Active Antimicrobial Agents Research Articles

An update on Legionella

Legionella pneumophila is increasingly recognized as a significant cause of sporadic and epidemic community-acquired and nosocomial-acquired pneumonia. This review focuses on the latest literature concerning the epidemiology, pathogenesis, clinical presentation, diagnosis, and treatment of Legionnaires' disease. A significant increase in the incidence of Legionnaires' disease in the United States has been documented over the last years. L. pneumophila has recently been found to be a leading cause of community-acquired pneumonia in hospitalized and ambulatory patients in Germany. Recent studies provide insight into the understanding of the pathogenesis of Legionnaires' disease and the relevance of the formation of biofilms. Clinical manifestations of Legionnaires' disease are not specific and current diagnostic scores are of limited use. Several recent studies offer useful information concerning Legionnaires' disease in immunosuppressed patients. A systematic review of English literature performed to assess test characteristics of Legionella urinary antigen has found that the pooled sensitivity of the test was 0.74 and specificity was 0.991. Improved clinical response has been observed for patients with Legionnaires' disease treated with highly active antimicrobial agents against Legionella. Legionnaires' disease is a significant health problem in many countries. Clinical manifestations are unreliable in diagnosing Legionnaires' disease. Therefore, diagnostic laboratory tests for Legionella, including the urinary antigen test, should be applied to all patients with pneumonia. Levofloxacin (or other fluoroquinolone) or azithromycin are the current drugs of choice for treatment of Legionnaires' disease. Effective preventive strategies are needed.

Designing of a wheat gluten/montmorillonite based system as carvacrol carrier: Rheological and structural properties

An antimicrobial delivery system was designed from film-forming solutions containing wheat gluten 20% (wt/vol) (WG) as matrix, montmorillonites (Mmt) as structuring agent and carvacrol as active agent (15% wt/wt dry WG). The objectives of this work were to understand how the addition of montmorillonites (0–10% wt/wt dry WG) affects the carvacrol retention capacity of both the film forming solution and the resulting film obtained by casting. For this purpose, structural, granulometric and rheological changes that occurred in the film-forming solutions were studied. The introduction of carvacrol in a WG solution containing increasing amounts of Mmt resulted in dramatic changes in its rheological behaviour. Depending on the Mmt amount added (<or ≥ 5%), the viscosity evolved in different ways indicating an unexpected and specific effect of Mmt on the WG solutions that contain carvacrol. In the presence of a sufficiently high Mmt content (≥5%), particles size measurements and microscopic observations pointed out large aggregated structures. These aggregated structures were supposed to result in an entrapment of carvacrol molecules that could be responsible for a higher carvacrol retention exhibited by both WG film-forming solutions and cast films. Further indications of this assumption were provided by XRD measurements that confirmed the establishment of specific interactions between Mmt, carvacrol and WG. The investigated delivery system based on a WG matrix reinforced by high content of Mmt fillers (≥5%) was clearly efficient to retain and protect an antimicrobial active agent such as carvacrol during the processing stage.

Risk factors and impact of nosocomial Acinetobacter baumannii bloodstream infections in the adult intensive care unit: a case–control study

During a nine-year study period, 96 episodes of nosocomial bloodstream infection (BSI) due to Acinetobacter baumannii were identified in the adult intensive care units (ICUs) of Shin Kong Wu Ho-Su Memorial Hospital. Seventy-seven (80.2%) of these were available for matching in terms of age, sex, primary diagnosis of ICU admission, ICU ward, and disease severity. Univariate analysis showed that central venous catheter use, ventilator use, prior A. baumannii colonisation, and respiratory and cardiovascular organ failure were significantly associated with acquiring A. baumannii BSI in the ICU. By multivariate analysis, only prior A. baumannii colonisation [odds ratio (OR): 3.81; P<0.001] and cardiovascular failure (OR: 2.24; P=0.04) were identified as independent risk factors. The lower respiratory tract (32/77; 41.6%) was the most frequent source of infection, followed by intravascular catheters (13/77; 16.9%). Cumulative survival curves for patients with A. baumannii BSI and control patients showed no significant difference (30 day crude mortality: 29.9% and 27.3%, respectively; P=0.916). However, the mean length of ICU and hospital stay and mean hospital cost of patients with A. baumannii BSI significantly increased, with an estimated 8.7 days excess length of ICU stay, 19.1 days excess hospital stay, and US $8480 extra hospital costs. Imipenem and meropenem remained the most active antimicrobial agents, both with 95.5% susceptibility (MIC50=0.25 and 0.5, respectively). Improving hand hygiene of healthcare workers and aseptic care of vascular catheters and endotracheal tubes are important measures to prevent A. baumannii colonisation and decrease the incidence of BSI.

