to the accumulation of n-C12 : 3, ai-C17 : 0, and ai-C19 : 0, and to the fall of n-C14 : 0, n-C16 : 0, and n-C20 : 0 in the PA, and to the 3-fold increase in n-C12 : 3 and a 2-fold decrease in the SFAs of the C55-IP. In contrast, the ratio of UFA + BFA to SFA was smaller in the phosphatidylglycerol (PG) and lysylphosphatidylglycerol (LPG) than that of the control. The reduction was attributed to a loss of ai-C15 : 0 and a gain of n-C20 : 0 in the PG, and to the decrease in ai-C17 : 0 and to the increase in n-C20 : 0 in the LPG. On the whole, the fluidity of the membrane phospholipids decreased. In the presence of 1 X MIC of methicillin (= 2 micrograms/ml) the ratio of UFA + BFA to SFA became higher in the PA due mainly to the prevention of the release of n-C18 : 1. In all the other phospholipids the ratio of UFA + BFA to SFA was smaller than in the control of the same age. The decrease in the ratios ranged in the order of C55-IP, PG, diphosphatidylglycerol (DPG) and LPG. The changes were attributed to the decrease in the proportion of n-C12 : 3 and ai-C15 : 0 or ai-C17, and to the increase in n-C20 : 0, except DPG. Thus the membranes in methicillin treated cocci were significantly less fluid than in the controls.

Cardiolipins↗

Effect of methicillin on the phospholipid content of methicillin sensitive Staphylococcus aureus.

The effects of methicillin at concentrations of 1 microgram/ml (= 1/2 x minimum inhibitory concentration) and 2 microgram/ml (= 1 x MIC) on the phospholipid content of methicillin-sensitive Staphylococcus aureus 5814S growing exponentially were studied. During 2-hour treatment 1/2 x MIC of methicillin induced a significant increase in the phospholipid content of the cocci; accumulation of acid phospholipids was prevalent. In contrast, addition of 1 x MIC of methicillin to the cultures resulted in significantly less phospholipids in the cocci compared with that of the control cultures. There were some alterations in the amounts of individual phospholipids during treatment. The phosphatidic acid (PA) and diphosphatidylglycerol--cardiolipin (DPG) contents were significantly reduced in the first hour then reached the control values by the end of the 2nd hr of exposure. An opposite change was found in the amount of lysylphosphatidylglycerol (LPG), whereas the phosphatidylglycerol (PG) level was significantly lower in the treated cultures than in the controls of corresponding age. Phospholipid synthesis seems to be one of the sites of the action of methicillin in S. aureus.

Cardiolipins↗

Comparison of the bactericidal activities and post-antibiotic effects of the Des-F(6)-quinolone BMS-284756, levofloxacin, and ciprofloxacin against methicillin-susceptible and methicillin-resistant Staphylococcus aureus.

The bactericidal activities and post-antibiotic effects of BMS-284756 (T-3811ME), levofloxacin, and ciprofloxacin were evaluated against a methicillin-susceptible and a methicillin-resistant Staphylococcus aureus strain. Minimum inhibitory concentrations (MICs), minimum bactericidal concentrations, post-antibiotic effects, and post-antibiotic sub-MIC effects were determined and time-kill studies were performed for BMS-284756, levofloxacin, and ciprofloxacin. At 4-times and 10-times the MIC, time-kill kinetics over 3 h and over 24 h were similar for all three quinolones when effects were considered as multiples of the MIC. All three quinolones achieved a 3 log10 reduction in cfu/ml within 2 h. At 10-times the MIC, the post-antibiotic effects of BMS-284756, levofloxacin, and ciprofloxacin were 1.6-2.6 h for the methicillin-susceptible Staphylococcus aureus strain and 1.5-1.9 h for the methicillin-resistant Staphylococcus aureus strain. When actual concentrations were considered, BMS-284756 achieved results comparable to levofloxacin and ciprofloxacin at concentrations nearly 10-fold less. When relating the pharmacokinetic properties of the three quinolones to their in vitro activities, the resulting Cmax/MIC and AUC/MIC ratios were. respectively, 120-240.7 and 1,321.7-2,643 for BMS-284756, 22.8 and 190 for levofloxacin, and 5.9-11.9 and 54.8-109.6 for ciprofloxacin. The greater in vitro activity and favorable human pharmacokinetics of BMS-284756 may translate to improved clinical effectiveness of this agent compared to currently marketed quinolones.

Anti-Infective Agents↗

Costs and outcomes among hemodialysis-dependent patients with methicillin-resistant or methicillin-susceptible Staphylococcus aureus bacteremia.

