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Stool samples from 38 travelers returning from India were screened for extended-spectrum cephalosporin- and carbapenem-resistant Enterobacteriaceae implementing standard selective plates. Twenty-six (76.3%) people were colonized with CTX-M or DHA producers, but none of the strains was colistin resistant and/or mcr-1 positive. Nevertheless, using overnight enrichment and CHROMagar Orientation plates supplemented with colistin, four people (10.5%) were found to be colonized with colistin-resistant Escherichia coli . One cephalosporin-susceptible sequence type 10 (ST10) strain carried a 4,211-bp IS Apl1-mcr-1 -IS Apl1 element in an IncHI2 plasmid backbone.

Background. Cadmium (Cd), a diffused environmental pollutant, has adverse effects on urinary apparatus. The role of flavocoxid, a natural flavonoid with antioxidant activity, on the morphological and biochemical changes induced in vivo by Cd in mice kidney was evaluated. Methods. C57 BL/6J mice received 0.9% NaCl alone, flavocoxid (20 mg/kg/day i.p.) alone, Cd chloride (CdCl2) (2 mg/kg/day i.p.) alone, or CdCl2 plus flavocoxid (2 mg/kg/day i.p. plus 20 mg/kg/day i.p.) for 14 days. The kidneys were processed for biochemical, structural, ultrastructural, and morphometric evaluation. Results. Cd treatment alone significantly increased urea nitrogen and creatinine, iNOS, MMP-9, and pERK 1/2 expression and protein carbonyl; reduced GSH, GR, and GPx; and induced structural and ultrastructural changes in the glomeruli and in the tubular epithelium. After 14 days of treatment, flavocoxid administration reduced urea nitrogen and creatinine, iNOS, MMP-9, and pERK 1/2 expression and protein carbonyl; increased GSH, GR, and GPx; and showed an evident preservation of the glomerular and tubular structure and ultrastructure. Conclusions. A protective role of flavocoxid against Cd-induced oxidative damages in mouse kidney was demonstrated for the first time. Flavocoxid may have a promising antioxidant role against environmental Cd harmful effects on glomerular and tubular lesions.

WOS: 000389233700014, PubMed ID: 27717604, This article describes the prevalence of antibiotic resistance and predictors of mortality for healthcare-associated (HA) Gram-negative bloodstream infections (GN-BSI). In total, 831 cases of HA GN-BSI from 17 intensive care units in different centres in Turkey were included; the all-cause mortality rate was 44%. Carbapenem resistance in Klebsiella pneumoniae was 38%, and the colistin resistance rate was 6%. Multi-variate analysis showed that age > 70 years [odds ratio (OR) 2, 95% confidence interval (CI) 1.22-3.51], central venous catheter use (OR 2.1, 95% CI 1.09-4.07), ventilator- associated pneumonia (OR 1.9, 95% CI 1.1-3.16), carbapenem resistance (OR 1.8, 95% CI 1.11-2.95) and APACHE II score (OR 1.1, 95% CI 1.07-1.13) were significantly associated with mortality. (C) 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Klebsiella pneumoniae is an important multidrug-resistant (MDR) pathogen affecting humans and a major source for hospital infections associated with high morbidity and mortality due to limited treatment options. We summarize the wide resistome of this pathogen, which encompasses plentiful chromosomal and plasmid-encoded antibiotic resistance genes (ARGs). Under antibiotic selective pressure, K. pneumoniae continuously accumulates ARGs, by de novo mutations, and via acquisition of plasmids and transferable genetic elements, leading to extremely drug resistant (XDR) strains harboring a 'super resistome'. In the last two decades, numerous high-risk (HiR) MDR and XDR K. pneumoniae sequence types have emerged showing superior ability to cause multicontinent outbreaks, and continuous global dissemination. The data highlight the complex evolution of MDR and XDR K. pneumoniae, involving transfer and spread of ARGs, and epidemic plasmids in highly disseminating successful clones. With the worldwide catastrophe of antibiotic resistance and the urgent need to identify the main pathogens that pose a threat on the future of infectious diseases, further studies are warranted to determine the epidemic traits and plasmid acquisition in K. pneumoniae. There is a need for future genomic and translational studies to decipher specific targets in HiR clones to design targeted prevention and treatment.

