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Freely accessible endoscope channels improve efficacy of cleaning.

BACKGROUND AND STUDY AIMS: Inadequate cleaning and disinfection of medical devices, including flexible endoscopes, can result in the transmission of micro-organisms to patients. The aim of this study was to investigate the influence of the design of medical devices on the efficacy of manual cleaning of endoscope channels. MATERIALS AND METHODS: The investigation was carried out using four endoscopes (two duodenoscopes and two gastroscopes). The air/water channels of one duodenoscope and one gastroscope were freely accessible and could be brushed. The instrumentation and the air/water channels were contaminated with blood containing Enterococcus faecium as a test organism. After manual cleaning of the channels by flushing and, where possible, brushing, the recovery rates for the test organism were studied. RESULTS: The comparable rates for recovery of the test organism after cleaning of the instrumentation channels proved that the method used was reproducible. With regard to the air/water channels, the rate of micro-organisms in the cleaning solution recovered after flushing alone was a maximum of 3 % relative to the rate detected after brushing and flushing. CONCLUSIONS: The data collected in the study show that only flushing channels that are not freely accessible resulted in significantly lower (P<0.001) recovery rates for the test organism. In practice, this means that contamination may remain in the channels, and it shows that the design of a medical device has an important influence on the reprocessing of reusable instruments such as flexible endoscopes.

Disinfection↗

[New treatment option for gram-positive infections in critically ill patients - overview over linezolid].

INTRODUCTION: During the last decade, there has been an emergence of multiresistant Gram-positive bacteria in intensive care units. Oxazolidinones are a new class of antibiotics without cross-resistance to other antimicrobial agents, and linezolid was recently introduced as first oxazolidinone on the German market. In this overview, we summarize important data and discuss possible indications for linezolid in the treatment of infections in critically ill patients. ANTIMICROBIAL ACTIVITY AND PHARMACOLOGY: The antimicrobial spectrum comprises mainly Gram-positive bacteria, especially Staphylococcus aureus (including MRSA), coagulase-negative staphylococci, enterococci, and streptococci. Linezolid is mostly bacteriostatic and inhibits the bacterial protein synthesis at an early stage. Adults may receive 600 mg b.i.d. intravenously or p. o. About 30 % of the dose are excreted by the kidneys as mother compound and 50 % as metabolites. Dosage reductions are not necessary, even in severe renal impairment, but about one third of the dose is eliminated during dialysis. Overall, linezolid is well tolerated, but approximately 5 % of the patients may suffer from diarrhea or nausea and there have been a few reports about reversible myelosuppressive side effects. CLINICAL STUDIES: Linezolid has been compared to vancomycin for treatment of Gram-positive nosocomial pneumonia, and the clinical cure rates were 66.4 % and 68.1 %, respectively. Linezolid is highly active and bactericidal against pneumococci. The clinical cure rates for treatment of skin and soft tissue infections were 88.1 % with linezolid and 86.1 % with penicillinase-stable penicillins. MRSA were excluded in this study, but it may be assumed from data in vitro that linezolid is equally effective against these bacteria. Data for the treatment of catheter-associated and other forms of bacteremias are mainly derived from the compassionate-use-program, where linezolid has been used in complicated cases, mainly after failure of standard therapy. The majority of infections was caused by multiresistant Enterococcus faecium and the clinical cure rates were approximately 80 %. COMMENT: The currently available data suggest that linezolid will serve as useful agent in the treatment of severe infections caused by multiresistant staphylococci and enterococci. Further studies are necessary to define the role of linezolid as first-line agent, e. g. in the treatment of central venous catheter infections. In light of the severe prognosis of pneumonias caused by MRSA, studies on the combination of linezolid and vancomycin are warranted. Despite the low level of resistance, it seems prudent not to use linezolid as first line agent in the treatment of uncomplicated infections, as long as effective standard antibiotics are available.

Acetamides↗

Antiviral activity of N-benzoylphenylisoserinates of Lactarius sesquiterpenoid alcohols in vitro.

Cytotoxic, antiviral, antibacterial and antifungal properties of a new, originally synthesised group of compounds: the N-benzoylphenylisoserinates of sesquiterpenoid alcohols - derivatives of taxol and various sesquiterpenes of Lactarius origin were evaluated in vitro. Among 16 compounds tested, 6 decreased HSV-1 titres. Selectivity indices ranged from 13.9 to 31.7. No activity against RNA viruses (parainfluenza 3, Coxsackie B3, vesicular stomatitis virus, and encephalomyocarditis virus), bacteria: Escherichia coli, Proteus mirabilis, Staphylococcus aureus, Enterococcus faecium and Bacteroides fragilis and fungal strain of Candida albicans was detected.

