Antibacterial activity of nonantibiotics is orthogonal to standard antibiotics.

Numerous nonantibiotic drugs have potent antibacterial activity and can adversely affect the human microbiome. The mechanistic underpinning of this toxicity remains largely unknown. We investigated the antibacterial activity of 200 drugs using genetic screens with thousands of barcoded Escherichia coli knockouts. We analyzed 2 million gene-drug interactions underlying drug-specific toxicity. Network-based analysis of drug-drug similarities revealed that antibiotics clustered into modules that are consistent with the mode of action of their established classes, whereas nonantibiotics remained unconnected. Half of the nonantibiotics clustered into separate modules, potentially revealing shared and unexploited targets for new antimicrobials. Analysis of efflux systems revealed that they widely affect antibiotics and nonantibiotics alike, suggesting that the impact of nonantibiotics on antibiotic cross-resistance should be investigated closely in vivo.

Recombinant Myeloperoxidase as a New Class of Antimicrobial Agents.

Heme-containing peroxidases are widely distributed in the animal and plant kingdoms and play an important role in host defense by generating potent oxidants. Myeloperoxidase (MPO), the prototype of heme-containing peroxidases, exists in neutrophils and monocytes. MPO has a broad spectrum of microbial killing. The difficulty of producing MPO at a large scale hinders its study and utilization. This study aimed to overexpress recombinant human MPO and characterize its microbicidal activities in vitro and in vivo. A human HEK293 cell line stably expressing recombinant MPO (rMPO) was established as a component of this study. rMPO was overexpressed and purified for studies on its biochemical and enzymatic properties, as well as its microbicidal activities. In this study, rMPO was secreted into culture medium as a monomer. rMPO revealed enzymatic activity similar to that of native MPO. rMPO, like native MPO, was capable of killing a broad spectrum of microorganisms, including Gram-negative and -positive bacteria and fungi, at low nM levels. Interestingly, rMPO could kill antibiotic-resistant bacteria, making it very useful for treatment of nosocomial infections and mixed infections. The administration of rMPO significantly reduced the morbidity and mortality of murine lung infections induced by Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus. In animal safety tests, the administration of 100 nM rMPO via tail vein did not result in any sign of toxic effects. Taken together, the data suggest that rMPO purified from a stably expressing human cell line is a new class of antimicrobial agents with the ability to kill a broad spectrum of pathogens, including bacteria and fungi with or without drug resistance. IMPORTANCE Over the past 2 decades, more than 20 new infectious diseases have emerged. Unfortunately, novel antimicrobial therapeutics are discovered at much lower rates. Infections caused by resistant microorganisms often fail to respond to conventional treatment, resulting in prolonged illness, greater risk of death, and high health care costs. Currently, this is best seen with the lack of a cure for coronavirus disease 2019 (COVID-19). To combat such untreatable microorganisms, there is an urgent need to discover new classes of antimicrobial agents. Myeloperoxidase (MPO) plays an important role in host defense. The difficulty of producing MPO on a large scale hinders its study and utilization. We have produced recombinant MPO at a large scale and have characterized its antimicrobial activities. Most importantly, recombinant MPO significantly reduced the morbidity and mortality of murine pneumonia induced by Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus. Our data suggest that recombinant MPO from human cells is a new class of antimicrobials with a broad spectrum of activity.

DRAMP 3.0: an enhanced comprehensive data repository of antimicrobial peptides.

Stapled antimicrobial peptides are an emerging class of artificial cyclic peptide molecules which have antimicrobial activity and potent structure stability. We previously published the Data Repository of Antimicrobial Peptides (DRAMP) as a manually annotated and open-access database of antimicrobial peptides (AMPs). In the update of version 3.0, special emphasis was placed on the new development of stapled AMPs, and a subclass of specific AMPs was added to store information on these special chemically modified AMPs. To help design low toxicity AMPs, we also added the cytotoxicity property of AMPs, as well as the expansion of newly discovered AMP data. At present, DRAMP has been expanded and contains 22259 entries (2360 newly added), consisting of 5891 general entries, 16110 patent entries, 77 clinical entries and 181 stapled AMPs. A total of 263 entries have predicted structures, and more than 300 general entries have links to experimentally determined structures in the Protein Data Bank. The update also covers new annotations, statistics, categories, functions and download links. DRAMP is available online at http://dramp.cpu-bioinfor.org/.

