Incorporation of a Theranostic "Two-Tone" Luminescent Silver Complex into Biocompatible Agar Hydrogel Composite for the Eradication of ESKAPE Pathogens in a Skin and Soft Tissue Infection Model.

Microbial invasion and colonization of the skin and underlying soft tissues are among the most common types of infections, becoming increasingly prevalent in hospital settings. Systemic antibiotic chemotherapies are now extremely limited due to emergence of drug-resistant Gram-positive and multidrug-resistant Gram-negative bacterial strains. Topical administration of antimicrobials provides an effective route for the treatment of skin and soft tissue infections (SSTIs). Therefore, the development of new and effective materials for the delivery of these agents is of paramount importance. Silver is a broad-spectrum antibiotic used for the treatment and prevention of infections since ancient times. However, the high reactivity of silver cation (Ag+) makes its incorporation into delivery materials quite challenging. Herein we report a novel soft agar hydrogel composite for the delivery of Ag+ into infected wound sites. This material incorporates a Ag(I) complex [Ag2(DSX)2(NO3)2] (1; DSX = 5-(dimethylamino)- N, N-bis(pyridin-2-ylmethyl) naphthalene-1-sulfonamide) that exhibits a change in fluorescence upon Ag+ release and qualitatively indicates the end point of silver delivery. The antibacterial efficacy of the material was tested against several bacterial strains in an SSTI model. The complex 1-agar composite proved effective at eradicating the pathogens responsible for the majority of SSTIs. The theranostic (therapeutic/diagnostic) properties coupled with its stability, softness, ease of application, and removal make this material an attractive silver-delivery vehicle for the treatment and prevention of SSTIs.

[Uncommon non-fermenting Gram-negative rods as pathogens of lower respiratory tract infection]. / Ritkábban eloforduló, alsó légúti fertozést okozó Gram-negatív nem fermentáló pálcák.

INTRODUCTION: Glucose non-fermenting Gram-negative bacteria are ubiquitous environmental organisms. Most of them are identified as opportunistic, nosocomial pathogens in patients. Uncommon species are identified accurately, mainly due to the introduction of matrix-assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS) in clinical microbiology practice. Most of these uncommon non-fermenting rods are isolated from lower respiratory tract samples. Their significance in lower respiratory tract infections, such as rules of their testing are not clarified yet. AIM: The aim of this study was to review the clinical microbiological features of these bacteria, especially their roles in lower respiratory tract infections and antibiotic treatment options. METHOD: Lower respiratory tract samples of 3589 patients collected in a four-year period (2013-2016) were analyzed retrospectively at Semmelweis University (Budapest, Hungary). Identification of bacteria was performed by MALDI-TOF MS, the antibiotic susceptibility was tested by disk diffusion method. RESULTS: Stenotrophomonas maltophilia was revealed to be the second, whereas Acinetobacter baumannii the third most common non-fermenting rod in lower respiratory tract samples, behind the most common Pseudomonas aeruginosa. The total number of uncommon non-fermenting Gram-negative isolates was 742. Twenty-three percent of isolates were Achromobacter xylosoxidans. Beside Chryseobacterium, Rhizobium, Delftia, Elizabethkingia, Ralstonia and Ochrobactrum species, and few other uncommon species were identified among our isolates. The accurate identification of this species is obligatory, while most of them show intrinsic resistance to aminoglycosides. Resistance to ceftazidime, cefepime, piperacillin-tazobactam and carbapenems was frequently observed also. CONCLUSIONS: Ciprofloxacin, levofloxacin and trimethoprim-sulfamethoxazole were found to be the most effective antibiotic agents. Orv Hetil. 2018; 159(1): 23-30.

Non-fermentative Gram-negative rods bacteremia in children with cancer: a 14-year single-center experience.