JUSTIFICATIVA E OBJETIVOS: Com base nos conhecimentos sobre a ação antiinflamatória e antibacteriana dos anestésicos locais (AL) o estudo teve como objetivo determinar o efeito da lavagem peritoneal com solução de bupivacaína na sobrevida de ratos com peritonite fecal por fezes autógenas. MÉTODO: Foram utilizados 48 ratos da linhagem Wistar, com peso entre 300 g e 330 g (311,45 ± 9,67), submetidos à laparotomia seis horas após a indução de peritonite, distribuídos aleatoriamente em quatro grupos: 1 - Controle, nenhum tratamento (n = 12); 2 - Enxugamento da cavidade abdominal (n = 12); 3 - Lavagem da cavidade abdominal com 3 mL de solução fisiológica a 0,9% e enxugamento (n = 12); 4 - Lavagem da cavidade abdominal com 8 mg.kg-1 (± 0,5 mL) de bupivacaína 0,5%, adicionada a 2,5 mL de solução fisiológica a 0,9% e enxugamento (n = 12). Os animais que faleceram foram necropsiados e o horário do óbito foi anotado. Os animais sobreviventes foram mortos no 11° dia do pós-operatório e realizou-se a necropsia. RESULTADOS: Houve 100% de mortalidade nos animais do Grupo 1, em 52 horas, 100% nos animais do Grupo 2, em 126 horas e 50% nos animais do Grupo 3 em 50 horas. Os animais do Grupo 4 sobreviveram. A sobrevida, no 11º dia de pós-operatório, foi maior nos grupos 3 e 4 com relação aos grupos 1 e 2 (p < 0,001) e maior nos Grupo 4 com relação ao Grupo 3 (p < 0,01). CONCLUSÕES: A lavagem peritoneal com solução de bupivacaína diluída em solução fisiológica foi eficaz para evitar o óbito, por 11 dias, em 100% dos animais com peritonite fecal. BACKGROUND AND OBJECTIVES: Based on the knowledge of the anti-inflammatory and anti-bacterial actions of local anesthetics (LA), the objective of this study was to determine the effects of peritoneal lavage with bupivacaine on survival of mice with fecal peritonitis. METHODS: Forty-eight Wistar mice, weighing between 300 and 330 g (311.45 ± 9.67 g), undergoing laparotomy 6 hours after induction of peritonitis were randomly divided in 4 groups: 1 - Control, without treatment (n = 12); 2 - Drying of the abdominal cavity (n = 12); 3 - Lavage with 3 mL NS and posterior drying of the abdominal cavity (n = 12); and 4 - Lavage with 8 mg.kg-1 (± 0.5 mL) of 0.5% bupivacaine added to 2.5 mL of NS followed by drying out of the abdominal cavity (n = 12). Animals that died underwent necropsy and the time of death was recorded. Surviving animals were killed on the 11th postoperative day and underwent necropsy. RESULTS: Group 1 presented a 100% mortality rate in 52 hours, 100% mortality rate in Group 2 in 126 hours, and Group 3 presented a 50% mortality rate in 50 hours. Animals in Group 4 survived. Survival on the 11th day was greater in groups 3 and 4 than in Groups 1 and 2 (p < 0.001) and greater in Group 4 than in Group 3 (p < 0.01). CONCLUSIONS: Peritoneal lavage with a solution of bupivacaine diluted in NS was effective in preventing death for 11 days in 100% of animals with fecal peritonitis. JUSTIFICATIVA Y OBJETIVOS: Basados en los conocimientos sobre la acción antiinflamatoria y antibacteriana de los anestésicos locales (AL), el estudio tuvo el objetivo de verificar el efecto del lavado peritoneal con solución de bupivacaína en la sobrevida de ratones con peritonitis fecal por heces autógenas. MÉTODO: Se usaron 48 ratones de la raza Wistar, con peso entre 300 g y 330 g (311,45 ± 9,67), sometidos a la laparotomía 6 horas después de la inducción de peritonitis, distribuidos aleatoriamente en 4 grupos: 1 - Control, ningún tratamiento (n = 12); 2 - Secado de la cavidad abdominal (n = 12); 3 - Lavado de la cavidad abdominal con 3 mL de solución fisiológica a 0,9% y secado (n = 12); 4 - Lavado de la cavidad abdominal con 8 mg.kg-1 (± 0,5 mL) de bupivacaína 0,5%, adicionada a 2,5 mL de solución fisiológica a 0,9% y secado (n = 12). Los animales que murieron fueron llevados a necropsia y el horario del óbito se anotó. Los animales sobrevivientes se sacrificaron al 11º día del postoperatorio y se realizó la necropsia. RESULTADOS: Hubo un 100% de mortalidad en los animales del Grupo 1 en 52 horas, 100% en los animales del Grupo 2, en 126 horas y un 50% en los animales del Grupo 3 en 50 horas. Los animales del Grupo 4 sobrevivieron. La sobrevida, al 11° día del postoperatorio, fue mayor en los grupos 3 y 4 con relación a los grupos 1 y 2 (p < 0,001) y mayor en los Grupo 4 con relación al Grupo 3 (p < 0,01). CONCLUSIONES: El lavado peritoneal con solución de bupivacaína diluida en solución fisiológica fue eficaz para evitar el óbito, por 11 días, en un 100% de los animales con peritonitis fecal.