Nosocomial Burkholderia cepacia infections in a Turkish university hospital: a five-year surveillance

Burkholderia cepacia has the potential to cause fatal infections in ICUs, and multidrug resistance makes them a serious threat in hospital settings. The aim of this study was to evaluate the epidemiology of B. cepacia infections in our hospital. The incidence, clinical characteristics, antimicrobial susceptibility, and outcomes of nosocomial B. cepacia infections during a five-year period were retrospectively analysed according to the infection control committee records. A total of 39 cases with nosocomial B. cepacia infection were included in the study. B. cepacia was identified from 0.7% of the nosocomial isolates. Its incidence was 0.26 per 1,000 admissions with 53.8% crude mortality rate. The most frequent nosocomial B. cepacia infection was pneumonia (58.9%), followed by bloodstream infections (25.6%), surgical site infections (7.6%), urinary tract infections, (5.1%), and skin-soft tissue infections (2.5%). Nosocomial B. cepacia infections were most commonly observed in intensive care units (61.5%). The most active antimicrobial agents were piperacillin-tazobactam, cefoperazone-sulbactam, and carbapenems. The incidence of nosocomial B. cepacia infections was rare in our hospital, and no outbreak was detected during the study period. However, infections caused by B. cepacia should be taken into consideration because of their high mortality due to multidrug resistance in ICU settings.

Antimicrobial susceptibility of tigecycline and comparators against bacterial isolates collected as part of the TEST study in Europe (2004–2007)

Tigecycline is a broad-spectrum antimicrobial agent that has been approved for the treatment of skin and soft-tissue infections as well as intra-abdominal infections. The Tigecycline Evaluation and Surveillance Trial (TEST) is a global, longitudinal surveillance study established in 2004 to monitor the in vitro activity of tigecycline and comparator agents against key Gram-negative and Gram-positive pathogens. This report examines data obtained for 24 748 isolates collected across 24 European countries between 2004 and 2007. Tigecycline, meropenem and imipenem were the most active antimicrobial agents against most Gram-negative isolates including multidrug-resistant Acinetobacter baumannii (15.7% of the A. baumannii isolates in this study), extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (8.5% of E. coli) and ESBL-producing Klebsiella pneumoniae (13.6% of K. pneumoniae). Only amikacin was active against >90% of Pseudomonas aeruginosa isolates (92.8% susceptible). Tigecycline, linezolid and vancomycin were the most active agents against Gram-positive agents across Europe between 2004 and 2007, with tigecycline displaying the lowest MIC 90 values (minimum inhibitory concentration for 90% of the organisms) against meticillin-resistant Staphylococcus aureus (26.5% of the collected S. aureus isolates), vancomycin-resistant Enterococcus faecium (15.7% of the E. faecium strains) and penicillin-resistant Streptococcus pneumoniae (9.3% of the S. pneumoniae strains). Longitudinal analysis showed no increase in tigecycline MIC values over the 4-year study period, whilst increased resistance was noted for several comparator agents.