PURPOSE: Data on non-fermentative Gram-negative rods (NFGNR) bacteremia in children with malignancies are limited. The aim of this study was to present clinical picture, antimicrobial susceptibility pattern, risk factors for resistance and outcome in NFGNR bacteremia in children with cancer. METHODS: All episodes of NFGNR bacteremia occurring during 2001-2014 in children with cancer in a tertiary-care hospital were retrospectively analyzed. Pseudomonas and Acinetobacter spp. resistant to three or more antibiotic classes and all Stenotrophomonas maltophilia (SM) were defined as multidrug-resistant bacteria (MDR). RESULTS: A total of 80 children (44 males, 0.8-18 years, median 5 years) developed 107 episodes (116 pathogens) of NFGNR bacteremia; Pseudomonas aeruginosa (PA) (51; 43.9%), Acinetobacter baumannii (AB) (21, 18.1%), SM (18, 15.5%); and others (27, 25.2%). The rate of NFGNR bacteremia in children with certain solid tumors (e.g. sarcoma, 12/134 (9.0%)) was comparable to that of hematological malignancies (52/429 (12.2%). Focal infection and septic shock occurred in 16 (14.9%) and four (3.7%) episodes, respectively. Thirty (25.8%) of 116 NFGNR were MDR. The most significant predictors of bacteremia with MDR PA or AB were severe neutropenia (<100 cells/mm3; OR 7.8, p = 0.002), hospital-acquired (OR 16.9, p < 0.0001) and breakthrough (OR 11.2, p < 0.0001) infection. Infection with MDR bacteria was associated with inappropriate empirical therapy. The 30-day mortality was 3/107 (2.8%), all in neutropenic patients with hematological malignancies. CONCLUSIONS: NFGNR bacteremia can present with nonspecific signs or symptoms. MDR NFGNRs are common and compromise treatment options, but mortality is relatively low. Knowledge of local epidemiology, pattern and risk factors for resistance is important to guide empirical therapy.

Intrathecal/intraventricular colistin in external ventricular device-related infections by multi-drug resistant Gram negative bacteria: case reports and review.

We report three cases of external ventricular derivation infections caused by multidrug-resistant Gram-negative rods and treated successfully with intraventricular colistin. The intrathecal or intraventricular use of colistin have been reported in more than 100 cases without any consensus on dosage, duration and type (monotherapy or combination therapy) of treatment. Based on our comprehensive review of the relevant literature relating to both clinical and pharmacokinetic data, we conclude that the intrathecal/intraventricular administration of colistin is a safe and effective option to treat central nervous system infections caused by multidrug-resistant Gram-negative bacteria.

Carbapenem disks on MacConkey agar in screening methods for detection of carbapenem-resistant Gram-negative rods in stools.

Direct plating of simulated stool specimens on MacConkey agar (MCA) with 10-µg ertapenem, meropenem, and imipenem disks allowed the establishment of optimal zone diameters for the screening of carbapenem-resistant Gram-negative rods (CRGNR) of ≤ 24 mm (ertapenem), ≤ 34 mm (meropenem), and ≤ 32 mm (imipenem).

Effect of HMG-CoA reductase inhibitors on antimicrobial susceptibilities for gram-negative rods.

Epidemiologic evidence suggests a beneficial effect of HMG-CoA reductase inhibitors (statins) in sepsis, and in-vitro data exist for antimicrobial activity of statins against some bacteria and fungi. We examined whether statin exposure at physiologic concentrations enhances activity of selected antimicrobials against Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. Broth microdilution was performed with and without dose-ranging concentrations of lovastatin, fluvastatin, atorvastatin, pravastatin and simvastatin. No effects on antimicrobial activity were demonstrated.

Antibacterial activity of extracts from five medicinal plants and their formula against bacteria that cause chronic wound infection.

BACKGROUND: Chronic wound is caused by various factors such as chemotherapy, gene damage, treatment with steroids, diabetes mellitus, renal failure, blood pressure, infection and nutritional factors. One of the most common causes is bacterial infection. Antibacterial activity of several herbal plants has been reported. Thai medicinal plants which possess biological activities are potential to develop an alternative treatment of bacterial infection. OBJECTIVE: To study efficiency of extracts from medicinal plants and their formula against bacteria that cause chronic wound infection. MATERIAL AND METHOD: Extraction of Thai medicinal plants including Curcuma longa Linn, Rhinacanthus nasutus Linn, Garcinia mangostana Linn, Caesalpinia sappan Linn and Centellia asiatica Linn was performed by maceration with 95% ethanol and decoction followed by freeze dry. Formulation was conducted by varying the ratio of each components. Antibacterial activity were determined disk diffusion and broth dilution against Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Acinetobacter baumanii, Escherichia coli and Klebsiella pneumoniae. RESULTS: Ethanolic extracts exhibited better antibacterial activity against tested strains than water extracts. Antibacterial activity of Caesalpinia sappan Linn. against S. aureus and MRSA showed the most effective with MIC value of 0.625 mg/ml. One of the five different formulas which contained two times proportion of C. sappan revealed that this formula was able to inhibit all tested strains with the MIC ranging between 0.156 mg/ml and 10 mg/ml. CONCLUSION: C. sappan is the most effective herbal plant. The formula with two times proportion of C. sappan is potentially best formula for development of medicinal product of chronic wound infection. The potential active compound of C. sappan is suggested for further investigation of antimicrobial activity and other biological properties.