Agaricales↗

[Antibacterial effectiveness of high-energetic extracorporeal shock waves: an in vitro verification].

AIM: Extracorporeal shock wave therapy (ESWT) is used for a multitude of different indications in modern orthopedics. Local bacterial infections, like infected pseudarthrosis, are still considered as contraindications. The goal of the present study was to determine the effect of ESWT on the growth of clinically relevant bacteria in orthopedic and trauma surgery. METHODS: Standardized suspensions of five bacterial strains of bone and implant-associated infections were treated with 4 000 impulses of high-energy shock waves with an energy flux density (ED) of 0.96 mJ/mm (2) and a frequency of 2 Hz. Subsequently, viable bacteria were quantified and compared with an untreated control. RESULTS: A highly significant antibacterial effect of the ESWT was demonstrated for all bacterial strains with a reduction of growth to values between 1.1 % and 29.7 % (p < 0.01). Reference strains of Staphylococcus aureus and Staphylococcus epidermidis reacted with the highest sensitivity whereas Enterococcus faecium demonstrated the highest resistance towards high-energy shock waves. CONCLUSION: ESWT proved to exert a significant antibacterial effect on clinically relevant pathogens. Further investigations on energy flux density and impulse rates might contribute to an optimization of the bactericidal effectiveness. Infections as possible indications of the ESWT should therefore be assessed in further studies and the clinical relevance should be verified in an animal model.

Dose-Response Relationship, Radiation↗

[Bacteremia in intra-arterial angiography, percutaneous transluminal angioplasty and percutaneous transhepatic cholangio-drainage].

PURPOSE: Prospective evaluation of the rate of bacteremia attributed to invasive radiological techniques. METHODS: Aerobic and anerobic blood cultures were obtained in 100 patients (62 men, 38 women; mean age 65 +/- 14 years) undergoing intra-arterial angiography (N = 50), PTA (N = 30) or percutaneous transhepatic biliary drainage (PTCD; N = 20). Samples were taken before the treatment (T0), immediately after puncture of the vessel or bile duct (T2), and 30 min after the termination of the procedure (T3). RESULTS: The overall rate of bacteremia was 18%. During diagnostic angiography a 16% rate of temporary bacteremia (no positive T3 samples) was observed. During PTA the rate was 27% (no clinically significant infectious disease) and during PTCD the rate was 10% (5% cholangitis with septicemia). We isolated staphylococci (S. epidermidis: N = 7, S. species: N = 3, S. aureus: N = 1), streptococci (N = 2), Propionibacterium acnes (N = 5), E. coli (N = 1), Enterococcus faecium (N = 1), Enterobacter species (N = 1), and Clostridium perfringens (N = 1). Apart from the one patient with cholangitis no clinical infectious complication occurred. CONCLUSION: Temporary bacteremia is rather frequent during invasive radiological procedures. Strictly aseptic conditions and antibiotic prophylaxis, specially in case of implantation of a permanent foreign body, is warranted.

Aged↗

Persistent silver disinfectant for the environmental control of pathogenic bacteria.

