Next Issue
Previous Issue

Table of Contents

Antibiotics, Volume 2, Issue 1 (March 2013), Pages 1-181

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
View options order results:
result details:
Displaying articles 1-10
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle Efficacy and Safety of Procalcitonin-Guided Antibiotic Therapy in Lower Respiratory Tract Infections
Antibiotics 2013, 2(1), 1-10; doi:10.3390/antibiotics2010001
Received: 2 November 2012 / Revised: 8 January 2013 / Accepted: 16 January 2013 / Published: 22 January 2013
Cited by 2 | PDF Full-text (915 KB) | HTML Full-text | XML Full-text
Abstract
Background: In 14 randomized controlled studies to date, a procalcitonin (PCT)-based algorithm has been proven to markedly reduce the use of antibiotics along with an unimpaired high safety and low complication rates in patients with lower respiratory tract infections (LRTIs). However, compliance [...] Read more.
Background: In 14 randomized controlled studies to date, a procalcitonin (PCT)-based algorithm has been proven to markedly reduce the use of antibiotics along with an unimpaired high safety and low complication rates in patients with lower respiratory tract infections (LRTIs). However, compliance with the algorithm and safety out of controlled study conditions has not yet been sufficiently investigated. Methods: We performed a prospective international multicenter observational post-study surveillance of consecutive adults with community-acquired LRTI in 14 centers (Switzerland (n = 10), France (n = 3) and the United States (n = 1)). Results: Between September 2009 and November 2010, 1,759 patients were enrolled (median age 71; female sex 44.4%). 1,520 (86.4%) patients had a final diagnosis of LRTI (community-acquired pneumonia (CAP), 53.7%; acute exacerbation of chronic obstructive pulmonary disease (AECOPD), 17.1%; and acute bronchitis, 14.4%). Compliance with the PCT-guided therapy (overall 68.2%) was highest in patients with bronchitis (81.0% vs. AECOPD, 70.1%; CAP, 63.7%; p < 0.001), outpatients (86.1% vs. inpatients, 65.9%; p < 0.001) and algorithm-experienced centers (82.5% vs. algorithm-naive, 60.1%; p < 0.001) and showed significant geographical differences. The initial decision about the antibiotic therapy was based on PCT value in 72.4%. In another 8.6% of patients, antibiotics were administered despite low PCT values but according to predefined criteria. Thus, the algorithm was followed in 81.0% of patients. In a multivariable Cox hazard ratio model, longer antibiotic therapy duration was associated with algorithm-non-compliance, country, hospitalization, CAP vs. bronchitis, renal failure and algorithm-naïvety of the study center. In a multivariable logistic regression complications (death, empyema, ICU treatment, mechanical ventilation, relapse, and antibiotic-associated side effects) were significantly associated with increasing CURB65-Score, CAP vs. bronchitis, multilobar pneumonia, but not with algorithm-compliance. Discussion: Cultural and geographic differences in antibiotic prescribing affected the compliance with our PCT-guided algorithm. Efforts to reinforce compliance are needed. Antibiotic stewardship with PCT is possible, effective and safe without increasing the risk of complications in real-life conditions. Full article
(This article belongs to the Special Issue Antibiotics and Respiratory Tract Infections)
Open AccessArticle The Staphylococcus aureus Membrane Protein SA2056 Interacts with Peptidoglycan Synthesis Enzymes
Antibiotics 2013, 2(1), 11-27; doi:10.3390/antibiotics2010011
Received: 24 December 2012 / Revised: 16 January 2013 / Accepted: 16 January 2013 / Published: 22 January 2013
PDF Full-text (669 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The yet uncharacterized membrane protein SA2056 belongs to the ubiquitous RND (Resistance-Nodulation-cell Division) family of transmembrane efflux transporters. The sa2056 gene is located downstream of femX, the gene encoding the essential, non-ribosomal peptidyl-transferase adding the first glycine in the staphylococcal cell [...] Read more.
The yet uncharacterized membrane protein SA2056 belongs to the ubiquitous RND (Resistance-Nodulation-cell Division) family of transmembrane efflux transporters. The sa2056 gene is located downstream of femX, the gene encoding the essential, non-ribosomal peptidyl-transferase adding the first glycine in the staphylococcal cell wall pentaglycine interpeptide. Due to its proximity to and weak co-transcription with femX, we assumed that sa2056 may somehow be involved in peptidoglycan synthesis. Specific antibodies against SA2056 showed that this protein is expressed during growth and present in the membrane fraction of cell preparations. Using a bacterial two hybrid system, SA2056 was shown to interact (i) with itself, (ii) with FemB, which adds glycines 4 and 5 to the peptidoglycan interpeptide and (iii) with the essential penicillin binding proteins, PBP1 and PBP2, required for cell division and incorporation of the peptidoglycan into the cell wall. Unexpectedly, deletion of sa2056 led to no phenotype regarding growth, antibiotic resistances or cell morphology; nor did sa2056 deletion in combination with femB inactivation alter b-lactam and lysostaphin sensitivity and resistance, respectively, pointing to possible redundancy in the cell wall synthesis pathway. These results suggest an accessory role of SA2056 in S. aureus peptidoglycan synthesis, broadening the range of biological functions of RND proteins. Full article
Open AccessArticle Determination of the Presence of Three Antimicrobials in Surface Water Collected from Urban and Rural Areas
Antibiotics 2013, 2(1), 46-57; doi:10.3390/antibiotics2010046
Received: 3 December 2012 / Revised: 1 February 2013 / Accepted: 4 February 2013 / Published: 7 February 2013
Cited by 7 | PDF Full-text (399 KB) | HTML Full-text | XML Full-text
Abstract
Due to the continuous release of antimicrobials into the environment, the aim of this study was to compare the frequency of detection of sulfamethazine, sulfamethoxypyridazine and trimethoprim in surface water collected from urban and rural areas in Northwestern Spain. A monitoring study [...] Read more.
Due to the continuous release of antimicrobials into the environment, the aim of this study was to compare the frequency of detection of sulfamethazine, sulfamethoxypyridazine and trimethoprim in surface water collected from urban and rural areas in Northwestern Spain. A monitoring study was conducted with 314 river water samples analyzed by high-performance liquid chromatography coupled to tandem mass spectrometry. The results indicated that 37% of the samples contained residues of at least one of the investigated antimicrobials, and every sampling site yielded positive samples. At sites located near the discharge points of wastewater treatment plants and near the collection point of a drinking-water treatment plant, more than 6% of the samples were positive for the presence of antimicrobial residues. Full article
(This article belongs to the Special Issue The Environmental Footprint of Antibiotics)
Figures