Synthesis, Structural, and Antibacterial Studies of Some Transition Metal Complexes Derived from Thiosemicarbazone and Semicarbazone

A series of metal complexes of Pd(II), Pt(II), Rh(III), Ir(III), and Ru(III) with thiosemicarbazone and semicarbazone of 2-acetyl thiophene have been synthesized. Their structures were determined on the basis of elemental analyses; molar conductance; magnetic susceptibility measurements; and IR, 1 H NMR, and electronic spectral studies. On the basis of molar conductance, the complexes may be formulated as [M(L)2]Cl2 and [M′(L)2Cl2]Cl [where M = Pd(II), Pt(II) and M′ = Rh(III), Ir(III), and Ru(III)] due to their 1:2 and 1:1 electrolytic nature. On the basis of IR, 1H NMR, and electronic spectral studies, an octahedral geometry has been assigned for Rh(III), Ir(III), and Ru(III), while square planar geometry has been assigned for the Pd(II) and Pt(II) complexes. The synthesized ligands and their complexes have been screened for bactericidal activity against several bacterial species (i.e., B. macerans, A. aureus, E. coli), and it is shown that the metal complexes act as more active antimicrobial agents than the uncomplexed ligands from which they derive.

Synthesis of some pyrazolyl benzenesulfonamide derivatives as dual anti-inflammatory antimicrobial agents

Four series of pyrazolylbenzenesulfonamide derivatives were synthesized and evaluated for their anti-inflammatory activity using cotton pellet induced granuloma and carrageenan-induced rat paw edema bioassays. Moreover, COX-1 and COX-2 inhibitory activity, ulcerogenic effect and acute toxiCIT000y were also determined. Furthermore, the target compounds were screened for their in-vitro antimicrobial activity against Eischerichia coli, Staphylococcus aureus and Candida albicans. Compounds 4-(3-Phenyl-4-cyano-1H-pyrazol-1-yl)benzenesulfonamide 9a and 4-(3-Tolyl-4-cyano-1H-pyrazol-1-yl)benzenesulfonamide 9b were not only found to be the most active dual anti-inflammatory antimicrobial agents in the present study with good safety margin and minimal ulcerogenic effect but also exhibited good selective inhibitory activity towards COX-2. A docking pose for 9a and 9b separately in the active site of the human COX-2 enzyme was also obtained. Therefore, these compounds would represent a fruitful matrix for the development of dual anti-inflammatory antimicrobial candidates with remarkable COX-2 selectivity.

Regioselective synthetic approaches towards 1,2,8,9-tetraazadispiro[4.1.4.2]trideca-2,9-dien-6-ones of potential antimicrobial properties

Reaction of 2,5-bis(arylmethylidene)cyclopentanones 1a– d with nitrilimines (generated in situ via triethylamine dehydrohalogenation of the corresponding hydrazonoyl chlorides 2a, b) in 1:2 molar ratio proceeds in a high regioselective manner affording monocycloadducts 3 and dicycloadducts in the form of two isomers 4, 5. Single crystal X-ray diffraction studies of the isolated crystalline form of 3c support the established structure and indicate that the formed product is 7 E, 4 S, 5 R. Antimicrobial activity screening of the synthesized compounds 3– 5, utilizing a variety of Gram-positive ( Staphylococcus aureus, Enterococcus fecalis and Streptococcus agalactiae), Gram-negative bacteria ( Escherichia coli, Klebsiella pneumoniae and Proteus vulgaris) and yeast ( Candida albicans), exhibited that all the prepared analogues acquire promising activities against both Gram-positive and Gram-negative bacteria especially compounds 3b, 4a (antimicrobial active agents against Gram-positive bacteria) and 3c (antimicrobial active agent against Gram-negative bacteria).