Synthesis and characterization of Sophora alopecuroides L. green synthesized of Ag nanoparticles for the antioxidant, antimicrobial and DNA damage prevention activity

Abstract In this study, it was aimed to investigate the amount of antioxidant, protective properties against DNA damage and antibacterial properties against various pathogens after the interaction of Ag metal (Ag NPs/Sa) of Sophora alopecuroides L. (S. alopecuroides L) plant seed, which is grown in Igdir and used in the treatment of many diseases. The DPPH radical quenching activity of Ag NPs/Sa was performed by using Blois method, DNA damage prevention activity by gel electrophoresis and antibacterial property by disk diffusion method. With the green synthesis method, AgNPs obtained as a result of the reaction of the plant and Ag metal are UV visible spectrophotometer (UV-vis), fourier-transformed infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and scanning electron microscope (SEM). DPPH radical quenching activity of Ag NPs/Sa was investigated in the concentration range of 25-250 µg/ml. The radical quenching activity at a concentration of 250 µg/ml was 85,215 ± 0,101%, while this value was 93,018% for the positive control BHA. It has been observed that the protective property of pBR322 plasmid DNA damage against OH radicals originating from H2O2 increases with concentration. It has been observed that Ag NPs/Sa has significant antimicrobial properties against some pathogens (B. subtilis ATCC 6633 E. coli ATCC 25952, B. cereus ATCC 10876, P. aeruginosa ATCC 27853, E. faecalis ATCC 29212, S. aureus ATTC 29213 and C. albicans ATTC 90028) that cause disease and even some pathogens are more effective than antibiotics

A Review on Microbial Products and Their Perspective Application as Antimicrobial Agents.

Microorganisms including actinomycetes, archaea, bacteria, fungi, yeast, and microalgae are an auspicious source of vital bioactive compounds. In this review, the existing research regarding antimicrobial molecules from microorganisms is summarized. The potential antimicrobial compounds from actinomycetes, particularly Streptomyces spp.; archaea; fungi including endophytic, filamentous, and marine-derived fungi, mushroom; and microalgae are briefly described. Furthermore, this review briefly summarizes bacteriocins, halocins, sulfolobicin, etc., that target multiple-drug resistant pathogens and considers next-generation antibiotics. This review highlights the possibility of using microorganisms as an antimicrobial resource for biotechnological, nutraceutical, and pharmaceutical applications. However, more investigations are required to isolate, separate, purify, and characterize these bioactive compounds and transfer these primary drugs into clinically approved antibiotics.

Indwelling Urinary Catheter and Dementia Are Associated with Enterococcal Urinary Tract Infections in Hospitalized Patients.

BACKGROUND: The recent increase in enterococcal urinary tract infections (EUTI) and the potential morbidity and mortality associated with inappropriate antimicrobial treatment underscores the need for early risk assessment and institution of appropriate empirical antimicrobial therapy. OBJECTIVES: To identify high-risk features associated with hospitalized patients with EUTI. METHODS: Demographic, clinical, laboratory, and bacteriological data of 285 patients hospitalized with UTI during 2016 were retrieved from the computerized database of Shamir Medical Center. Patients were divided into two groups: EUTI and non-EUTI (NEUTI), according to the presence or absence of enterococcus in the urine culture. The features of the two groups were compared. RESULTS: We obtained 300 urine cultures from 285 patients. Of the total, 80 patients (26.6%) had EUTI and 220 patients (73.3%) had NEUTI. A higher prevalence of urinary multi-bacterial cultures was found in EUTI compared to NEUTI patients (P < 0.01). Higher prevalence of permanent indwelling urinary catheter and dementia were found in hospitalized patients with community-acquired EUTI and nosocomial EUTI respectively (P = 0.02, P = 0.016) compared to patients with NEUTI. CONCLUSIONS: Indwelling urinary catheter and dementia are risk factors for EUTI in patients with community and hospital acquired infection, respectively.

Are Bacteriocins a Feasible Solution for Current Diverse Global Problems?

The development of effective technologies to cope with persistent and progressive global problems in human health and sustainable development has become an imperative worldwide challenge. The search for natural alternatives has led to the discovery of bacteriocins, which are potent protein antimicrobial compounds produced by most bacteria. The relevance of these molecules is evidenced by more than 4,500 papers published in the last decade in Scopus indexed journals highlighting their versatility and potential to impact various aspects of daily life, including the food industry, medicine, and agriculture. Bacteriocins have demonstrated antibacterial, antifungal, antiviral, and anticancer activities, and they also act as microbiota regulators and plant growth promoters. This mini-review aims to provide insights into the current state and emerging roles of bacteriocins, as well as their potential and limitations as feasible solutions against current diverse global problems.