BACKGROUND: Contaminated surfaces can act as a reservoir for pathogenic microorganisms and potentially exacerbate the risk of infection. Surface disinfection and decontamination provide temporary amelioration against bacterial colonization. Disinfected surfaces eventually become contaminated, thus, mitigating the benefit of the initial disinfection. It is hypothesized that to improve on the current state of the art, a disinfectant should not only immediately disinfect a surface but also provide persistent antimicrobial action after the product has been applied. We describe here a silver-based disinfectant technology designed to provide long-lasting sanitization and disinfection to treated surfaces as evaluated on hard surfaces after repeated environmental insults. METHODS: A comparative evaluation of 6 disinfectant formulations for residual antimicrobial activity after water rinsing was performed. Log reduction of bacterial populations on disinfectant-treated substrates were measured after 30 minutes to 8 hours of exposure and compared with an untreated control. In a similar study, the residual antimicrobial activity of a silver disinfectant was evaluated against antibiotic- and biocide-resistant bacteria also after water rinsing. Further, residual antimicrobial activity of the silver disinfectant was measured after 5 cycles of rinsing, abrasion, and contamination against representative household and nosocomial pathogens (Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Enterobacter aerogenes, Enterococcus faecium, or Salmonella choleraesuis) after 10-minute exposure times. RESULTS: In the comparative assay, only the silver disinfectant and a persistent quaternary ammonium compound disinfectant demonstrated significant residual activity (> or =3.0 log(10) reduction to control) against S aureus whereas only the silver disinfectant demonstrated activity against Pseudomonas. No residual activity (< or = 0.5 log reduction to untreated control) was observed for the other disinfectant products. The silver-based disinfectant also showed significant and equivalent efficacy against antibiotic- and silver-resistant bacteria. In addition, the silver disinfectant was able to achieve significant residual activity in 10 minutes against all organisms tested after 1, 3, and 5 cycles of water rinse, abrasion, and microbial contamination. CONCLUSIONS: The findings show the ability of a new silver-based disinfectant to reduce bacterial populations that contact treated surfaces within minutes, highlight the potential to interrupt cross-contamination from environmental surfaces, and reduce the risk of infection within the home and health care settings.

Bacteria↗

An in vitro study of antibacterial properties of the cervical mucus plug in pregnancy.

OBJECTIVE: To evaluate whether cervical mucus plugs are antibacterial in vitro. STUDY DESIGN: Cervical mucus plugs from 56 healthy women in labor were studied by 2 different antimicrobial assays: (1) analysis of the inhibition by the cervical mucus plug of several gram-positive and gram-negative bacteria by overlaying the cervical mucus plug onto an agar plate with imbedded bacteria, and (2) determination of the antibacterial property of the cervical mucus plug material by radial diffusion assay with group B Streptococcus and Escherichia coli. RESULTS: In the agar overlay assay, there was complete inhibition of clinical isolates of Staphylococcus saprophyticus, E coli, and Pseudomonas aeruginosa and patient-variable partial-to-complete inhibition of Enterococcus faecium, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus agalactiae. In the radial diffusion assay, cervical mucus plugs had activity toward group B Streptococcus equivalent to 0.075 microg/mL of gentamicin and toward E coli equivalent to 0.5 microg/mL of gentamicin. CONCLUSION: A low-molecular substance with antibacterial activity in the cervical mucus plug may protect the fetus against ascending infections.

Anti-Bacterial Agents↗

Complexation of peptidoglycan intermediates by the lipoglycodepsipeptide antibiotic ramoplanin: minimal structural requirements for intermolecular complexation and fibril formation.

The peptide antibiotic ramoplanin inhibits bacterial peptidoglycan (PG) biosynthesis by interrupting late-stage membrane-associated glycosyltransferase reactions catalyzed by the transglycosylase and MurG enzymes. The mechanism of ramoplanin involves sequestration of lipid-anchored PG biosynthesis intermediates, physically occluding these substrates from proper utilization by these enzymes. In this report, we describe the first molecular-level details of the interaction of ramoplanin with PG biosynthesis intermediates. NMR analysis in conjunction with chemical dissection of the PG monomer revealed that the ramoplanin octapeptide D-Hpg-D-Orn-D-alloThr-Hpg-D-Hpg-alloThr-Phe-D-Orn recognizes MurNAc-Ala-gamma-D-Glu pyrophosphate, the minimum component of PG capable of high-affinity complexation and fibril formation. Ramoplanin therefore recognizes a PG binding locus different from the N-acyl-D-Ala-D-Ala moiety targeted by vancomycin. Because ramoplanin is structurally less complex than glycopeptide antibiotics such as vancomycin, peptidomimetic chemotherapeutics derived from this recognition sequence may find future use as antibiotics against vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus, and related pathogens.

Amino Acid Sequence↗

Isolation and characterization of human beta -defensin-3, a novel human inducible peptide antibiotic.