Antimicrobial Resistance Rates of Enterobacter spp.: A Seven-Year Surveillance Study

Objective: The aim of the study was to evaluate the trends of antimicrobial resistance of Enterobacter spp. over time in a Saudi Arabian hospital. Materials and Methods: This is an in vitro surveillance study of the antibiotic susceptibility pattern among Enterobacter spp. recovered from outpatient and nosocomial isolates over a 7-year period from 2000 to 2006. Only a single isolate per patient was included. Results: A total of 1,394 nonrepetitive isolates were analyzed during the study period. Enterobactercloacae and Enterobacteraerogenes constituted 60 and 33% of the isolates, respectively. Overall, there was no statistically significant increase in the resistance rates over time for the outpatient and nosocomial isolates of Enterobacter. For E.cloacae, nosocomial isolates were statistically more resistant than outpatient isolates to ceftriaxone (17.5 vs. 5.5%), ciprofloxacin (9.5 vs. 4.7%), ticarcillin (42.8 vs. 25.4%) and ticarcillin-clavulanic acid (23 vs. 9.3%). For E.aerogenes, the nosocomial isolates were also more resistant to ceftriaxone and ciprofloxacin than the outpatient isolates (9.2 vs. 2.4% and 9.6 vs. 3%, respectively). In addition, nosocomial isolates of E.aerogenes were more resistant to piperacillin (25 vs. 15.6%) and ticarcillin-clavulanic acid (32 vs. 10.2%) than outpatient isolates. The most active antimicrobial agents were imipenem, amikacin and gentamicin against Enterobacter. Resistance rate to ≥3 classes of antibiotics was present in 2.5% of nosocomial and 1.7% of outpatient isolates (p = 0.78). Conclusion: The resistance rate for the outpatient and nosocomial isolates of Enterobacter had remained relatively stable over the study period. The most active antimicrobial agents were imipenem, amikacin and gentamicin.

Spectroscopic and biological approach in the characterization of Cr(III), Mn(II) and Co(II) complexes with a novel hexaazamacrocyclic ligand derived from semicarbazide

Complexes of Cr(III), Mn(II) and Co(II) with a novel 5,7,12,14-tetraphenyl- 1,2,4,8,10,11-hexaazacyclotetradecane-3,9-dione macrocyclic ligand, THTD (L), were synthesized and characterized by elemental analysis, molar conductance and magnetic susceptibility measurements, as well as by mass, 1H-NMR, IR, electronic and EPR spectral studies. Based on the spectral studies, an octahedral geometry was assigned for the Cr(III), Mn(II) and Co(II) complexes. The ligand and its complexes were screened in vitro against some species of bacteria and plant pathogenic fungi. The metal complexes were found to be more active antimicrobial agents than the free ligand from which they were derived.

The Problem of Antimicrobial Resistance in Nosocomial Medical and Surgical Intensive Care Units Infections in a University Hospital; a Two-Year Prospective Study

Aim: To determine the frequency of nosocomial infections (NIs) and the antimicrobial resistance of pathogens isolated from patients admitted to 4 intensive care units (ICUs) at a university hospital. Materials and Methods: The patients were prospectively followed over 2 years in medical, surgical, and reanimation ICUs. The isolates were collected from patients with NI determined by the Center for Diseases Control and Prevention criteria. The identification was performed and susceptibility to antibiotics was determined in an automated system Sceptor (Becton Dickinson) as described by the CCLS. Results: Among the 3962 patients in the ICUs, total NI incidence was 6.9%, with the highest rate in the reanimation ICU (14.7%) and the lowest rate in the surgical ICU (2.5%). In all, 492 NI episodes were diagnosed in 272 patients. The incidence of NIs was 13.1 per 1000 patient days. The NIs were urinary tract infections (32%), primary blood stream infections (24%), pneumonia (20%), surgical-site infections (13%), and other infections (11%). Pneumonia was the most common NI in the reanimation ICU (54%). The pathogens were 39% gram-positive bacteria, 52% gram-negative bacteria, and 9% Candida species. S. aureus (18%) was the most frequently isolated bacteria, followed by P. aeruginosa (16%), Acinetobacter spp. (10%), coagulase negative staphylococcus (CNS) (10%), Klebsiella (9%), E. coli (9%), and Enterococcus spp. (9%). Resistance to methicillin was 90% in S. aureus isolates and was 95% in the CNS isolates; no resistance was detected to vancomycin in S. aureus and CNS isolates. Eight percent of Enterococcus isolates were resistant to vancomycin. Against the gram-negative bacteria the carbapenems were most active, followed by amikacin and ciprofloxacin. Five percent of P. aeruginosa and 15% of Acinetobacter spp. were resistant to all antibiotics. The most active antimicrobial agents against Acinetobacter spp. were imipenem (73%) and tobramycin (46%); against Pseudomonas spp. were ticarcillin/clavulanate (56%), piperacillin (44%), and imipenem (33%); against Klebsiella spp. was imipenem (92%); against E. coli were imipenem (94%), amikacin (94%), and ciprofloxacin (74%); and against Enterobacter spp. were ciprofloxacin (89%) and imipenem (78%). Conclusions: The high rates of resistant pathogens responsible for NI in ICUs suggest that infection preventive procedures should be implemented and antimicrobial agents must be used appropriately.