Background and objective: Acinetobacter baumannii and A. baumannii/calcoaceticus complex are commonly encountered pathogens in nosocomial infections. This study aimed to evaluate the treatment and prognostic risk factors in nosocomial pneumonia caused by these microorganisms. Methods: The study was conducted retrospectively in Uludag University Hospital and included 356 adult non-neutropenic patients with nosocomial pneumonia. Results: Of the subjects, 94.9% (n = 338) had ventilator-associated pneumonia. The clinical response rate was 57.2%, the 14-day mortality 39.6% and the 30-day mortality 53.1%. The significant independent risk factors for the 30-day mortality were severe sepsis (OR, 2.60; 95% CI: 1.49-4.56; P = 0.001), septic shock (OR, 6.12; 95% CI: 2.75-13.64; P < 0.001), APACHE II score >= 20 (OR, 2.12; 95% CI: 1.28-3.50; P = 0.003) and empiric monotherapy (OR, 1.63; 95% CI: 1.00-2.64; P = 0.048). Multi-trauma (OR, 2.50; 95% CI: 1.11-5.68; P = 0.028) was found to be a protective factor. In patients with a clinical pulmonary infection score (CPIS) > 6 on the third day of treatment, both the 14- and 30-day mortality rates were high (P < 0.001, P < 0.001). Also, the 14- and 30-day mortality rates were significantly higher in the patients treated with empiric monotherapy compared with combination therapy (48/93 (51.6%)-46/123 (37.4%), P = 0.037 and 62/93 (66.7%)-65/123 (52.8%), P = 0.041, respectively) in pneumonia caused by imipenem-resistant strains. Conclusion: Mortality rates were high in pneumonia caused by imipenem-resistant A. baumannii or A. baumannii/calcoaceticus complex. In the units with a high level of carbapenem resistance, antibiotic combinations should be considered for empiric therapy.

IncL/M-type plasmids R446b and R471a were originally isolated from Morganella morganii (formerly Proteus morganii) as the first members of the IncL/M group of multidrug resistance (MDR) plasmids ([1][1], [2][2]). IncL/M plasmids are now commonly identified among environmental and clinical isolates

There are a number of effective but highly toxic drugs that exhibit a narrow therapheutic index and marked intersubject pharmacokinetic variability. Optimal therapy with such drugs requires therapeutic drug monitoring (TDM) in order to safely obtain the desired clinical effects. A systematic review was carried out to document the cost-effectiveness of TDM. The Cochrane database and Medline were searched. Reference lists of articles found were searched manually for relevant articles. Very few studies are performed that document the cost-effectiveness of TDM. Only for aminoglycosides it has been demonstrated that TDM is cost-effective. For the other classes of TDM drugs, its rationale has been made plausible, but cost-effectiveness has not been investigated. Since the use of many of these drugs would contain risks of underdosing or overdosing without TDM, emphasis should not be placed on its cost-effectiveness, but rather on how to use it in the most cost-effective and clinically effective manner possible.