Antimicrobial-resistant pathogens associated with adult healthcare-associated infections: Summary of data reported to the National Healthcare Safety Network, 2015-2017.

OBJECTIVE: Describe common pathogens and antimicrobial resistance patterns for healthcare-associated infections (HAIs) that occurred during 2015-2017 and were reported to the Centers for Disease Control and Prevention's (CDC's) National Healthcare Safety Network (NHSN). METHODS: Data from central line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), ventilator-associated events (VAEs), and surgical site infections (SSIs) were reported from acute-care hospitals, long-term acute-care hospitals, and inpatient rehabilitation facilities. This analysis included device-associated HAIs reported from adult location types, and SSIs among patients ≥18 years old. Percentages of pathogens with nonsusceptibility (%NS) to selected antimicrobials were calculated for each HAI type, location type, surgical category, and surgical wound closure technique. RESULTS: Overall, 5,626 facilities performed adult HAI surveillance during this period, most of which were general acute-care hospitals with <200 beds. Escherichia coli (18%), Staphylococcus aureus (12%), and Klebsiella spp (9%) were the 3 most frequently reported pathogens. Pathogens varied by HAI and location type, with oncology units having a distinct pathogen distribution compared to other settings. The %NS for most pathogens was significantly higher among device-associated HAIs than SSIs. In addition, pathogens from long-term acute-care hospitals had a significantly higher %NS than those from general hospital wards. CONCLUSIONS: This report provides an updated national summary of pathogen distributions and antimicrobial resistance among select HAIs and pathogens, stratified by several factors. These data underscore the importance of tracking antimicrobial resistance, particularly in vulnerable populations such as long-term acute-care hospitals and intensive care units.

Genes involved in arsenic transformation and resistance associated with different levels of arsenic-contaminated soils.

BACKGROUND: Arsenic is known as a toxic metalloid, which primarily exists in inorganic form [As(III) and As(V)] and can be transformed by microbial redox processes in the natural environment. As(III) is much more toxic and mobile than As(V), hence microbial arsenic redox transformation has a major impact on arsenic toxicity and mobility which can greatly influence the human health. Our main purpose was to investigate the distribution and diversity of microbial arsenite-resistant species in three different arsenic-contaminated soils, and further study the As(III) resistance levels and related functional genes of these species. RESULTS: A total of 58 arsenite-resistant bacteria were identified from soils with three different arsenic-contaminated levels. Highly arsenite-resistant bacteria (MIC > 20 mM) were only isolated from the highly arsenic-contaminated site and belonged to Acinetobacter, Agrobacterium, Arthrobacter, Comamonas, Rhodococcus, Stenotrophomonas and Pseudomonas. Five arsenite-oxidizing bacteria that belonged to Achromobacter, Agrobacterium and Pseudomonas were identified and displayed a higher average arsenite resistance level than the non-arsenite oxidizers. 5 aoxB genes encoding arsenite oxidase and 51 arsenite transporter genes [18 arsB, 12 ACR3(1) and 21 ACR3(2)] were successfully amplified from these strains using PCR with degenerate primers. The aoxB genes were specific for the arsenite-oxidizing bacteria. Strains containing both an arsenite oxidase gene (aoxB) and an arsenite transporter gene (ACR3 or arsB) displayed a higher average arsenite resistance level than those possessing an arsenite transporter gene only. Horizontal transfer of ACR3(2) and arsB appeared to have occurred in strains that were primarily isolated from the highly arsenic-contaminated soil. CONCLUSION: Soils with long-term arsenic contamination may result in the evolution of highly diverse arsenite-resistant bacteria and such diversity was probably caused in part by horizontal gene transfer events. Bacteria capable of both arsenite oxidation and arsenite efflux mechanisms had an elevated arsenite resistance level.

[Comparison between agar dilution and three other methods for determining the susceptibility of 228 clinical isolates of non-fermenting gram-negative rods]. / Comparación entre dilución en agar y otras 3 técnicas para la determinación de la sensibilidad de 228 aislamientos clínicos de bacilos gramnegativos no fermentadores.