Emergence and widespread dissemination of OXA-23, -24/40 and -58 carbapenemases among Acinetobacter spp. in Asia-Pacific nations: report from the SENTRY Surveillance Program

The aim of this study was to evaluate the occurrence and dissemination of acquired carbapenem-hydrolysing class D beta-lactamase (class D carbapenemase)- and metallo-beta-lactamase (MBL)-encoding genes among Acinetobacter spp. isolates recovered from medical centres in the Asia-Pacific (APAC) region. During 2006-07, 41 medical centres located in 10 countries in the APAC region forwarded to a central monitoring site 544 Acinetobacter spp. isolates, which were tested for susceptibility by the reference broth microdilution method. Isolates non-susceptible to imipenem or meropenem (MIC>or=8 mg/L) were screened for OXA-23-, OXA-24/40-, OXA-58- and MBL-encoding genes and confirmed by sequencing. Clonality was assessed by ribotyping and PFGE. Polymyxins (99.1% susceptible) and tigecycline (98.9% susceptible) were the most active antimicrobial agents tested. Among the isolates, 230 (42.3%) were non-susceptible to imipenem or meropenem, and class D carbapenemase- or MBL-encoding genes were detected in 162 (70.4%). blaOXA-23 was found in isolates recovered from six countries, while blaOXA-24/40 and blaOXA-58 were less common. Several isolates harboured more than one class D carbapenemase, and MBL-encoding genes were detected in one Acinetobacter johnsonii from the Philippines (blaIMP-4) and one Acinetobacter baumannii from Korea (blaVIM-2)). Overall, clonal dissemination was noted within medical centres; however, genetic relatedness was also noted among class D carbapenemase-producing A. baumannii isolates recovered from different countries. This study shows a high distribution of class D carbapenemase-encoding genes, mainly blaOXA-23, in Acinetobacter spp. isolates. In addition, clonal dissemination among medical centres located in different countries in the APAC region, previously documented in many regions of Europe, emphasizes the epidemic potential of these bacteria.

An insight into the salivary transcriptome and proteome of the soft tick and vector of epizootic bovine abortion, Ornithodoros coriaceus.

The salivary glands of blood-sucking arthropods contain a redundant 'magic potion' that counteracts their vertebrate host's hemostasis, inflammation, and immunity. We here describe the salivary transcriptome and proteomics (sialome) of the soft tick Ornithodoros coriaceus. The resulting analysis helps to consolidate the classification of common proteins found in both soft and hard ticks, such as the lipocalins, Kunitz, cystatin, basic tail, hebraein, defensin, TIL domain, metalloprotease, 5'-nucleotidase/apyrase, and phospholipase families, and also to identify protein families uniquely found in the Argasidae, such as the adrenomedullin/CGRP peptides, 7DB, 7 kDa, and the RGD-containing single-Kunitz proteins. Additionally, we found a protein belonging to the cytotoxin protein family that has so far only been identified in hard ticks. Three other unique families common only to the Ornithodoros genus were discovered. Edman degradation, 2D and 1D-PAGE of salivary gland homogenates followed by tryptic digestion and HPLC MS/MS of results confirms the presence of several proteins. These results indicate that each genus of hematophagous arthropods studied to date evolved unique protein families that assist blood feeding, thus characterizing potentially new pharmacologically active components or antimicrobial agents.

