Think (Gram) negative!

The increasing prevalence of multiresistant Gram-negative bacteria of the Enterobacteriaceae family in Europe is a worrisome phenomenon. Extended spectrum betalactamase-producing Escherichia coli strains are widespread in the community and are frequently imported into the hospital. Of even more concern is the spread of carbapenem-resistant strains of Klebsiella spp. from regions where they are already endemic. Antibiotic use is a main driver of antibiotic resistance, which again increases broad spectrum antibiotic use, resulting in a vicious circle that is difficult to interrupt. The present commentary highlights important findings of a surveillance study of antimicrobial use and resistance in German ICUs over 8 years with a focus on Gram-negative resistance

Klonierung und Charakterisierung der Caseinkinase-1a aus Neurospora crassa

Das Uhrenprotein Frequency (FRQ) wird in Neurospora crassa nach seiner Synthese phosphoryliert. Die dafür verantwortliche(n) Kinase(n) ist (sind) nicht identifiziert. In der Fruchtfliege Drosophila melanogaster und im Goldhamster Mesocricetus auratus werden Uhrenproteine durch Enzyme aus der Familie der Caseinkinasen 1 phosphoryliert (Doubletime, tau-Genprodukt). Im Rahmen dieser Arbeit konnte die zur humanen Caseinkinase 1ε und zu Doubletime (DBT) aus D. melanogaster homologe CK-1a aus N. crassa kloniert und charakterisiert werden. Es wurde auch eine zweite zur humanen Caseinkinase 1ε homologe Kinase - CK-1b - in N. crassa identifiziert. Das für CK-1a kodierende Gen ist näher mit DBT verwandt. Daher wurde CK-1a in E. coli als Hexahistidinfusionsprotein kloniert, exprimiert und gereinigt. Die gereinigte CK-1a ist in vitro aktiv. Sie phosphoryliert β-Casein und unterliegt einer Autophosphorylierung. FRQ wird in vitro an mindestens zwei Stellen von CK-1a phosphoryliert. Diese Phosphorylierungsstellen liegen wahrscheinlich innerhalb der PEST-Sequenzen von FRQ

Impact of the French campaign to reduce inappropriate ambulatory antibiotic use on the prescription and consultation rates for respiratory tract infections

Objectives To assess long-term trends in the volume of ambulatory antibiotic prescriptions and prescription and consultation rates for respiratory tract infections (RTIs) in France in relation to the yearly public antibiotic campaign since 2002. Methods Data collected on representative cohorts of office-based physicians and pharmacies in France participating in IMS Health panels between 1980 and 2009 were analysed retrospectively. Main outcome measures were antibiotic prescriptions per 1000 inhabitants per year (PIY), consultations per 1000 inhabitants per year and proportion of consultations resulting in antibiotic prescriptions. Results The peak in ambulatory antibiotic prescriptions occurred in 1997 (1468 PIY). Although prescriptions had decreased by 6% until 2001, prescriptions fell sharply (−22%) between 2001 and 2004, followed by stable prescription rates until 2009. The 2001-09 decrease in antibiotic prescriptions was driven by a sharp decline in office-based antibiotic prescriptions (−33%), exclusively achieved through a decrease in prescriptions for RTIs. Consultations for RTIs steadily declined between 2001 and 2009 (−23%), with the proportion of consultations resulting in antibiotic prescriptions decreasing from 58% to 46%. Not all types of RTIs were equally affected. The largest decrease in prescriptions was observed for nasopharyngitis and influenza. Rates for bronchitis, sinusitis, otitis media and tonsillitis remained persistently high. Conclusions During its first 3 years, the French public campaign accelerated a pre-existing decrease in ambulatory antibiotic prescriptions. The decrease in consultation rates suggests that altered illness behaviour of patients may have contributed to the observed decline. The persistently high prescribing rates for certain RTIs show that further effort is needed to improve antibiotic prescribing in Franc

Unusual evolution of a non-hacek Gram-negative endocarditis in a patient with Turner syndrome