There are a number of effective but highly toxic drugs that exhibit a narrow therapeutic index and marked intersubject pharmacokinetic variability. Optimal therapy with such drugs requires therapeutic drug monitoring (TDM) in order to safely obtain the desired clinical effects. A systematic review was carried out to document the cost-effectiveness of TDM. The Cochrane database and Medline were searched. Reference lists of articles found were searched manually for relevant articles. Very few studies are performed that document the cost-effectiveness of TDM. Only for aminoglycosides it has been demonstrated that TDM is cost-effective. For the other classes of TDM drugs, its rationale has been made plausible, but cost-effectiveness has not been investigated. Since the use of many of these drugs would contain risks of underdosing or overdosing without TDM, emphasis should not be placed on its cost-effectiveness, but rather on how to use it in the most cost-effective and clinically effective manner possible.

Drug therapy in cystic fibrosis is focused on pulmonary infection and inflammation, intestinal obstruction and the substitution of pancreas enzymes. Most morbidity and mortality arises from the pulmonary infection and subsequent tissue destruction and deterioration of lung function. Antibiotic treatment is the mainstay of therapy. Nebulised antibiotics improve lung function and the incidence of acute exacerbations is reduced in patients chronically infected with Pseudomonas. Macrolides play a special role probably due to an antiinflammatory effect. Inhalation of rhDNAse improves lung function and decreases deterioration of lung function. New therapeutics directed at the CFTR defect are not yet available. Pharmacokinetics in CF patients may differ from those in healthy volunteers, probably due to differences in body composition.

To the Editor: The blaNDM-1 gene, which produces the New Delhi metallo-β-lactamase (NDM-1) enzyme, confers resistance to the carbapenem class of antimicrobial drugs and can be transferred among different types of bacteria. NDM-1 was identified in 2008 in Sweden from a patient from India who had been hospitalized in New Delhi (1). Since that report, blaNDM-1–positive bacteria have been identified from patients in several countries; most of these patients had a direct link with the Indian subcontinent (2). The spread of blaNDM-1 among bacterial pathogens is of concern not only because of resistance to carbapenems but also because such pathogens typically are resistant to multiple antimicrobial drug classes, which leaves few treatment choices available (3–5). In 2011, spread of blaNDM-1–positive bacteria in an environmental setting in New Delhi was reported (6). The possible appearance of bacteria harboring blaNDM-1 in Vietnam is of concern because cultural and economic links between Vietnam and India are strongly established, including extensive person-to-person exchanges that could enable easy exchange of pathogens. In addition, Vietnam faces a serious problem of antimicrobial drug resistance because drugs are freely available and used in an indiscriminate fashion. Thus, once blaNDM-1–positive bacteria colonize persons in Vietnam, they would be able to spread easily and pose a serious public health threat. During September 2011, we collected paired swab samples (1 for PCR, 1 for culture) of seepage water from 20 sites (rivers, lakes, and water pools in streets) within a 10-km radius of central Hanoi, Vietnam. Samples were transported in Transystem (COPAN Italia S.p.A, Brescia, Italy) to preserve bacteria and DNA. The 20 PCR swab specimens were squeezed out into 0.5-mL volumes of sterile water and centrifuged at 3,000 × g for 30 seconds; 1 μL of the resulting suspension was then used as PCR template to detect blaNDM-1 as described (7). Two samples were positive for blaNDM-1; these 2 samples were collected from the same river (Kim Nguu River) but at sites 3 km apart. To isolate and identify the phenotype and genotype of blaNDM-1–positive bacteria, we repeatedly spread the 20 culture swab specimens onto Muller-Hinton agar (Nissui, Tokyo, Japan) containing 100 mg/L vancomycin (Nakalai, Kyoto, Japan) plus 0.5 mg/L meropenem (LKT Laboratories, St. Paul, MN, USA) until single colonies were obtained. Each colony was then subcultured by plating onto MacConkey agar (Nihon Seiyaku, Tokyo, Japan) containing 0.5 mg/L meropenem to ensure culture purity; colonies were identified by using API 20E strips (bioMerieux, Basingstoke, UK). MICs of these isolates for 13 antimicrobial drugs were calculated by using Etest (bioMerieux), and susceptibility data were interpreted by using Clinical and Laboratory Standards Institute guidelines (www.clsi.org). We harvested several species of bacteria from the 2 seepage samples positive for blaNDM-1: Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, P. fluorescens/putida, and P. luteola. These isolates were placed onto media containing 0.5 mg/L meropenem, and bacterial DNA was extracted and used for the template for PCR analysis to detect blaNDM-1 as described (7). blaNDM-1 was detected in 3 K. pneumoniae isolates from each of the 2 positive samples (6 isolates total); this result was confirmed by sequencing. All 6 isolates were highly resistant to all β-lactam antimicrobial drugs, including carbapenems (Table). To detect another β-lactamase, multiplex PCRs were carried out as described (8); genetic variants blaTEM, blaSHV, blaOXA, blaCTX-M, blaIMP, blaVIM, and blaKPC were not detected in any of the isolates other than K. pneumoniae. All 6 K. pneumoniae isolates were positive for blaTEM and blaCTX-M variants by PCR; these variants were confirmed as blaTEM-1 and blaCTX-M-3 by sequencing. Table Resistance to 13 antimicrobial drugs of blaNDM-1–positive Klebsiella pneumoniae isolates from the Kim Nguu River, Hanoi, Vietnam* Aminoglycosides are often used in the management of severe infectious diseases caused by gram-negative pathogens. 16S rRNA methylases were found to confer high levels of resistance to aminoglycosides such as amikacin, tobramycin, and gentamicin. The 6 K. pneumoniae isolates we found were highly resistant to gentamicin (MIC >1,024 mg/L) and tobramycin (MIC 256–>1,024 mg/L) (Table). Therefore, we screened genetic elements of 16S rRNA methylases (rmtB, rmtC, and armA) by PCR and detected rmtB in all 6 isolates (9). Multilocus sequence typing was applied for these 6 isolates; all were identified as K. pneumoniae sequence type 283 (10), which had not been reported as harboring blaNDM-1. The azide-resistant Escherichia coli strain J53 has been used as recipient for conjugation assay, which had been reported previously (6), but we found no transconjugant strain with blaNDM-1 on MacConkey agar containing 100 mg/L sodium azide and 0.5 mg/L meropenem. Our results show that blaNDM-1–positive K. pneumoniae sequence type 283 is present in the Kim Nguu River, which flows through the central part of Hanoi at 2 sites. The isolates we obtained were also positive for 2 other β-lactamases, blaTEM-1 and blaCTX-M-3, were highly resistant to aminoglycosides related to rmtB, and showed mild elevation of MIC against ciprofloxacin up to 1.5 mg/L. Wide-scale surveillance of environmental and clinical samples in Vietnam and establishment of a strategy to prevent further spread of blaNDM-1 are urgently needed.