The growing public health problem of infections caused by multiresistant Gram-positive bacteria, in particular Staphylococcus aureus, prompted us to screen human epithelia for endogenous S. aureus-killing factors. A novel 5-kDa, nonhemolytic antimicrobial peptide (human beta-defensin-3, hBD-3) was isolated from human lesional psoriatic scales and cloned from keratinocytes. hBD-3 demonstrated a salt-insensitive broad spectrum of potent antimicrobial activity against many potentially pathogenic microbes including multiresistant S. aureus and vancomycin-resistant Enterococcus faecium. Ultrastructural analyses of hBD-3-treated S. aureus revealed signs of cell wall perforation. Recombinant hBD-3 (expressed as a His-Tag-fusion protein in Escherichia coli) and chemically synthesized hBD-3 were indistinguishable from naturally occurring peptide with respect to their antimicrobial activity and biochemical properties. Investigation of different tissues revealed skin and tonsils to be major hBD-3 mRNA-expressing tissues. Molecular cloning and biochemical analyses of antimicrobial peptides in cell culture supernatants revealed keratinocytes and airway epithelial cells as cellular sources of hBD-3. Tumor necrosis factor alpha and contact with bacteria were found to induce hBD-3 mRNA expression. hBD-3 therefore might be important in the innate epithelial defense of infections by various microorganisms seen in skin and lung, such as cystic fibrosis.

Amino Acid Sequence↗

Characterisation of IS153, an IS3-family insertion sequence isolated from Lactobacillus sanfranciscensis and its use for strain differentiation.

An insertion sequence has been identified in the genome of Lactobacillus sanfranciscensis DSM 20451T as segment of 1351 nucleotides containing 37-bp imperfect terminal inverted repeats. The sequence of this element encodes two out of phase, overlapping open reading frames, orfA and orfB, from which three putative proteins are produced. OrfAB is a transframe protein produced by -1 translational frame shifting between orf A and orf B that is presumed to be the transposase. The large orfAB of this element encodes a 342 amino acid protein that displays similarities with transposases encoded by bacterial insertion sequences belonging to the IS3 family. In L. sanfranciscensis type strain DSM 20451T multiple truncated IS elements were identified. Inverse PCR was used to analyze target sites of four of these elements, but except of their highly AT rich character not any sequence specificity was identified so far. Moreover, no flanking direct repeats were identified. Multiple copies of IS153 were detected by hybridization in other strains of L. sanfranciscensis. Resulting hybridization patterns were shown to differentiate between organisms at strain level rather than a probe targeted against the 16S rDNA. With a PCR based approach IS153 or highly similar sequences were detected in L. acidophilus, L. casei, L. malefermentans, L. plantarum, L. hilgardii, L. collinoides L. farciminis L. sakei and L. salivarius, L. reuteri as well as in Enterococcus faecium, Pediococcus acidilactici and P. pentosaceus.

Amino Acid Sequence↗

Antimicrobial activity in methanolic extracts of several plant species from northern Argentina.

Thirty-nine native plant species were collected from the provinces of Chaco and Formosa, in northern Argentina, and were screened for antimicrobial activity. The plants were dried and extracted thoroughly with methanol. The dry extracts, dissolved in dimethylsulfoxide, were tested for inhibition of microbial growth via microplate assay with an oxidation-reduction dye. The test organisms were: Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus and Enterococcus faecium. Inhibition of respiratory activities in some of these microbial species was produced by the extracts of Astronium balansae, Geoffroea decorticans, Peltophorum dubium, Geoffroea spinosa, Lantana balansae, Prosopis kuntzei, Prosopis ruscifolia and Bulnesia sarmientoi, with minimal inhibitory concentrations (MIC) ranging from 0.08 to 0.5 mg dry matter/ml. Further in vitro experiments measuring the growth of S. aureus in liquid culture confirmed that all of the above extracts at 2 x MIC were able to inhibit bacterial growth effectively, and that some of them (A. balansae, G. decorticans, P. dubium, G. spinosa, P. kuntzei and B. sarmientoi) were able to reduce the initial number of viable counts by at least one order of magnitude in 10 hours, indicating that these extracts should be investigated further for the possible presence of bactericidal components.

Anti-Infective Agents↗

The effects of using lactic acid bacteria inoculants in maize silage on the formation of biogenic amines.