INTRODUCTION: Susceptibility testing for non-fermenting gram-negative rods (NFGNR) is problematic; valid methods are needed for this purpose. METHODS: In this study, 228 NFGNR clinical isolates were evaluated, including 85 Acinetobacter spp., 80 Stenotrophomonas maltophilia, 50 Pseudomonas aeruginosa, and 13 other species (8 Ralstonia pickettii and 5 Burkholderia cepacia). Agar dilution was used as the reference method, and results were compared with those obtained by disk diffusion, Etest, and microdilution performed with the VITEK 2 Compact System. RESULTS: The disk method was unacceptable for S. maltophilia and P. aeruginosa, in the latter organism, mainly because of poor agreement in the colistin results. Nonetheless, the disk method is valid for Acinetobacter spp. and the remaining NFGNRs. The VITEK 2 Compact System yielded poor results for piperacillin-tazobactam, tigecycline, and ceftazidime in S. maltophilia. There were minor discrepancies with the VITEK 2 Compact system and the Etest for tigecycline in Acineobacter spp. and S. maltophilia, likely because of the differing composition of the Muller-Hinton agar lots. Hence, Etest results should be interpreted with caution. CONCLUSION: The disk diffusion method is inadequated for S. maltophilia. This method is unacceptable for testing colistin in P. aeruginosa. The methods Vitek 2 Compact System and Etest show minor discrepancies for testing S. maltophilia and Acinetobacter spp. for tigecycline.

Effect of xylitol on an in vitro model of oral biofilm.

PURPOSE: The aim of the present study was to examine whether xylitol, at different concentrations, inhibits the formation of an experimental model of oral biofilm. MATERIALS AND METHODS: Biofilms of six bacterial species (Streptococcus mutans, Streptococcus sobrinus, Lactobacillus rhamnosus, Actinomyces viscosus, Porphyromonas gingivalis and Fusobacterium nucleatum) were prepared on hydroxyapatite (HA) discs according to the Zürich Biofilm Model. Xylitol was tested at two concentrations, 1% and 3%. At the end of their designated incubation times, some HA discs were destined for confocal laser scanning microscopy (CLSM) and the others were harvested using a sterile surgical instrument. Aliquots of harvested biofilms were diluted and plated onto specific media. After a 48-h anaerobic incubation at 37 degrees C, the colony-forming units (CFUs) were counted. RESULTS: CLSM images showed that only a small amount of isolated bacteria was observed on the surface of HA discs. Culture of harvested biofilms showed an inhibition in the growth of different species included in the biofilms. CONCLUSIONS: Xylitol has a clear inhibitory effect on the formation of the experimental biofilms. This study shows that xylitol is not only efficient in inhibiting the acid production of cariogenic bacteria, but also in preventing the formation of a multispecies biofilm; it confirms the relevance of the use of this polyol for the prevention of oral diseases caused by dental plaque.

[Monitoring of antibiotic resistance of gram negative anaerobes]. / Surveillance de la résistance aux antibiotiques des anaérobies stricts à Gram négatif.

MATERIAL AND METHOD: Using an agar reference method (Norma M11-A5, National Committee for Clinical and Laboratory Standards) the minimal inhibitory concentrations of nine antibiotics were determined for 376 anaerobic strains. The following strains were investigated: 254 Bacteroides fragilis group (including 143 B. fragilis), 122 other gram-negative anaerobes (Bacteroides spp., Prevotella, Fusobacterium, Porphyromonas, Suterella, Desulfomonas, Veillonella). RESULTS: In the B. fragilis group resistance rates were: coamoxyclav 2.8%, ticarcillin 27.5%, ticarcillin-clavulanic acid 1.9%, piperacillin-tazobactam 1.9%, cefoxitin 6.2%, imipenem 0.8%, clindamycin 28.3%, respectively. Based on previous studies, resistance to imipenem remained low in 2003 and was only observed for B. fragilis. Resistance to clindamycin was maintained around 25%. No metronidazole resistance was observed, but decreased susceptibility was found for B. fragilis, B. merdae and Prevotella, as in 4.3% of gram-negative anaerobes. DISCUSSION: This study confirms the high resistance rate of gram-negative anaerobes to clindamycin, the efficient activity of imipenem, beta-lactam/beta-lactamase inhibitor combinations and metronidazole. However, reduced metronidazole susceptibility seems to be increasing.

[Assessment of the susceptibility of the gram-negative rods isolated from hospitalized patients to cefoperazone/sulbactam]. / Ocena wrazliwosci na cefoperazon/sulbaktam szczepów paleczek gram-ujemnych izolowanych od chorych hospitalizowanych.