Non-HACEK Gram-negative endocarditis is a rare but severe illness, and the diagnosis can be difficult to establish. Here, we report the case of a 72-year-old woman with Turner syndrome suffering from non-typhoid Salmonella endocarditis of the triscupid valve, who benefited from prompt antibiotic treatment allowing a quick and complete recover

A PEST-like element in FREQUENCY determines the length of the circadian period in Neurospora crassa

FREQUENCY (FRQ) is a crucial element of the circadian clock in Neurospora crassa. In the course of a circadian day FRQ is successively phosphorylated and degraded. Here we report that two PEST-like elements in FRQ, PEST-1 and PEST-2, are phosphorylated in vitro by recombinant CK-1a and CK-1b, two newly identified Neurospora homologs of casein kinase 1ε. CK-1a is localized in the cytosol and the nuclei of Neurospora and it is in a complex with FRQ in vivo. Deletion of PEST-1 results in hypophosphorylation of FRQ and causes significantly increased protein stability. A strain harboring the mutant frqΔPEST-1 gene shows no rhythmic conidiation. Despite the lack of overt rhythmicity, frqΔPEST-1 RNA and FRQΔPEST-1 protein are rhythmically expressed and oscillate in constant darkness with a circadian period of 28 h. Thus, by deletion of PEST-1 the circadian period is lengthened and overt rhythmicity is dissociated from molecular oscillations of clock components

Drugs of Last Resort? The Use of Polymyxins and Tigecycline at US Veterans Affairs Medical Centers, 2005–2010

Multidrug-resistant (MDR) and carbapenem-resistant (CR) Gram-negative pathogens are becoming increasingly prevalent around the globe. Polymyxins and tigecycline are among the few antibiotics available to treat infections with these bacteria but little is known about the frequency of their use. We therefore aimed to estimate the parenteral use of these two drugs in Veterans Affairs medical centers (VAMCs) and to describe the pathogens associated with their administration. For this purpose we retrospectively analyzed barcode medication administration data of parenteral administrations of polymyxins and tigecycline in 127 acute-care VAMCs between October 2005 and September 2010. Overall, polymyxin and tigecycline use were relatively low at 0.8 days of therapy (DOT)/1000 patient days (PD) and 1.6 DOT/1000PD, respectively. Use varied widely across facilities, but increased overall during the study period. Eight facilities accounted for three-quarters of all polymyxin use. The same statistic for tigecycline use was twenty-six VAMCs. There were 1,081 MDR or CR isolates during 747 hospitalizations associated with polymyxin use (1.4/hospitalization). For tigecycline these number were slightly lower: 671 MDR or CR isolates during 500 hospitalizations (1.3/hospitalization) (p = 0.06). An ecological correlation between the two antibiotics and combined CR and MDR Gram-negative isolates per 1000PD during the study period was also observed (Pearson’s correlation coefficient r = 0.55 polymyxin, r = 0.19 tigecycline). In summary, while polymyxin and tigecycline use is low in most VAMCs, there has been an increase over the study period. Polymyxin use in particular is associated with the presence of MDR Gram-negative pathogens and may be useful as a surveillance measure in the future

Navigating the Web in Search of Resources on Antimicrobial Stewardship in Health Care Institutions

Bacterial resistance to antimicrobials has become a public health threat for which coordinated action at the international, national, and local level is needed. Current recommendations for the control of antimicrobial overuse and resistance in hospitals recommend various strategies, including antimicrobial stewardship programs. Several of these integrated and multidisciplinary antimicrobial management programs provide detailed information and recommendations on the Web. We performed a search of the most relevant and authoritative Web sites in English that were available without need for special registration or cost. The search excluded community-based programs, and we present only established programs or those providing expert information useful for building a hospital-based antimicrobial stewardship program. The overview of these Web sites may be useful either for institutions or individuals planning to implement such programs in their own health care institution or for educational purposes targeted at different professionals involved in improving antimicrobial practic