OBJECTIVE: Comorbid conditions have complicated previous analyses of the consequences of methicillin resistance for costs and outcomes of Staphylococcus aureus bacteremia. We compared costs and outcomes of methicillin resistance in patients with S. aureus bacteremia and a single chronic condition. DESIGN, SETTING, AND PATIENTS: We conducted a prospective cohort study of hemodialysis-dependent patients with end-stage renal disease and S. aureus bacteremia hospitalized between July 1996 and August 2001. We used propensity scores to reduce bias when comparing patients with methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) S. aureus bacteremia. Outcome measures were resource use, direct medical costs, and clinical outcomes at 12 weeks after initial hospitalization. RESULTS: Fifty-four patients (37.8%) had MRSA and 89 patients (62.2%) had MSSA. Compared with patients with MSSA bacteremia, patients with MRSA bacteremia were more likely to have acquired the infection while hospitalized for another condition (27.8% vs 12.4%; P = .02). To attribute all inpatient costs to S. aureus bacteremia, we limited the analysis to 105 patients admitted for suspected S. aureus bacteremia from a community setting. Adjusted costs were higher for MRSA bacteremia for the initial hospitalization (21,251 dollars vs 13,978 dollars; P = .012) and after 12 weeks (25,518 dollars vs 17,354 dollars; P = .015). At 12 weeks, patients with MRSA bacteremia were more likely to die (adjusted odds ratio, 5.4; 95% confidence interval, 1.5 to 18.7) than were patients with MSSA bacteremia. CONCLUSIONS: Community-dwelling, hemodialysis-dependent patients hospitalized with MRSA bacteremia face a higher mortality risk, longer hospital stays, and higher inpatient costs than do patients with MSSA bacteremia.

APACHE↗

Methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis infections in the cornea.

PURPOSE: To describe the incidence and clinical management of corneal infections with methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant Staphylococcus epidermidis (MRSE). METHODS: The incidence of methicillin-resistant Staphylococcus (MRS) at the Department of Ophthalmology, Kyoto Prefectural University of Medicine, was reviewed during the 5-year period from January 1996 to December 2000. Clinical aspects of MRS colonization or infection in the eye were investigated. RESULTS: Methicillin-resistant S. aureus or MRSE was detected from 30 eyes with ocular diseases; post-keratoplasty (11 eyes), ocular surface disorders without operation (9 eyes), and others (10 eyes). Among the 30 eyes, 12 manifested keratitis. Eight cases (8 eyes) occurred after keratoplasty, including four postoperative cases in patients with Stevens-Johnson syndrome, and two bilateral cases (4 eyes) in patients with acute-phase Stevens-Johnson syndrome. The degree of MRS keratitis was classified into 4 groups: asymptomatic carrier or conjunctivitis, intraepithelial infiltrations, superficial keratitis, and severe keratitis leading to corneal perforation. All cases of keratitis were treated successfully with topical ofloxacin (OFLX), vancomycin (VCM), or arbekacin (ABK). CONCLUSION: Factors associated with ocular MRS colonization were long-term use of antibiotics and/or steroids, and hospitalization. Patients who had undergone keratoplasty or who had Stevens-Johnson syndrome were at increased risk of MRS keratitis. Superficial stromal infiltrations, minimal melting, and minimal stromal scarring are characteristic of MRS keratitis. Therapy for MRS keratitis is summarized. Ofloxacin, VCM, and ABK are effective in the treatment of MRS keratitis. Vancomycin eye ointment is effective as the final choice in serious cases.

Adult↗

Identification in methicillin-susceptible Staphylococcus hominis of an active primordial mobile genetic element for the staphylococcal cassette chromosome mec of methicillin-resistant Staphylococcus aureus.

We previously reported that the methicillin resistance gene mecA is carried by a novel type of mobile genetic element, SCCmec (staphylococcal cassette chromosome mec), in the chromosome of methicillin-resistant Staphylococcus aureus (MRSA). These elements are precisely excised from the chromosome and integrated into a specific site on the recipient chromosome by a pair of recombinase proteins encoded by the cassette chromosome recombinase genes ccrA and ccrB. In the present work, we detected homologues of the ccr genes in Staphylococcus hominis type strain GIFU12263 (equivalent to ATCC 27844), which is susceptible to methicillin. Sequence determination revealed that the ccr homologues in S. hominis were type 1 ccr genes (ccrA1 and ccrB1) that were localized on a genetic element structurally very similar to SCCmec except for the absence of the methicillin-resistance gene, mecA. This genetic element had mosaic-like patterns of homology with extant SCCmec elements, and we designated it SCC(12263) and considered it a type I staphylococcal cassette chromosome (SCC). The ccrB1 gene identified in the S. hominis strain is the first type 1 ccrB gene discovered to retain its function through the excision process as judged by two criteria: (i) SCC(12263) was spontaneously excised during cultivation of the strain and (ii) introduction of the S. hominis ccrB1 into an MRSA strain carrying a type I SCCmec whose ccrB1 gene is inactive generated SCCmec excisants at a high frequency. The existence of an SCC without a mec determinant is indicative of a staphylococcal site-specific mobile genetic element that serves as a vehicle of transfer for various genetic markers between staphylococcal species.

Amino Acid Sequence↗

[Methicilline-sensitive and methicilline-resistant Staphylococcus aureus related morbidity in chronic wounds: a prospective study].