The susceptibility to cefoperazone/sulbactam of 197 strains of Gram-negative rods demonstrating an ESBL-positive phenotype was determined. The assortment of the investigated strains was as follows (numbers of strains are given in the brackets): E. cloacae (63), S. marcescens (46), K. pneumoniae (21), P. mirabilis (17), E. coli (9), P. vulgaris (8), P. aeruginosa (20) and A. baumanni (13). 83 strains from 197 were susceptible (42.1%). The MIC values were determined and the disc-diffusion method was performed. The susceptibilities among particular species were as follows (the order of data in the brackets is: % of the susceptible strains/MIC50/MIC90): E. cloacae (54.0/16/64), S. marcescens (23.9/64/> or = 128), K. pneumoniae (38.1/32/64), P. mirabilis (41.2/32/64), E. coli (44.4/32/32), P. vulgaris (75.0/8/32), P. aeruginosa (35.0/32/64), A. baumannii (46.2/32/64). Using disc-diffusion method, for 184 strains the difference between diameter of the inhibition zone around the disc with cefoperazone and the disc with cefoperazone/sulbactam was calculated. This difference amounted 5 mm or more in the case of 76.6% of the investigated strains. The results indicate that the comparison of the inhibition zones around cefoperazone and cefoperazone/sulbactam discs may be an additional method useful for phenotypic detection of ESBL producing organisms. These results highly correlated with results obtained by using analogous test with cefpirome and cefpirome/clavulanic acid (85.6% of concordance).

In vitro antibacterial activities of tigecycline and comparative agents by time-kill kinetic studies in fresh Mueller-Hinton broth.

Time-kill kinetics performed with tigecycline, in fresh MHB, demonstrated a consistent 1 to 2 log(10) CFU/ml reduction in bacterial counts against the majority of clinically relevant pathogens tested. Although classified as a bacteriostatic agent, tigecycline shows bactericidal activity against select isolates associated with serious infection. In general, vancomycin and imipenem demonstrated bactericidal activity.

Reevaluation of current susceptibility breakpoints for Gram-negative rods based on pharmacodynamic assessment.

Although pharmacodynamic (PD) modeling is now being considered for decision support for susceptibility breakpoint determination against Gram-negative bacteria, these PD-derived breakpoints should be verified using a clinically applicable population of organisms. In this analysis, a 5000-patient Monte Carlo simulation was used to determine PD breakpoints, the highest 2-fold MIC in which the probability of bactericidal target attainment (PTA) remained > or = 90%. Percent susceptibilities for 639 Pseudomonas aeruginosa, 103 Acinetobacter baumannii, 705 Escherichia coli, and 418 Klebsiella spp. collected during the 2004 Meropenem Yearly Susceptibility Test Information Collection surveillance study were then defined according to the PD-derived breakpoint (%S(PD)) and compared with the current Clinical Laboratory Standards Institute (CLSI)-defined breakpoints (%S(CLSI)). %S(PD) and %S(CLSI) were compared with the bactericidal PTA for each pathogen population to determine the degree of agreement. Resulting PD breakpoints were drug and dose dependent; moreover, values were commonly 2 to 4 MIC dilutions lower than CLSI breakpoints. Overall, %S(PD) more closely agreed with the PTA for the tested beta-lactam and fluoroquinolone dosing regimens. In contrast, %S(CLSI) overestimated PTA for many dosing regimens, especially against Pseudomonas: piperacillin/tazobactam 4.5 g qid (+9.7%), ciprofloxacin 0.4 g bid (+13.7%) and 0.4 g tid (+9.3%), and levofloxacin 0.5 g every 24 h (+22.4%) and 0.75 g every 24 h (+9.9%). Differences were most pronounced against the nonfermenting Gram-negative bacteria and were not observed among the Enterobacteriaceae. As a result, a new method of breakpoint classification is proposed, which is dosing regimen and pathogen specific, and is designed to denote isolates as susceptible only if target bactericidal exposures are achievable with the dosing regimen selected.

Comparison of Etest, Vitek and agar dilution for susceptibility testing of colistin.