Recent Advances in the Discovery and Function of Antimicrobial Molecules in Platelets.

The conventional function described for platelets is maintaining vascular integrity. Nevertheless, increasing evidence reveals that platelets can additionally play a crucial role in responding against microorganisms. Activated platelets release molecules with antimicrobial activity. This ability was first demonstrated in rabbit serum after coagulation and later in rabbit platelets stimulated with thrombin. Currently, multiple discoveries have allowed the identification and characterization of PMPs (platelet microbicidal proteins) and opened the way to identify kinocidins and CHDPs (cationic host defense peptides) in human platelets. These molecules are endowed with microbicidal activity through different mechanisms that broaden the platelet participation in normal and pathologic conditions. Therefore, this review aims to integrate the currently described platelet molecules with antimicrobial properties by summarizing the pathways towards their identification, characterization, and functional evaluation that have promoted new avenues for studying platelets based on kinocidins and CHDPs secretion.

A Pilot Study of RNA Sequencing to Improve the Diagnostic Yield of Bronchoalveolar Lavage Specimens in Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients.

BACKGROUND: Pulmonary complications often cause morbidity and mortality in pediatric allogeneic hematopoietic stem cell transplant (HSCT) recipients. While detection of infection and initiation of appropriate antimicrobial therapy improves survival, present techniques oftentimes do not detect infections in bronchoalveolar lavage (BAL) samples because of pretreatment with antimicrobial therapies and the need for a priori knowledge of likely viral pathogens, decreasing the yield of BAL. OBJECTIVE: We evaluated whether RNA-based massively parallel sequencing (MPS) would improve detection of infections in BAL fluid in pediatric allogeneic HSCT recipients. RESULTS: Nine patients underwent 10 BAL (1 patient underwent 2 BAL) and had sufficient BAL fluid for inclusion in this study. Clinical microbiological testing identified infections in 7 patients, and MPS identified infections in 5 patients, although some of these detected organisms were not detected by clinical testing. Results were fully concordant in 5 patients, fully discordant in 3 patients, and partially discordant in 2 patients. Bacterial, viral, and fungal infections were detected via both techniques. CONCLUSION: This suggests that MPS in conjunction with routine clinical testing increases the yield of detection of infectious organisms in the BAL fluid.

ConjuPepDB: a database of peptide-drug conjugates.

Peptide-drug conjugates are organic molecules composed of (i) a small drug molecule, (ii) a peptide and (iii) a linker. The drug molecule is mandatory for the biological action, however, its efficacy can be enhanced by targeted delivery, which often also reduces unwanted side effects. For site-specificity the peptide part is mainly responsible. The linker attaches chemically the drug to the peptide, but it could also be biodegradable which ensures controlled liberation of the small drug. Despite the importance of the field, there is no public comprehensive database on these species. Herein we describe ConjuPepBD, a freely available, fully annotated and manually curated database of peptide drug conjugates. ConjuPepDB contains basic information about the entries, e.g. CAS number. Furthermore, it also implies their biomedical application and the type of chemical conjugation employed. It covers more than 1600 conjugates from ∼230 publications. The web-interface is user-friendly, intuitive, and useable on several devices, e.g. phones, tablets, PCs. The webpage allows the user to search for content using numerous criteria, chemical structure and a help page is also provided. Besides giving quick insight for newcomers, ConjuPepDB is hoped to be also helpful for researchers from various related fields. The database is accessible at: https://conjupepdb.ttk.hu/.

Antimicrobial use in wean to market pigs in the United States assessed via voluntary sharing of proprietary data.