23rd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) -- 41394 -- Berlin, GERMANY, WOS: 000338723600006, PubMed ID: 24532009, The purpose of this investigation was to compare the efficacy of colistin-based therapies in extremely drug-resistant Acinetobacter spp. bloodstream infections (XDR-ABSI). A retrospective study was conducted in 27 tertiary-care centers from January 2009 to August 2012. The primary end-point was 14-day survival, and the secondary end-points were clinical and microbiological outcomes. Thirty-six and 214 patients [102 (47.7 %): colistin-carbapenem (CC), 69 (32.2 %): colistin-sulbactam (CS), and 43 (20.1 %: tigecycline): colistin with other agent (CO)] received colistin monotherapy and colistin-based combinations, respectively. Rates of complete response/cure and 14-day survival were relatively higher, and microbiological eradication was significantly higher in the combination group. Also, the in-hospital mortality rate was significantly lower in the combination group. No significant difference was found in the clinical (p = 0.97) and microbiological (p = 0.92) outcomes and 14-day survival rates (p = 0.79) between the three combination groups. Neither the timing of initial effective treatment nor the presence of any concomitant infection was significant between the three groups (p > 0.05) and also for 14-day survival (p > 0.05). Higher Pitt bacteremia score (PBS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Charlson comorbidity index (CCI), and prolonged hospital and intensive care unit (ICU) stay before XDR-ABSI were significant risk factors for 14-day mortality (p = 0.02, p = 0.0001, p = 0.0001, p = 0.02, and p = 0.01, respectively). In the multivariable analysis, PBS, age, and duration of ICU stay were independent risk factors for 14-day mortality (p < 0.0001, p < 0.0001, and p = 0.001, respectively). Colistin-based combination therapy resulted in significantly higher microbiological eradication rates, relatively higher cure and 14-day survival rates, and lower in-hospital mortality compared to colistin monotherapy. CC, CS, and CO combinations for XDR-ABSI did not reveal significant differences with respect to 14-day survival and clinical or microbiological outcome before and after propensity score matching (PSM). PBS, age, and length of ICU stay were independent risk factors for 14-day mortality.