Delay of Active Antimicrobial Therapy and Mortality among Patients with Bacteremia: Impact of Severe Neutropenia

Increasing bacterial antimicrobial resistance has prompted physicians to choose broad-spectrum antimicrobials in order to reduce the likelihood of inactive empirical therapy. However, for bacteremic patients already receiving supportive care, it is unclear whether delay of active antimicrobial therapy significantly impacts patient outcomes. We performed a retrospective cohort study of patients with monomicrobial bloodstream infections at a large urban hospital in the United States from 2001 to 2006. We assessed the impact of delay of active antimicrobial therapy on mortality by using multivariable logistic regression modeling with and without propensity score methodology. We evaluated 1,523 episodes of monomicrobial bacterial bloodstream infections at our institution. Nine hundred eighty-three bacteremic episodes (64.5%) were treated with an active antimicrobial agent within 24 h of the index blood culture; the remaining 540 episodes (35.5%) were considered to have delay of active antimicrobial therapy. In adjusted analysis, among patients in the non-intensive-care-unit setting with an absolute neutrophil count (ANC) of <100 cells/microl, delay was associated with increased mortality (odds ratio [OR], 18.0; 95% confidence interval [CI], 2.84 to 114.5; P < 0.01); among intensive-care-unit patients with an ANC of <100 cells/microl, the effect of delay on mortality was nearly significant (OR, 5.56; 95% CI, 0.85 to 36.3; P = 0.07). However, for patients who were nonneutropenic (ANC, >500 cells/microl) or had ANCs of 100 to 500 cells/microl, delay was not associated with increased mortality. While the delay of active antimicrobial therapy was not significantly associated with higher mortality for most patients in this cohort, patients with severe neutropenia appeared to be vulnerable.

In vitro susceptibility of genotypically distinct and clonal Clostridium difficile strains to oritavancin

Clostridium difficile infection is a nosocomial disease of increasing importance. First-line treatment is limited to metronidazole or vancomycin. Oritavancin is a lipoglycopeptide with activity against Gram-positive bacteria, including drug-resistant pathogens. MICs of oritavancin, metronidazole and vancomycin for genotypically distinct C. difficile strains, including epidemic C. difficile PCR ribotypes 001 and 027, were determined by agar incorporation and broth macrodilution methods. In agar incorporation methods, the impact of supplements on oritavancin MICs was tested to address oritavancin binding to surfaces. Thirty-three genotypically distinct C. difficile strains were identified by PCR ribotyping. Wilkins Chalgren agar incorporation plates containing oritavancin, metronidazole and vancomycin were prepared with and without 0.002% polysorbate-80 (P80) and lysed horse blood (2%). Broth macrodilution MICs of oritavancin, metronidazole and vancomycin were determined in Brucella broth. Inoculated agar incorporation plates and broth macrodilution tubes were cultured anaerobically at 37 degrees C for 48 h. Broth macrodilution MICs were lower than agar incorporation MICs for oritavancin, but not for metronidazole and vancomycin. Oritavancin broth macrodilution MIC(90)s were 2- to 4-fold lower than the corresponding agar incorporation MIC(90)s, while geometric mean MICs were >5-fold lower. Oritavancin broth macrodilution MIC(90)s were approximately 2- and 5-fold lower than those for metronidazole and vancomycin. Metronidazole was the most active antimicrobial agent against C. difficile using agar incorporation methods. Oritavancin agar incorporation MIC(90)s were unaffected by 0.002% P80 and/or 2% lysed horse blood. Oritavancin was at least 4-fold more potent than vancomycin against the majority (25/33) of C. difficile strains tested by broth macrodilution. Oritavancin activity may be underestimated by agar incorporation methods, regardless of the use of P80 or lysed horse blood.