Data on antimicrobial use were collected for the 2016 and 2017 calendar years from swine producers in the United States. Nine large systems, collectively producing over 20 million market pigs annually, voluntarily provided data to advance understanding of antimicrobial use in the industry and to support antimicrobial stewardship initiatives. The scope of the study was limited to growing pigs, and the granularity of data varied across the systems. Data were summarized both qualitatively and quantitatively by antimicrobial class, active ingredient and route of administration (injection, water and feed). Data on the purpose of administration, doses and durations of administration were not available, but some information was provided by the responsible veterinarians. Aggregate data were similar both qualitatively and quantitatively in 2016 and 2017, although marked changes between years were evident within systems for some antimicrobials. Antimicrobial use (by weight) was dominated by the tetracycline class (approximately 60% of total use). Antimicrobials in classes categorized as critically important constituted 4.5% and 5.3% of total use in 2016 and 2017, respectively. In both years, fluoroquinolone (0.23%, 0.46%) and 3rd generation cephalosporin (0.15%, 0.11%) use collectively accounted for <1% of total use. Administration was predominantly oral in feed and water, and injection comprised approximately 2% of use overall, but around 12% for critically important antimicrobials. There was considerable variability among systems in patterns of antimicrobial use. This pilot project demonstrates the feasibility of acquiring antimicrobial use data via voluntary sharing. It is currently being expanded among larger swine production systems, and further efforts to enable confidential data sharing and benchmarking for smaller producers are being pursued by the swine industry. Recognized biases in the data caution against over-interpretation of these data as an index of national use.

Oral treatment of acute pyelonephritis: when, with which antimicrobial agent and for how long? / Tratamiento oral de la pielonefritis aguda: ¿cuándo, con qué antimicrobiano y durante cuánto tiempo?

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Use of antimicrobials in beef cattle: an observational study in the north of Italy.

Antimicrobial resistance is a worldwide issue whereby a more prudent use of medications is needed, especially for those antimicrobials (AM) classified as 'highest priority critically important antimicrobials' (HPCIAs) which are likely contributors to the development of resistance. So far, data on antimicrobial use (AMU) in EU are mainly reported at sales level while information on real use, mostly in beef production, is poor. The most reliable indicator to measure AMU is the treatment incidence (TI100) calculated by using the Defined Daily Dose Animal (DDDA) as stated by the European Medicines Agency (EMA). Although Italy ranks second among EU countries with regard to the AM sales in livestock production, data on AMU of the Italian beef production is still lacking, whereby the aim of this study was to provide information on the current scenario of AMU in Italian beef cattle. Data were collected from January 2016 to April 2019 from specialized beef fattening farms located in the north of Italy yielding a final dataset of 1376 batches. Data on performance and AM agents used in the study were collected and TI100 indexes per batch were calculated according to both Italian and EMA's DDDA. A Kruskal-Wallis test was used to check for differences between years and seasons. Results showed a significant variation between years and seasons with a reduction of TI100 based on Italian DDDA as time progressed (P < 0.05). However, about 40% of the total amount of treatments administered were HPCIAs with macrolides accounting for the 27.7% of the total amount. The most common reasons of administration of AM were respiratory diseases (68.9%) and lameness (17.6%). Penicillins was the class of AM used on the highest proportion of batches (84.4%) showing that broad-spectrum AM were widely exploited among herds. In summary, despite a general reduction of AMU in beef cattle over time, a great use of HPCIAs was still observed suggesting that AM stewardship for Italian beef production should pay particular emphasis on the reduction of HPCIAs use. This shows how overall knowledge on where efforts need to be optimized is important to develop targeted strategies for a more responsible AM stewardship. Results of the current study may also contribute to define national and EU benchmark criteria for AMU, as a comparison with studies carried out in other countries or on other food-producing sectors is still challenging to achieve.

Possible therapeutic agents for COVID-19: a comprehensive review.

INTRODUCTION: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged in China. There are no available vaccines or antiviral drugs for COVID-19 patients. Herein, we represented possible therapeutic agents that may stand as a potential therapy against COVID-19. AREAS COVERED: We searched PubMed, Google Scholar, and clinicaltrials.gov for relevant papers. We showed some agents with potentially favorable efficacy, acceptable safety as well as good pharmacokinetic profiles. Several therapies are under assessment to evaluate their efficacy and safety for COVID-19. However, some drugs were withdrawn due to their side effects after demonstrating some clinical efficacy. Indeed, the most effective therapies could be organ function support, convalescent plasma, anticoagulants, and immune as well as antiviral therapies, especially anti-influenza drugs due to the similarities between respiratory viruses regarding viral entry, uncoating, and replication. We encourage giving more attention to favipiravir, remdesivir, and measles vaccine. EXPERT OPINION: A combination, at least dual or even triple therapy, of the aforementioned efficacious and safe therapies is greatly recommended for COVID-19. Further, patients should have a routine assessment for their coagulation and bleeding profiles as well as their inflammatory and cytokine concentrations.

Bovine Respiratory Disease Treatment Failure: Impact and Potential Causes.