Open AccessArticle Virulence of Acinetobacter baumannii Exhibiting Phenotypic Heterogeneous Growth against Meropenem in a Murine Thigh Infection Model
Antibiotics 2013, 2(1), 73-82; doi:10.3390/antibiotics2010073
Received: 14 January 2013 / Revised: 16 February 2013 / Accepted: 1 March 2013 / Published: 11 March 2013
PDF Full-text (330 KB) | HTML Full-text | XML Full-text
Abstract
Acinetobacter baumannii may exhibit phenotypic heterogeneous growth under exposure to antibiotics. We investigated the in vitro characteristics of A. baumannii isolates grown heterogeneously in the presence of meropenem and their virulence evaluated in experimental infections treated with meropenem. Five clinical A. baumannii [...] Read more.
Acinetobacter baumannii may exhibit phenotypic heterogeneous growth under exposure to antibiotics. We investigated the in vitro characteristics of A. baumannii isolates grown heterogeneously in the presence of meropenem and their virulence evaluated in experimental infections treated with meropenem. Five clinical A. baumannii isolates and the respective heterogeneously grown subpopulations were tested by agar dilution minimum inhibitory concentration (MIC) testing, pulsed field gel electrophoresis (PFGE), population analysis using meropenem and growth curves. The virulence of isolates and the therapeutic efficacy of three meropenem dosing schemes was evaluated in a neutropenic murine thigh infection model. The clinical isolates were meropenem-susceptible (MICs 1 to 4 mg/liter) and exhibited three distinct PFGE patterns. In all clinical isolates, population analysis yielded heterogeneously grown colonies. After seven subcultures in antibiotic-free media, resistant MIC levels were retained in two isolates (heteroresistant), while three isolates were reversed to susceptible MICs (persisters). Clinical isolates and heterogeneous subpopulations had similar growth rates. The heterogeneously grown A. baumannii subpopulations had reduced virulence, killing considerably fewer animals than the respective clinical isolates without treatment. The meropenem treatment outcome was similar in infections caused by the clinical and the heterogeneous isolates, irrespective to their MICs. In vitro meropenem exposure induces phenotypic heterogeneous growth in A. baumannii. Compared with the parental clinical isolates, the heterogeneously grown subpopulations exhibited lower virulence, killing fewer mice and responding equally to meropenem treatment, despite their higher MICs. Full article
Open AccessArticle Resistance to Antimicrobials Mediated by Efflux Pumps in Staphylococcus aureus
Antibiotics 2013, 2(1), 83-99; doi:10.3390/antibiotics2010083
Received: 15 January 2013 / Revised: 4 March 2013 / Accepted: 5 March 2013 / Published: 13 March 2013
Cited by 4 | PDF Full-text (575 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Resistance mediated by efflux has been recognized in Staphylococcus aureus in the last few decades, although its clinical relevance has only been recognized recently. The existence of only a few studies on the individual and overall contribution of efflux to resistance phenotypes [...] Read more.
Resistance mediated by efflux has been recognized in Staphylococcus aureus in the last few decades, although its clinical relevance has only been recognized recently. The existence of only a few studies on the individual and overall contribution of efflux to resistance phenotypes associated with the need of well-established methods to assess efflux activity in clinical isolates contributes greatly to the lack of solid knowledge of this mechanism in S. aureus. This study aims to provide information on approaches useful to the assessment and characterization of efflux activity, as well as contributing to our understanding of the role of efflux to phenotypes of antibiotic resistance and biocide tolerance in S. aureus clinical isolates. The results described show that efflux is an important contributor to fluoroquinolone resistance in S. aureus and suggest it as a major mechanism in the early stages of resistance development. We also show that efflux plays an important role on the reduced susceptibility to biocides in S. aureus, strengthening the importance of this long neglected resistance mechanism to the persistence and proliferation of antibiotic/biocide-resistant S. aureus in the hospital environment. Full article
Open AccessArticle An Environmental Risk Assessment for Human-Use Trimethoprim in European Surface Waters
Antibiotics 2013, 2(1), 115-162; doi:10.3390/antibiotics2010115
Received: 23 November 2012 / Revised: 10 January 2013 / Accepted: 14 January 2013 / Published: 18 March 2013
Cited by 11 | PDF Full-text (1545 KB) | HTML Full-text | XML Full-text
Abstract
An environmental risk assessment (ERA) for the aquatic compartment in Europe from human use was developed for the old antibiotic Trimethoprim (TMP), comparing exposure and effects. The exposure assessment is based on European risk assessment default values on one hand and is [...] Read more.
An environmental risk assessment (ERA) for the aquatic compartment in Europe from human use was developed for the old antibiotic Trimethoprim (TMP), comparing exposure and effects. The exposure assessment is based on European risk assessment default values on one hand and is refined with documented human use figures in Western Europe from IMS Health and measured removal in wastewater treatment on the other. The resulting predicted environmental concentrations (PECs) are compared with measured environmental concentrations (MECs) from Europe, based on a large dataset incorporating more than 1800 single MECs. On the effects side, available chronic ecotoxicity data from the literature were complemented by additional, new chronic results for fish and other organisms. Based on these data, chronic-based deterministic predicted no effect concentrations (PNECs) were derived as well as two different probabilistic PNEC ranges. The ERA compares surface water PECs and MECs with aquatic PNECs for TMP. Based on all the risk characterization ratios (PEC÷PNEC as well as MEC÷PNEC) and risk graphs, there is no significant risk to surface waters. Full article
(This article belongs to the Special Issue The Environmental Footprint of Antibiotics)