Silages from five ripened varieties of silage maize with dry matter contents ranging between 275 and 410 g/kg were prepared in five laboratory experiments. Whole-plant maize was fermented at 22 degrees C and silages were then stored at the same temperature for 4 months. Spontaneously fermented silages were prepared as control variants and compared with silages inoculated with commercial strains of Lactobacillus plantarum, Lactobzcillus buchneri and a mixed preparation Microsil containing L. plantarum, Lactobacillus casei, Enterococcus faecium and Pediococcus pentosaceus. The starter cultures were applied at doses 5 x 10(5) and 5 x 10(6) CFU/g of chopped maize. Seven biogenic amines and polyamines were extracted from silages with perchloric acid and determined as N-benzamides by micellar electrokinetic capillary chromatography. Common chemical criteria of silage quality were also determined. All three inoculants, mainly at the higher dose, decreased significantly contents of tyramine, putrescine and cadaverine, three undesirable amines occurring at the highest levels. L. plantarum was the most effective. Contents of histamine and tryptamine were low in all experimental silages. Also relatively low were levels of polyamines spermidine and mainly of spermine.

Animals↗

Influence of radiotherapy on intestinal microflora in cancer patients.

We investigated in 15 patients with carcinoma of the uterine cervix or endometrium, who were undergoing postoperative radiation therapy, the effects of different fractionated radiation exposures on counts of fecal bacteria, on the growth of Clostridium difficile and Clostridium perfringens enterotoxin production. We observed a generally significant decrease in intestinal microflora after the first radiation exposure, whereas at the end of radiotherapy all bacteria increased and reached basal values except Enterococcus faecium 1, lactobacilli and total anaerobes. In some patients we observed an overgrowth of some Clostridium spp. which were potential pathogens associated with clinical symptoms. We did not observe an influence of multiple radiations on C. perfringens enterotoxin fecal contents. We conclude that patients receiving radiotherapy may benefit from the intake of oral bacteriotherapy, i.e. live beneficial bacteria such as Bacillus subtilis at the beginning of the irradiation exposure.

Aged↗

Isolation of three new naturally occurring compounds from the culture of Micromonospora sp. P1068.

Bioassay guided isolation of an antibacterial extract prepared from the fermentation broth of a Micromonospora sp. P1068 led to the isolation of eight compounds identified as (3R) 3,4',7-trihydroxy-isoflavanone (1), 3-hydroxydehydrodaidzein, daidzein (2), 3-methyl-1H-indole-2-carboxylic acid (3), 1H-indole-3-carboxaldehyde (4), 3-(p-hydroxyphenyl)-N-methylpropionamide, N-methylphloretamide (5), phenyl acetic acid (6), 2-hydroxy phenyl acetic acid (7) and 4-hydroxy-5-methoxy-benzoic acid (8). Compounds 1 and 5 were found to be novel chemical entities while 3 was isolated from a natural source for the first time. All compounds were evaluated for their antimicrobial activities against a panel of clinically significant microorganisms. Compound 4 was active against Staphylococcus aureus (MIC, 32 microg/ml), Enterococcus faecium (MIC, 32 microg/ml) and Escherichia coli (MIC, 64 microg/ml).

Biological Assay↗

Antimicrobial susceptibility and frequency of occurrence of clinical blood isolates in Europe from the SENTRY antimicrobial surveillance program, 1997 and 1998.

As part of the European arm of the SENTRY Antimicrobial Surveillance Program, 25 European university hospitals referred 9613 blood isolates for in vitro testing against >20 antimicrobial agents. Escherichia coli, Staphylococcus aureus, coagulase-negative Staphylococcus, Pseudomonas aeruginosa, and Klebsiella pneumoniae were the 5 most frequent isolates and accounted for two-thirds of all referrals, with minor regional variation. Of these, approximately 0.36% of E. coli and 16.7% of K. pneumoniae isolates proved to be potential extended-spectrum beta-lactamase producers, and their incidence clearly varied regionally. Quinolone resistance was detected among gram-negative species; in particular, P. aeruginosa and Acinetobacter species. Considerable regional variation was observed in the incidences of methicillin resistance in S. aureus and penicillin resistance in Streptococcus pneumoniae. The incidence of vancomycin resistance in enterococci was relatively low overall and primarily associated with Enterococcus faecium. However, extrapolation of these data to smaller and nonteaching hospitals should be undertaken with caution, since resistance rates may be lower in these facilities.

Anti-Bacterial Agents↗

Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study.