A conjugative IncL/M plasmid (pSEM) conferring resistance to gentamicin, amikacin, kanamycin, sulfonamides, and expanded-spectrum cephalosporins was found in pathogenic strains of Salmonella enterica serotype Typhimurium. Resistance to aminoglycosides was encoded by a sul1 -type class 1 integron (In-t3). An extended-spectrum beta-lactamase gene, bla SHV-5 , was identified 3.5 kb downstream of the integrase ( intI1 ) gene of In-t3. Nucleotide sequence analysis of the 5.3-kb bla SHV-5 –In-t3 region of pSEM highlighted striking similarities with IncL/M plasmids isolated from nosocomial gram-negative pathogens, conferring resistance to expanded-spectrum cephalosporins and aminoglycosides.

The purpose of this study was to report intra- and inter-species spread of carbapenemase genes between gram negative rods isolated from a non-hospitalized patient with bacteremia. The approach included chart review, antibiotic susceptibility testing and phenotypic screening for metallo-ß-lactamase (MBL) detection, PCR and sequencing of bla, aac(6')-Ib and qnr genes, and plasmid analysis by PCR-based replicon typing. The clonal relationships between the isolates were analysed by comparing PFGE profiles. A non-hospitalized patient presented bacteraemia due to wild type Enterobacter cloacae (4.08), a VIM-1-producing E. cloacae (5.08), a VIM-1- and CTX-M-9-producing E. cloacae (7.08), a VIM-2-producing Pseudomonas aeruginosa, and catheter colonization by VIM-1-producing Klebsiella oxytoca. The patient had no previous hospitalization but had recently undergone an ambulatory colonoscopy. In E. cloacae 7.08 and K. oxytoca isolates, the bla VIM-1 gene was located on a transferable plasmid of 48.5 kb, while in E. cloacae 5.08 the bla VIM-1 gene was encoded on a 194 kb non-transferable plasmid. The bla CTX-M-9 gene detected in E. cloacae was encoded on an HI2 plasmid of 290 kb. To date the prevalence of VIM-1 enzymes in the community is low. This molecular finding suggests an intra-species and/or inter-species horizontal spread of the MBL gene in the same non-hospitalized patient. © 2011 Springer-Verlag.

We determined the complete nucleotide sequence of pKOX105, a 54 641 bp plasmid from a Klebsiella oxytoca strain that was isolated from a resident of a long-term-care facility in Bolzano, Italy.The plasmid was sequenced using a shotgun approach. Combinatorial PCRs, directed PCRs and walking reads were used to assemble the contigs and to fill in gaps. Gene sequences were compared with reference plasmids and aligned with GenBank data using BLAST and CLUSTAL W software.pKOX105 belonged to incompatibility group IncN, harboured bla(VIM-1), bla(SHV-12), qnrS1, aacA4 and dfrA14 and conferred resistance to carbapenems, oxyimino-cephalosporins, quinolones, aminoglycosides and trimethoprim. It was highly related to the p9 and p12 plasmids from Klebsiella pneumoniae and K. oxytoca strains isolated at a New York City hospital in 2005 carrying bla(KPC-2) and bla(KPC-3), respectively.IncN plasmids are broad host-range plasmids that have contributed significantly to the worldwide dissemination of many different resistance genes in Enterobacteriaceae from animal and human sources. This plasmid family is now playing a crucial role in the global spread of diverse carbapenemase genes in Klebsiella spp.