Review

Jump to: Research

Open AccessReview Recent Advances in Multi-Drug Resistance (MDR) Efflux Pump Inhibitors of Gram-Positive Bacteria S. aureus
Antibiotics 2013, 2(1), 28-45; doi:10.3390/antibiotics2010028
Received: 4 January 2013 / Revised: 29 January 2013 / Accepted: 30 January 2013 / Published: 5 February 2013
Cited by 15 | PDF Full-text (464 KB) | HTML Full-text | XML Full-text
Abstract
The paper focuses on recent achievements in the search for new chemical compounds able to inhibit multidrug resistance (MDR) mechanisms in Gram-positive pathogens. An analysis of the results of the search for new efflux pump inhibitors (EPIs) for Gram-positive bacteria, which [...] Read more.
The paper focuses on recent achievements in the search for new chemical compounds able to inhibit multidrug resistance (MDR) mechanisms in Gram-positive pathogens. An analysis of the results of the search for new efflux pump inhibitors (EPIs) for Gram-positive bacteria, which have been performed over the last decade, indicates that almost all efforts are focused on the NorA (MFS) efflux pump in S. aureus. Considering the chemical structures of the NorA EPIs that have been identified, it can be observed that the most active agents belong to the families of compounds possessing conjugated double bonds, e.g., chalcones, piperine-like compounds, N-cinnamoylphenalkylamides or citral amide derivatives. Indole-, dihydronaphthyl-, 2-chloro-5-bromo-phenyl- or piperidine moieties seem to be profitable for the EPI properties, as well. These results, together with an increasing knowledge about a variety of efflux pumps that are involved in MDR of Gram-positive pathogens underline that further search for new EPIs should pay more attention to develop MDR efflux protein targets, including SMR, MATE, ABC or other members of the MFS family. Full article
Open AccessReview Role of Phenothiazines and Structurally Similar Compounds of Plant Origin in the Fight against Infections by Drug Resistant Bacteria
Antibiotics 2013, 2(1), 58-72; doi:10.3390/antibiotics2010058
Received: 26 December 2012 / Revised: 28 January 2013 / Accepted: 31 January 2013 / Published: 18 February 2013
Cited by 5 | PDF Full-text (358 KB) | HTML Full-text | XML Full-text
Abstract
Phenothiazines have their primary effects on the plasma membranes of prokaryotes and eukaryotes. Among the components of the prokaryotic plasma membrane affected are efflux pumps, their energy sources and energy providing enzymes, such as ATPase, and genes that regulate and code for [...] Read more.
Phenothiazines have their primary effects on the plasma membranes of prokaryotes and eukaryotes. Among the components of the prokaryotic plasma membrane affected are efflux pumps, their energy sources and energy providing enzymes, such as ATPase, and genes that regulate and code for the permeability aspect of a bacterium. The response of multidrug and extensively drug resistant tuberculosis to phenothiazines shows an alternative therapy for the treatment of these dreaded diseases, which are claiming more and more lives every year throughout the world. Many phenothiazines have shown synergistic activity with several antibiotics thereby lowering the doses of antibiotics administered to patients suffering from specific bacterial infections. Trimeprazine is synergistic with trimethoprim. Flupenthixol (Fp) has been found to be synergistic with penicillin and chlorpromazine (CPZ); in addition, some antibiotics are also synergistic. Along with the antibacterial action described in this review, many phenothiazines possess plasmid curing activities, which render the bacterial carrier of the plasmid sensitive to antibiotics. Thus, simultaneous applications of a phenothiazine like TZ would not only act as an additional antibacterial agent but also would help to eliminate drug resistant plasmid from the infectious bacterial cells. Full article