Antimicrobial activity of various parts of Polyalthia longifolia var. pendula: isolation of active principles from the leaves and the berries

Methanol extracts of leaves, stem, twigs, green berries, flowers, roots, root-wood and root-bark of Polyalthia longifolia var. pendula, were tested for their antibacterial and antifungal potentials. Bioassay monitored isolation work on the methanol extract of leaves and berries which possess promising antibacterial activity led to the isolation of seven clerodane diterpenoids, 16(R and S)-hydroxy-cleroda-3,13(14)Z-dien-15,16-olide (1), 16-oxo-cleroda-3,13(14)E-dien-15-oic acid (2), methyl-16-oxo-cleroda-3,13(14)E-dien-15-oate (3), 2-oxo-kolavenic acid (4), 16 (R and S)-hydroxy-cleroda-3,13(14)Z-dien-15,16-olide-2-one (5), (4-->2)-abeo-16(R and S)-hydroxy-cleroda-2,13(14)Z-dien-15,16-olide-3-al (6), 3beta,16alpha-dihydroxy-cleroda-4(18), 13(14)Z-dien-15,16-olide (7), while kolavenic acid (8) and solidagonal acid (9) were obtained from the root-wood. Diterpenoids 1 and 8 were also obtained from the root-bark. It is the first report of the isolation of 7 and 9 from this source, and clerodane 3 was obtained as a natural product for the first time. Clerodanes 1, 2, 5, 6 and 7 were found to be active antimicrobial agents with MIC values ranging between 7.8 and 500 microg/mL. Diterpenoid 1 emerged as the most active antimicrobial agent. The acetyl derivative (10) of 1 and the methyl derivative (3) of 2 were found to be less active than the parent compounds. A complex of allantoin was also obtained from the berries, which on hydrolysis furnished pure allantoin (11).

In vitro activity of ertapenem and other carbapenems against extended-spectrum beta-lactamase producing Escherichia coli and Klebsiella pneumoniae clinical isolates in a tertiary care center in Turkey

Objective: To evaluate the in vitro effect of ertapenem, imipenem and meropenem in clinical isolates of extended-spectrum β-lactamase (ESBL)-producing strains of Escherichia coli and Klebsiella pneumoniae. Design/methods: We studied 82 consecutive clinical isolates of ESBL-producing E. coli (n = 49) and K. pneumonia (n = 33) between February 2006 and September 2007. The minimum inhibitory concentration for each carbapenem was determined using the agar dilution method. Results: Eighty two consecutive microorganisms from sterile sites were evaluated. A total of 48.8% of patients had a history of surgical intervention, 78.0% needed urinary catheterization, 57.3% required vascular access and 40.3% mechanical ventilation; and 70.7% had a history of ICU stay. High resistance rates were shown for both E. coli and K. pneumoniae against cefepime (81.7%), ciprofloxacin (50.9%), tetracycline (75.0%), co-trimoxazole (47.4%), and gentamicin (48.7%). In addition, most K. pneumoniae and E. coli isolates were susceptible to amikacin (78.3%) and piperacilline-tazobactam (91.5%). Meropenem and imipenem showed activity against 100% of the isolates. Ertapenem showed activity against 100% of K. pneumoniae isolates, against 95.9% of E. coli isolates and against 97.5% of the 82 ESBL-producing microorganisms. Two E. coli isolates showed ertapenem resistance. Conclusion: In recent literature, carbapenems were the most active antimicrobial agents against ESBL-producing Enterobacteriaceae, as in our study. This is the first study on the in vitro activity of ertapenem against ESBL-producing E. coli and K. pneumoniae conducted in Turkey. In view of the serious infections caused by ESBL-producing microorganisms, therapeutic interventions are still problematic in serious clinical conditions. Ertapenem may be a good choice for treatment, with the additional advantage of being a once a day regimen.