Bovine respiratory disease (BRD) is often attributed to complex interactions between the host, pathogen, and the environment. Likewise, many BRD treatment failures result from interactions between the host, pathogen, environment, drug, and drug administrator. Investigating and addressing the underlying causes of BRD treatment failures can improve clinical outcomes and animal welfare of future cases, improve morale of employees, reduce direct costs of dealing with BRD treatment failures, refine antimicrobial prescribing practices, and advance antimicrobial stewardship. This article discusses these interactions and provides guidance to veterinary practitioners on evaluating the success of treatment protocols.

Antimicrobial usage at a large teaching hospital in Lusaka, Zambia.

Antimicrobial resistance is a growing global health concern. Antimicrobial stewardship (AMS) curbs resistance rates by encouraging rational antimicrobial use. However, data on antimicrobial stewardship in developing countries is scarce. The objective of this study was to characterize antimicrobial use at the University Teaching Hospital (UTH) in Lusaka, Zambia as a guiding step in the development of an AMS program. This was a cross-sectional, observational study evaluating antimicrobial appropriateness and consumption in non-critically ill adult medicine patients admitted to UTH. Appropriateness was defined as a composite measure based upon daily chart review. Sixty percent (88/146) of all adult patients admitted to the general wards had at least one antimicrobial ordered and were included in this study. The most commonly treated infectious diseases were tuberculosis, pneumonia, and septicemia. Treatment of drug sensitive tuberculosis is standardized in a four-drug combination pill of rifampicin, isoniazid, pyrazinamide and ethambutol, therefore appropriateness of therapy was not further evaluated. The most common antimicrobials ordered were cefotaxime (n = 45), ceftriaxone (n = 28), and metronidazole (n = 14). Overall, 67% of antimicrobial orders were inappropriately prescribed to some extent, largely driven by incorrect dose or frequency in patients with renal dysfunction. Antimicrobial prescribing among hospitalized patients at UTH is common and there is room for optimization of a majority of antimicrobial orders. Availability of certain antimicrobials must be taken into consideration during AMS program development.

Considerations for application of biopharmaceutics classification system in chicken: Exemplified by seven drugs classification.

Biopharmaceutics Classification System (BCS) has gained broad acceptance in promoting the development of human drugs. To date, the applicability of existing human BCS criteria has not been evaluated in chickens. The objective of this study was to discuss the feasibility of BCS extrapolation between species and establish a preliminary chicken BCS by classifying seven veterinary commonly used drugs including metronidazole, amoxicillin, sulfamethoxazole, sulfadiazine, ciprofloxacin hydrochloride, doxycycline hydrochloride, and trimethoprim. Firstly, we finished the determination of physiological parameters affecting solubility in chickens, including body temperature, gastrointestinal pH, and the fluid volume in the gastrointestinal tract (GI), and the drug is considered highly soluble in chicken BCS when the highest dose strength is soluble in 20.40 ml (fed) or 6.73 ml (fasted) over the pH range of 1-8 at 41°C. Drug solubility classification was based on dose number calculation. Metronidazol and amoxicillin were classed differently under fed and fasted conditions. Secondly, we discussed the effect of ABC transporters (MDCK vs. MDCK-chAbcb1/Abcg2) and pH (5.5 vs. 7.4) on drug permeability and classification. The drug is classified as highly permeable when its permeability is equal to or greater than metoprolol tartrate. Though ABC transporters and pH significantly affected the permeability values of drugs (p < .05), the permeability classification of the drugs has not been changed except for sulfamethoxazole. This work highlights some of the significant challenges that would be encountered in order to develop a chicken BCS, this valuable information could serve as a helpful tool during chicken drugs development and to minimize the potential risks when developing formulations.

Diversity of Antimicrobial Peptides in Three Partially Sympatric Frog Species in Northeast Asia and Implications for Evolution.

Antimicrobial peptides (AMPs) are evolutionarily ancient molecules that play an essential role in innate immunity across taxa from invertebrates to vertebrates. The evolution system of AMP system has not been well explained in the literature. In this study, we cloned and sequenced AMP transcriptomes of three frog species, namely Rana dybowskii, Rana amurensis, and Pelophylax nigromaculatus, which are partially sympatric in northeast Asia, but show different habitat preferences. We found that each species contained 7 to 14 families of AMPs and the diversity was higher in species with a large geographic range and greater habitat variation. All AMPs are phylogenetically related but not associated with the speciation process. Most AMP genes were under negative selection. We propose that the diversification and addition of novel functions and improvement of antimicrobial efficiency are facilitated by the expansion of family members and numbers. We also documented significant negative correlation of net charges and numbers of amino acid residues between the propiece and mature peptide segments. This supports the Net Charge Balance Hypothesis. We propose the Cut Point Sliding Hypothesis as a novel diversification mechanism to explain the correlation in lengths of the two segments.