Open AccessReview Bacterial Responses and Genome Instability Induced by Subinhibitory Concentrations of Antibiotics
Antibiotics 2013, 2(1), 100-114; doi:10.3390/antibiotics2010100
Received: 8 February 2013 / Revised: 4 March 2013 / Accepted: 5 March 2013 / Published: 14 March 2013
Cited by 8 | PDF Full-text (433 KB) | HTML Full-text | XML Full-text
Abstract
Nowadays, the emergence and spread of antibiotic resistance have become an utmost medical and economical problem. It has also become evident that subinhibitory concentrations of antibiotics, which pollute all kind of terrestrial and aquatic environments, have a non-negligible effect on the evolution [...] Read more.
Nowadays, the emergence and spread of antibiotic resistance have become an utmost medical and economical problem. It has also become evident that subinhibitory concentrations of antibiotics, which pollute all kind of terrestrial and aquatic environments, have a non-negligible effect on the evolution of antibiotic resistance in bacterial populations. Subinhibitory concentrations of antibiotics have a strong effect on mutation rates, horizontal gene transfer and biofilm formation, which may all contribute to the emergence and spread of antibiotic resistance. Therefore, the molecular mechanisms and the evolutionary pressures shaping the bacterial responses to subinhibitory concentrations of antibiotics merit to be extensively studied. Such knowledge is valuable for the development of strategies to increase the efficacy of antibiotic treatments and to extend the lifetime of antibiotics used in therapy by slowing down the emergence of antibiotic resistance. Full article
(This article belongs to the Special Issue Antibiotic Resistance)
Open AccessReview Resistance-Nodulation-Division Multidrug Efflux Pumps in Gram-Negative Bacteria: Role in Virulence
Antibiotics 2013, 2(1), 163-181; doi:10.3390/antibiotics2010163
Received: 28 December 2012 / Revised: 5 March 2013 / Accepted: 11 March 2013 / Published: 18 March 2013
Cited by 6 | PDF Full-text (377 KB) | HTML Full-text | XML Full-text
Abstract
Resistance-Nodulation-Division (RND) efflux pumps are one of the most important determinants of multidrug resistance (MDR) in Gram-negative bacteria. With an ever increasing number of Gram-negative clinical isolates exhibiting MDR phenotypes as a result of the activity of RND pumps, it is clear [...] Read more.
Resistance-Nodulation-Division (RND) efflux pumps are one of the most important determinants of multidrug resistance (MDR) in Gram-negative bacteria. With an ever increasing number of Gram-negative clinical isolates exhibiting MDR phenotypes as a result of the activity of RND pumps, it is clear that the design of novel effective clinical strategies against such pathogens must be grounded in a better understanding of these pumps, including their physiological roles. To this end, recent evidence suggests that RND pumps play an important role in the virulence of Gram-negative pathogens. In this review, we discuss the important role RND efflux pumps play in different facets of virulence including colonization, evasion of host defense mechanisms, and biofilm formation. These studies provide key insights that may ultimately be applied towards strategies used in the design of effective therapeutics against MDR Gram negative bacterial pathogens. Full article

Journal Contact

MDPI AG
Antibiotics Editorial Office
St. Alban-Anlage 66, 4052 Basel, Switzerland
antibiotics@mdpi.com
Tel. +41 61 683 77 34
Fax: +41 61 302 89 18
Editorial Board
Contact Details Submit to Antibiotics
Back to Top