OBJECTIVE: Staphylococcus aureus is the most common bacteria responsible for cutaneous infections. Its capacity to adapt has led to the selection of methicilline-resistant strains (MRSA). These strains create specific problems in their management in dermatology (mode of contamination, treatment, added costs, increased nosocomial risks). The objective of our study was to search for morbidity of MRSA in chronic cutaneous wounds in hospital settings and assess the need of systemic antibiotic therapy. PATIENTS AND METHODS: We have conducted a one-year prospective study. All the patients hospitalized in the department with leg ulcers or foot wounds were included. Following local sampling for bacteriological examination, three groups were constituted: methicilline-sensitive patients with staphylococcus aureus (MSSA), methicilline-resistant staphylococcus aureus patients and patients in whom these bacteria were absent. Only the first two groups were compared after studying the past history, clinical description of the wound at the start of the study, results of the infectious bacteriology and of the clinical and bacteriological evolution of the wounds. RESULTS: The two groups studied were similar in number, past history, clinical aspect and therapeutic management. Only malnutrition was more frequent in patients exhibiting MRSA. There was no difference with the evolution of the wounds. CONCLUSION: Our study did not reveal any difference in the morbidity of staphylococcus aureus in the cutaneous wounds whether methicilline sensitive or resistant. Systematic antibiotherapy is not justified in the absence of signs of infection.

Adult↗

[Incidence of methicillin-resistant and methicillin-susceptible Staphylococcus strains in clinical materials].

365 S. aureus and 165 CNS were evaluated for susceptibility to methicillin. They were received from various clinic of Clinical Hospital in Bydgoszcz. The bacterial cells that grew in the presence of 25 mg methicillin/L were evaluated as methicillin-resistant. It was found that the 129 MRSA and MRCNS. Incidence depended on the kind of clinic and material. Most often they were isolated from clinic: Surgery, Neurosurgery, Intensive Care Unit, Neurology and Ortopedics. They were from: intubation tube, catheters and vascular grafts. The methicillin-resistant S. epidermidis and S. haemolyticus showed above 50% resistance to methicillin.

Blood Vessel Prosthesis↗

Outcome and attributable mortality in critically Ill patients with bacteremia involving methicillin-susceptible and methicillin-resistant Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus bacteremia carries high mortality rates. The clinical impact of methicillin resistance remains controversial: outcome comparisons between patients with bacteremia involving methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) S aureus are difficult to perform because of important differences in severity of illness. METHODS: A retrospective cohort analysis and 2 independent case-control analyses were performed to determine and compare outcomes and attributable mortality rates of MSSA (n = 38) and MRSA bacteremia (n = 47) in critically ill patients. For the case-control studies, matching (1:2 ratio) was based on the APACHE (Acute Physiology and Chronic Health Evaluation) II classification: APACHE II score (+/-1 point) and diagnostic category. RESULTS: Patients with MRSA bacteremia had more acute renal failure and hemodynamic instability than patients with MSSA bacteremia. They had a longer intensive care unit stay and ventilator dependency. Patients with MRSA bacteremia had a higher 30-day mortality rate (53.2% vs 18.4%) and in-hospital mortality rate (63.8% vs 23.7%) (P<.05). Multivariate survival analysis demonstrated acute renal failure, length of mechanical ventilation, age, and methicillin resistance to be independently associated with mortality (P<.05). The attributable mortality rate for MSSA bacteremia was 1.3%: mortality rates for cases and controls were respectively 23.7% and 22.4% (P =.94). The attributable mortality rate for MRSA bacteremia was 23.4%: mortality rates for cases and controls were respectively 63.8% and 40.4% (P =.02). The difference (22.1%) between both attributable mortality rates was significant (95% confidence interval, 8.8%-35.3%). CONCLUSION: In critically ill patients, after accurate adjustment for disease severity and acute illness, we found MRSA bacteremia to have a higher attributable mortality than MSSA bacteremia.

Acute Kidney Injury↗

Consecutive isolation of homologous strains of methicillin-resistant and methicillin-susceptible Staphylococcus aureus from a hospitalized child.

A multiply resistant, methicillin-resistant Staphylococcus aureus was repeatedly isolated from the anterior nares of a premature neonate hospitalized in an intensive-care unit and treated with multiple courses of antibiotics. Two months following cessation of antibiotic therapy, a strain of S. aureus with a similar antibiotic resistance profile, but susceptible to methicillin, was isolated from three consecutive nasal swabs. Total DNA of the methicillin-susceptible and -resistant isolates was digested with SmaI and resolved by pulsed-field gel electrophoresis. The SmaI restriction profile of the susceptible isolate was similar to that of the resistant one except for the replacement of a 207-kb fragment by a 147-kb fragment. In Southern hybridization, a mecA-specific probe hybridized to the 207-kb SmaI fragment of the methicillin-resistant strain but not to DNA of the susceptible strain. These results suggest that loss of the mecA gene can occur in vivo when antibiotic selective pressure is removed.

Base Sequence↗