Use of Corticosteroids in Treating Infectious Diseases

Clinicians have generally avoided prescribing corticosteroids for active infection because of their known immunosuppressive effects and concern about long-term complications. We conducted a review of the published randomized, double-blind trials comparing corticosteroids and placebo in infections. Except in some trials of viral infections, sore throat, and cerebral cysticercosis, all patients also received active antimicrobial agents in addition to placebo or corticosteroids. For patients with bacterial meningitis, tuberculous meningitis, tuberculous pericarditis, severe typhoid fever, tetanus, or pneumocystis pneumonia with moderate to severe hypoxemia, treatment with corticosteroids improved patient survival (group 1 infections). For patients with bacterial arthritis, corticosteroids were also beneficial and reduced long-term disability (group 2 infections). For about a dozen other infections, corticosteroids significantly relieved symptoms (group 3 infections), and clinicians should consider using them if symptoms are substantial. Corticosteroids were harmful in 2 infections, viral hepatitis and cerebral malaria (group 5 infections). We conclude that corticosteroids are beneficial and safe for a wide variety of infections, although courses longer than 3 weeks should be withheld from patients with concomitant human immunodeficiency virus infection and low CD4 counts.

Synthesis of silver nanoparticles using hydroxyl functionalized ionic liquids and their antimicrobial activity.

We report a new one phase method for the synthesis of uniform monodisperse crystalline Ag nanoparticles in aqueous systems that has been developed by using newly synthesized mono and dihydroxylated ionic liquids and cationic surfactants based on 1,3-disubstituted imidazolium cations and halogens anions. The hydroxyl functionalized ionic liquids (HFILs) and hydroxyl functionalized cationic surfactants (HFCSs) also simultaneously acts both as the reductant and protective agent. By changing the carbon chain length, alcohol structure and anion of the 1,3-imidazolium based HFILs and HFCSs the particle size, uniform and dispersibility of nanoparticles in aqueous solvents could be controlled. Transmission electron microscopy (TEM), electron diffraction, UV-Vis and NMR, were used for characterization of HFILs, HFCSs and silver nanoparticles. TEM studies on the solution showed representative spherical silver nanoparticles with average sizes 2–8 nm, particularly 2.2 nm and 4.5 nm in size range and reasonable narrow particle size distributions (SD-standard distribution) 0.2 nm and 0.5 nm respectively. The all metal nanoparticles are single crystals with face centered cubic (fcc) structure. The silver nanoparticles surface of plasmon resonance band (λmax) around 420 nm broadened and little moved to the long wavelength region that indicating the formation of silver nanoparticles dispersion with broad absorption around infrared (IR) region. Silver complexes of these HFILs as well as different silver nanoparticles dispersions have been tested in vitro against several gram positive and gram negative bacteria and fungus. The silver nanoparticles providing environmentally friendly and high antimicrobial activity agents.

Antibacterial Activity And Phytochemical Screening Of Crude Ethanolic Extract Of Leaves Of Ocimum Gratissimum L On Listeria Monocytogenes.

Ethanolic extract of the leaves of Ocimum gratissimum was screened for its phytochemical and antibacterial properties on Listeria monocytogenes at varying concentrations. The Agar gel diffusion method was used to assay for the antibacterial properties on the test isolate. The results showed that the ethanolic extracts at different concentrations inhibited the growth of Listeria monocytogenes. The concentration of 250mg/ml inhibited the isolate with highest diameter zone of inhibition of 25mm. The extracts inhibited the growth of the bacterial isolate in a concentration dependent manner with MICs of 9.25mg/ml, while MBCs had 2.15mg/ml. Phytochemical analysis of the leaf extracts revealed the presence of antimicrobial active agents such as alkaloids, cardiac glycosides, flavonoids, glycosides, resins, steroidal terpens, and tannins. These established a good support to the use of this plant in herbal medcine and as base for the development of new drugs and phytomedicine.