In total, 172 isolates of Enterobacteriaceae, Acinetobacter spp., Pseudomonas aeruginosa and Stenotrophomonas maltophilia were tested for susceptibility to colistin by agar dilution, Etest and the Vitek 2 system. Isolates with a colistin MIC < or =2 mg/L were considered to be susceptible. Fifty-four (31%) Gram-negative isolates were resistant to colistin. Categorical agreement between agar dilution and Etest was 87%, and between agar dilution and Vitek 2 was 82%. Based on the data obtained, the Vitek 2 system was unreliable for detecting colistin resistance, and results obtained by Etest may require confirmation by a standard MIC susceptibility testing method.

Antibiotic regimens and intestinal colonization with antibiotic-resistant gram-negative bacilli.

The intestinal tract provides an important reservoir for antibiotic-resistant gram-negative bacilli, including Enterobacteriaceae species, Pseudomonas aeruginosa, and Acinetobacter baumannii. Selective pressure exerted by antibiotics plays a crucial role in the emergence and dissemination of these pathogens. Many classes of antibiotics may promote intestinal colonization by health care-associated gram-negative bacilli, because the organisms are often multidrug resistant. Antibiotics may inhibit colonization by gram-negative pathogens that remain susceptible, but the benefits of this effect are often limited because of the emergence of resistance. Antibiotic formulary alterations and standard infection control measures have been effective in controlling outbreaks of colonization and infection with antibiotic-resistant gram-negative pathogens. Additional research is needed to clarify the role of strategies such as selective decontamination of the digestive tract and decontamination of environmental surfaces and of patients' skin and wounds.

Resistance in nonfermenting gram-negative bacteria: multidrug resistance to the maximum.

Nonfermenting gram-negative bacteria pose a particular difficulty for the healthcare community because they represent the problem of multidrug resistance to the maximum. Important members of the group in the United States include Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, and Burkholderia cepacia. These organisms are niche pathogens that primarily cause opportunistic healthcare-associated infections in patients who are critically ill or immunocompromised. Multidrug resistance is common and increasing among gram-negative nonfermenters, and a number of strains have now been identified that exhibit resistance to essentially all commonly used antibiotics, including antipseudomonal penicillins and cephalosporins, aminoglycosides, tetracyclines, fluoroquinolones, trimethoprim-sulfamethoxazole, and carbapenems. Polymyxins are the remaining antibiotic drug class with fairly consistent activity against multidrug-resistant strains of P aeruginosa, Acinetobacter spp, and S maltophilia. However, most multidrug-resistant B cepacia are not susceptible to polymyxins, and systemic polymyxins carry the risk of nephrotoxicity for all patients treated with these agents, the elderly in particular. A variety of resistance mechanisms have been identified in P aeruginosa and other gram-negative nonfermenters, including enzyme production, overexpression of efflux pumps, porin deficiencies, and target-site alterations. Multiple resistance genes frequently coexist in the same organism. Multidrug resistance in gram-negative nonfermenters makes treatment of infections caused by these pathogens both difficult and expensive. Improved methods for susceptibility testing are needed when dealing with these organisms, including emerging strains expressing metallo-beta-lactamases. Improved antibiotic stewardship and infection-control measures will be needed to prevent or slow the emergence and spread of multidrug-resistant, nonfermenting gram-negative bacilli in the healthcare setting.

Potentially multidrug-resistant non-fermentative Gram-negative pathogens causing nosocomial pneumonia.

Owing to its high morbidity and mortality, nosocomial pneumonia represents a particularly serious illness and one of the most frequent complications in ventilated patients admitted to the Intensive Care Unit. Gram-negative microorganisms, such as Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia, are the most relevant pathogens responsible for particularly difficult-to-treat nosocomial pneumonia. The intrinsic resistance of these bacteria to many antimicrobial agents and, in addition, the variety of their increasingly recognised acquired resistance mechanisms make their management in the hospital setting problematic. Antimicrobials that retain the best activity against P. aeruginosa include carbapenems, piperacillin, cefepime, ceftazidime, ciprofloxacin and certain aminoglycosides, whilst carbapenems and sulphamethoxazole/trimethoprim remain the most active agents against A. baumannii and S. maltophilia, respectively. However, the growing emergence among these microorganisms of multidrug-resistant (MDR) isolates and the severity of associated infections call for potential alternative drugs. Sulbactam alone or in combination with ampicillin may represent an acceptable option for MDR A. baumannii as well as colistin, which also covers MDR P. aeruginosa. Newer fluoroquinolones and some tetracyclines may be alternative drugs both for MDR S. maltophilia and A. baumannii. However, large-scale controlled clinical trials are needed to confirm these promising therapeutic options.