Solebo, Colette N/0000-0001-9764-2541 WOS: 000273987200009 PubMed: 19487149 Objectives: Although well-defined principles of rational antimicrobial use are available, inappropriate prescribing patterns are reported worldwide. Accurate information on the usage of antimicrobials, including factors associated with and influencing their use, is valuable for improving the quality of prescription practices. Methods: In this cross-sectional point prevalence survey, data on patients hospitalized in 12 different children's hospitals were collected on a single day. Appropriateness of prescription was compared between the types of antimicrobials prescribed, indications, wards, and presence of/consultation with an infectious disease physician (IDP). Results: A total 711 of 1302 (54.6%) patients evaluated were receiving one or more antimicrobial drugs. The antimicrobial prescription rate was highest in pediatric intensive care (75.7%) and lowest in the surgery wards (37.0%). Of the 711 patients receiving antimicrobials, 332 patients (46.7%) were found to be receiving at least one inappropriately prescribed drug. Inappropriate use was most frequent in surgery wards (80.2%), while it was less common in oncology wards (31.8%; p < 0.001). Respiratory tract infection was the most common indication for antimicrobial use (29.4%). Inappropriate use was more common in deep-seated infections (54.7%) and respiratory infections (56.5%). Fluoroquinolones were used inappropriately more than any other drugs (81.8%, p = 0.021). Consultation with an IDP appears to increase appropriate antimicrobial use (p = 0.008). Conclusions: Inappropriate antimicrobial use remains a common problem in Turkish pediatric hospitals. Consultation with an IDP and prescribing antimicrobial drugs according to microbiological test results could decrease the inappropriate use of antimicrobials. (C) 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Bacteria carry extrachromosomal, self-replicating genetic elements called plasmids. A plasmid is defined as a double-stranded, circular DNA molecule capable of autonomous replication. By definition, plasmids do not carry genes essential for the growth of host cells under nonstressed conditions ([109

Fournier's gangrene (FG) is a rare, rapidly progressive, fulminant form of necrotizing fasciitis of the genital, perianal and perineal regions. Several factors have been reported to contribute to the clinical outcomes. The primary aims of this study were to examine the clinical features of patients with FG and evaluate the predictivity of the Fournier's Gangrene Severity Index (FGSI) score on the outcomes. We carried out a collective retrospective chart review of patients diagnosed and treated for FG in three reference centers between January 1995 and July 2007. Seventy-two patients with FG with were included to the study. Data were collected on medical history, symptoms, physical examination findings, admission and final laboratory tests, timing and extent of surgical debridement and antibiotic therapy. Perianal and perirectal abscess, scrotal abscess and urethral stenosis were the leading etiological factors. Diabetes mellitus was the predominant risk factor. Etiological factors and risk factors did not significantly contribute to survival or mortality, and duration of the symptoms was significantly longer in the non-survivor's group (P < 0.05). The FGSI scores were higher in the non-survivor's group. Regression analysis showed a FGSIS score of 10.5 as the cut-off to the outcome. Based on these results, we conclude that a patient's metabolic status and the extent of disease at presentation are the most important factors determining the prognosis of FG. The FGSI score may be considered as an objective and simple tool to predict the outcome in the patient with FG and should be used in further studies of FG patient series for comparison purposes. © Springer Science+Business Media, B.V. 2008.

A prospective study was designed in order to determine to what extent antibiotics are used in treating community-acquired infections and their costs. Between February and July 2001 a total of 43,011 prescriptions from a representative sample of pharmacies in the city of Denizli (Turkey) were evaluated during the study period. Antibiotics accounted for 16.4% of total prescriptions and 30.8% of the market value of drugs. Penicillins (49.7%), followed by cephalosporins (17.3%), macrolides (9.5%), and aminoglycosides (7.6%) were the most frequently prescribed antibiotics during the study period. The economic burden of antibiotic usage in the community is found higher than in developed countries. In order to reduce this cost the proper use of antibiotics is a matter of urgency.

There are a number of effective but highly toxic drugs that exhibit a narrow therapheutic index and marked intersubject pharmacokinetic variability. Optimal therapy with such drugs requires therapeutic drug monitoring (TDM) in order to safely obtain the desired clinical effects. A systematic review was carried out to document the cost-effectiveness of TDM. The Cochrane database and Medline were searched. Reference lists of articles found were searched manually for relevant articles. Very few studies are performed that document the cost-effectiveness of TDM. Only for aminoglycosides it has been demonstrated that TDM is cost-effective. For the other classes of TDM drugs, its rationale has been made plausible, but cost-effectiveness has not been investigated. Since the use of many of these drugs would contain risks of underdosing or overdosing without TDM, emphasis should not be placed on its cost-effectiveness, but rather on how to use it in the most cost-effective and clinically effective manner possible.

There are a number of effective but highly toxic drugs that exhibit a narrow therapeutic index and marked intersubject pharmacokinetic variability. Optimal therapy with such drugs requires therapeutic drug monitoring (TDM) in order to safely obtain the desired clinical effects. A systematic review was carried out to document the cost-effectiveness of TDM. The Cochrane database and Medline were searched. Reference lists of articles found were searched manually for relevant articles. Very few studies are performed that document the cost-effectiveness of TDM. Only for aminoglycosides it has been demonstrated that TDM is cost-effective. For the other classes of TDM drugs, its rationale has been made plausible, but cost-effectiveness has not been investigated. Since the use of many of these drugs would contain risks of underdosing or overdosing without TDM, emphasis should not be placed on its cost-effectiveness, but rather on how to use it in the most cost-effective and clinically effective manner possible.