BACKGROUND: Nosocomial bloodstream infections (BSIs) are important causes of morbidity and mortality in the United States. METHODS: Data from a nationwide, concurrent surveillance study (Surveillance and Control of Pathogens of Epidemiological Importance [SCOPE]) were used to examine the secular trends in the epidemiology and microbiology of nosocomial BSIs. RESULTS: Our study detected 24,179 cases of nosocomial BSI in 49 US hospitals over a 7-year period from March 1995 through September 2002 (60 cases per 10,000 hospital admissions). Eighty-seven percent of BSIs were monomicrobial. Gram-positive organisms caused 65% of these BSIs, gram-negative organisms caused 25%, and fungi caused 9.5%. The crude mortality rate was 27%. The most-common organisms causing BSIs were coagulase-negative staphylococci (CoNS) (31% of isolates), Staphylococcus aureus (20%), enterococci (9%), and Candida species (9%). The mean interval between admission and infection was 13 days for infection with Escherichia coli, 16 days for S. aureus, 22 days for Candida species and Klebsiella species, 23 days for enterococci, and 26 days for Acinetobacter species. CoNS, Pseudomonas species, Enterobacter species, Serratia species, and Acinetobacter species were more likely to cause infections in patients in intensive care units (P<.001). In neutropenic patients, infections with Candida species, enterococci, and viridans group streptococci were significantly more common. The proportion of S. aureus isolates with methicillin resistance increased from 22% in 1995 to 57% in 2001 (P<.001, trend analysis). Vancomycin resistance was seen in 2% of Enterococcus faecalis isolates and in 60% of Enterococcus faecium isolates. CONCLUSION: In this study, one of the largest multicenter studies performed to date, we found that the proportion of nosocomial BSIs due to antibiotic-resistant organisms is increasing in US hospitals.

Adolescent↗

Left ventricular assist device-related infection: treatment and outcome.

BACKGROUND: Left ventricular assist device (LVAD) implantation has become an effective treatment option for patients with severe heart failure awaiting transplantation. Significant infection rates have been reported among LVAD recipients. However, few reports have focused specifically on device infection, its treatment, and the impact of LVAD-related infection on clinical outcome. METHODS: Forty-six LVAD-related infections were diagnosed in 38 (50%) of 76 patients who underwent LVAD implantation as a bridge to transplantation. Twenty-nine episodes of LVAD-related bloodstream infection (BSI) (including 5 that were cases of LVAD endocarditis) and 17 episodes of local LVAD infection were identified. RESULTS: Diabetes mellitus appeared to increase the risk of BSI among patients with LVAD infection. LVAD-related infection delayed transplantation, as reflected by longer device-support times (a mean duration +/- SEM of 182.8+/-31.1 days, compared with 66.3+/-8.8 days; P<or=.001). Continuous antimicrobial treatment before, during, and after transplantation was associated with fewer relapses than was a limited course of antibiotics (P<.001). A trend for longer hospital stays after receipt of a transplant and increased early mortality was observed in the cohort with LVAD-related infection, although long-term survival was similar to that associated with patients without LVAD-related infection. Posttransplantation invasive vancomycin-resistant Enterococcus faecium (VREF) infection was diagnosed in 6 patients with LVAD-related infection; 4 of these patients died. No VREF infections were identified in patients without LVAD-related infection. CONCLUSIONS: Our observations suggest that LVAD-related infection is common and may require antimicrobial therapy before, during, and after transplantation, but that it does not prevent successful transplantation. However, patients with LVAD-related infection appear to be at increased risk for invasive VREF infection, which may contribute to early mortality after transplantation.

Anti-Bacterial Agents↗

Trends in antimicrobial resistance in health care-associated pathogens and effect on treatment.

Antimicrobial resistance in health care-associated pathogens is a growing concern for health care and for public health. A recent shift in the epidemiological profile of methicillin-resistant Staphylococcus aureus has resulted not only in health care-associated infections but now, also, in community-associated infections. Reports have described S. aureus exhibiting decreased susceptibility and, even, resistance to vancomycin. The rate of vancomycin resistance among enterococci may be leveling; however, vancomycin resistance in Enterococcus faecium has already achieved high levels. Multidrug resistance in Pseudomonas aeruginosa is increasing, and carbapenem-resistant Klebsiella strains are emerging. Acinetobacter species cause a minority of health care-associated pneumonias due to gram-negative organisms, but a growing proportion is resistant to carbapenems and third-generation cephalosporins. Recent increases in the frequency and severity of Clostridium difficile-associated illness are associated with the emergence of a hypervirulent C. difficile strain with increased resistance to the fluoroquinolones. The presence of these and other resistant organisms in health care facilities limits the number of effective antimicrobials available for treatment.

Anti-Bacterial Agents↗