CNS infections in patients with temporary CSF shunts: Diagnostic, preventive and therapeutic approach / Infecciones del SNC en pacientes con drenaje ventricular externo: aproximación diagnóstica, preventiva y terapéutica

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Pseudomonas aeruginosa nosocomial meningitis in neurosurgical patients with intraventricular catheters: Therapeutic approach and review of the literature / Meningitis nosocomial por Pseudomonas aeruginosa en pacientes portadores de catéteres intraventriculares: aproximación terapéutica y revisión de la literatura

BACKGROUND: Pseudomonas aeruginosa neurosurgical meningitis is a rare entity, usually related with intraventricular catheters and associated with high mortality rates. We describe the clinical characteristics, treatment and outcomes of a series of neurosurgical meningitis caused by P. aeruginosa along 1990-2016. METHODS: Descriptive, retrospective study of all postsurgical meningitis due to P. aeruginosa related to intraventricular catheters in Hospital Universitario Central de Asturias, between 1990 and 2016. Clinical features, therapeutic approaches and prognostic factors were analyzed statistically. A binary logistic regression analysis was performed to determine the factors influencing the infection mortality. RESULT: 51 episodes from 51 different patients with CSF culture positive for P. aeruginosa were reviewed. Seventeen patients (33.3%) died as a direct consequence of the infection. Univariate analysis showed that mortality was higher in the group of patients treated with ceftazidime (12 vs. 15, p = 0.068, OR 3.040 [0.877-10.544]) and lower in patients whom had received intrathecal therapy (2 vs. 13, p = 0.050, OR 4.64 [0.80-34.93]), without differences observed between those patients treated with aminoglycosides or with colistin. Any patient treated with colistin died (0 vs. 6, p = 0.067, OR: not defined). In the multivariate analysis mortality was only significant higher for patients without catheter withdrawal (p = 0.014) and lower for those patients who received intrathecal therapy (p = 0.05) or adequate empirical treatment (p = 0.006). CONCLUSIONS: The mortality of P. aeruginosa meningitis is high especially in infections without catheter withdrawal and in patients for whom the intrathecal route of administration was not used. Catheter withdrawal was an independent factor of good outcome in our series

ANTECEDENTES: La meningitis nosocomial por Pseudomonas aeruginosa es una entidad poco frecuente, generalmente relacionada con catéteres intraventriculares y asociada con altas tasas de mortalidad. Se describen las características clínicas, con especial hincapié en su tratamiento, de una serie de meningitis neuroquirúrgicas por P. aeruginosa entre 1990 y 2016. MÉTODOS: Estudio descriptivo, retrospectivo, de todas las meningitis posquirúrgicas por P. aeruginosa relacionadas con catéteres intraventriculares en el Hospital Universitario Central de Asturias entre 1990 y 2016, con especial hincapié en los enfoques terapéuticos y factores pronósticos. Los factores asociados con mortalidad se analizaron mediante regresión logística binaria. RESULTADOS: Se revisaron 51 episodios de 51 pacientes diferentes con cultivos de LCR positivos para P. aeruginosa. Diecisiete pacientes (33,3%) murieron como consecuencia directa de la infección. La mortalidad fue mayor en el grupo de pacientes tratados con ceftazidima (12 vs. 15, p = 0,068, OR 3,040 [0,877-10,544]) y menor en los pacientes que habían recibido terapia intratecal (2 vs. 13, p = 0,050, OR 4,64 [0,80-34,93]), sin diferencias en estos últimos entre los tratados con aminoglucósidos o con colistina. Ningún paciente tratado con colistina falleció (0 vs. 6, p = 0,067, OR no definida). El análisis multivariable únicamente confirmó la asociación con la ausencia de terapia intratecal (p = 0,05) o tratamiento empírico adecuado (p = 0,006). CONCLUSIONES: La mortalidad de la meningitis por P. aeruginosa es elevada, especialmente en pacientes en quienes no se utilizó la vía de administración intratecal. La retirada del catéter fue un factor independiente de buena evolución en nuestra serie