Biochemical, histopathological and cell culture evaluations compared the nephrotoxicity of cefazolin with that of gentamicin. New Zealand rabbits were dosed with 250 mg cefazolin/animal im twice daily, 3 mg gentamicin/kg im twice daily, or 0.9% NaCl solution for 10 d. The rabbits in drug-treated groups had necrosis of proximal kidney tubules and elevated urinary-gamma glutamyl transferase (uGGT) levels. The results of the histopathological examinations, uGGT analyses and effects in cell culture indicated the nephrotoxicities of both antibiotics were similar.

Background: Multi-drug resistant forms of Pseudomonas aeruginosa (MDRPA) are a major source of nosocomial infections and when discharged into streams and rivers from hospital wastewater treatment plants (HWWTP) they are known to be able to persist for extended periods. In the city of Manaus (Western Brazilian Amazon), the effluent of three HWWTPs feed into the urban Mindu stream which crosses the city from its rainforest source before draining into the Rio Negro. The stream is routinely used by Manaus residents for bathing and cleaning (of clothes as well as domestic utensils) and, during periods of flooding, can contaminate wells used for drinking water. Results: 16S rRNA metagenomic sequence analysis of 293 cloned PCR fragments, detected an abundance of Pseudomonas aeruginosa (P. aeruginosa) at the stream's Rio Negro drainage site, but failed to detect it at the stream's source. An array of antimicrobial resistance profiles and resistance to all 14 tested antimicrobials was detected among P. aeruginosa cultures prepared from wastewater samples taken from water entering and being discharged from a Manaus HWWTP. Just one P. aeruginosa antimicrobial resistance profile, however, was detected from cultures made from Mindu stream isolates. Comparisons made between P. aeruginosa isolates' genomic DNA restriction enzyme digest fingerprints, failed to determine if any of the P. aeruginosa found in the Mindu stream were of HWWTP origin, but suggested that Mindu stream P. aeruginosa are from diverse origins. Culturing experiments also showed that P. aeruginosa biofilm formation and the extent of biofilm formation produced were both significantly higher in multi drug resistant forms of P. aeruginosa. Conclusions: Our results show that a diverse range of MDRPA are being discharged in an urban stream from a HWWTP in Manaus and that P. aeruginosa strains with ampicillin and amikacin can persist well within it. © 2016 The Author(s).

Background To investigate a possible role of Cefditoren, a recently marketed in Greece third-generation oral cephalosporin in urinary infections of outpatients. Methods During a multicenter survey of Enterobacteriaceae causing UTIs in outpatients during 2005–2007, Cefditoren MICs were determined by agar dilution method in a randomly selected sample of uropathogens. Susceptibility against 18 other oral/parenteral antimicrobials was determined according to Clinical and Laboratory Standards Institute methodology. Results A total of 563 isolates (330 Escherichia coli, 142 Proteus mirabilis and 91 Klebsiella spp) was studied; MIC50/MIC90 of Cefditoren was 0.25/0.5 mg/L respectively, with 97.1% of the isolates being inhibited at 1 mg/L. All 12 strains producing ESBLs or AmpC enzymes were resistant to cefditoren. Susceptibility rates (%) for amoxicillin/clavulanic acid, cefuroxime axetil, cefotaxime, ciprofloxacin, trimethoprim/sulfamethoxazole and fosfomycin were 93.1- 94.1- 96.8-93.1-71.9 and 92.8% respectively. Cefditoren MIC was significantly higher in nalidixic/ciprofloxacin non-susceptible strains; resistance to cefditoren was not associated with resistance to mecillinam, fosfomycin nitrofurantoin and aminoglycosides. Multivariate analysis demonstrated history of urinary infection in the last two weeks or three months as risk factors for cefditoren resistance. Conclusions Cefditoren exhibited enhanced in vitro activity against the most common uropathogens in the outpatient setting, representing an alternative oral treatment option in patients with risk factors for resistance to first-line antibiotics.