Resistant Stenotrophomonas Maltophilia Research Articles

In vitro Antimicrobial Activity and Dose Optimization of Eravacycline and Other Tetracycline Derivatives Against Levofloxacin-Non-Susceptible and/or Trimethoprim-Sulfamethoxazole-Resistant Stenotrophomonas maltophilia.

To better guide clinical use, we determined the in vitro antimicrobial activity of the new drug eravacycline and other tetracycline derivatives against levofloxacin (LVFX)-non-susceptible and/or trimethoprim-sulfamethoxazole (TMP-SMZ)-resistant Stenotrophomonas maltophilia and evaluated their dosing regimens. Seventy-seven unique strains of S. maltophilia were isolated from sputa samples and airway aspirate samples that were either LVFX-non-susceptible and/or TMP-SMZ-resistant. Monte Carlo simulations were performed for different dosing regimens according to the population pharmacokinetic parameters of antibiotics in patients with respiratory tract infections at the minimum inhibitory concentration (MIC). Eravacycline had excellent in vitro antibacterial activity against LVFX-non-susceptible and/or TMP-SMZ-resistant S. maltophilia. Monte Carlo simulations showed that for LVFX-non-susceptible strains, the cumulative fraction of response (CFR) of minocycline at the conventional recommended dose of 100 mg q12 h was 90.90%; for TMP-SMZ-resistant strains, the CFR of minocycline at a high dose of 200 mg q12 h was only 91.64%. For strains resistant to both LVFX and TMP-SMZ, the CFR of minocycline at a high dose of 200 mg q12 h was 89.81%. In contrast, the CFR of tigecycline was less than 40%, even at a dose of 100 mg q12 h. For pneumonia, minocycline is better for S. maltophilia that is non-susceptible to LVFX; for TMP-SMZ-resistant strains and strains that are not susceptible to either LVFX or TMP-SMZ, the efficiency of eravacycline requires further evaluation. Eravacycline may be a better choice for extremely resistant S. maltophilia strains that are non-susceptible to LVFX, TMP-SMZ, and minocycline.

In Vitro Comparison of Aztreonam/Amoxicillin-Clavulanate Versus Aztreonam/Ceftazidime-Avibactam on Ceftazidime-Avibactam Resistant Stenotrophomonas maltophilia.

We investigated the in vitro susceptibility of ceftazidime-avibactam (CZA) resistant Stenotrophomonas maltophilia to the associations aztreonam/amoxicillin-clavulanate (ATM-AMC) and ATM-CZA. Forty clinical isolates of S. maltophilia recovered from sputum samples of 40 cystic fibrosis people were selected from the collection of the Nantes University Hospital, based on their resistance to CZA. Minimum inhibitory concentrations (MICs) of ATM-CZA and ATM-AMC were determined for each isolate by an Etest strip superposition method, and by Etest for each individual antibiotic. MICs of CZA, ATM, and AMC ranged from 12 to ≥256, ≥256, and 16 to ≥256 mg/L, respectively. Synergistic effects were observed with the ATM-CZA combination for all isolates (fractional inhibitory concentration index range of 0.01 to 0.27), with combination MICs ranging from 0.75 to 16 mg/L (MIC50/90 = 3/12 mg/L), corresponding to a decrease of at least 16-folds in the MIC of ATM. In 23 (57.5%) S. maltophilia isolates, the association of AMC to ATM was also synergistic and combination MICs were ≤16 mg/L (EUCAST breakpoint for ATM resistance in Pseudomonas aeruginosa). Our results show that ATM-CZA or ATM-AMC could be alternative therapeutic options against some highly resistant S. maltophilia. This encourages further experimental studies, in particular time-kill analyses, and clinical trials to delineate conditions required for use of these combinations in practice.

Characterisation of Bacteriophage vB_SmaM_Ps15 Infective to Stenotrophomonas maltophilia Clinical Ocular Isolates.

Recent acknowledgment that multidrug resistant Stenotrophomonas maltophilia strains can cause severe infections has led to increasing global interest in addressing its pathogenicity. While being primarily associated with hospital-acquired respiratory tract infections, this bacterial species is also relevant to ophthalmology, particularly to contact lens-related diseases. In the current study, the capacity of Stenotrophomonas phage vB_SmaM_Ps15 to infect ocular S. maltophilia strains was investigated to explore its future potential as a phage therapeutic. The phage proved to be lytic to a range of clinical isolates collected in Australia from eye swabs, contact lenses and contact lens cases that had previously shown to be resistant to several antibiotics and multipurpose contact lenses disinfectant solutions. Morphological analysis by transmission electron microscopy placed the phage into the Myoviridae family. Its genome size was 161,350 bp with a G + C content of 54.2%, containing 276 putative protein-encoding genes and 24 tRNAs. A detailed comparative genomic analysis positioned vB_SmaM_Ps15 as a new species of the Menderavirus genus, which currently contains six very similar globally distributed members. It was confirmed as a virulent phage, free of known lysogenic and pathogenicity determinants, which supports its potential use for the treatment of S. maltophilia eye infections.

Inter-species interactions alter antibiotic efficacy in bacterial communities

The efficacy of antibiotic treatments targeting polymicrobial communities is not well predicted by conventional in vitro susceptibility testing based on determining minimum inhibitory concentration (MIC) in monocultures. One reason for this is that inter-species interactions can alter the community members’ susceptibility to antibiotics. Here we quantify, and identify mechanisms for, community-modulated changes of efficacy for clinically relevant antibiotics against the pathogen Pseudomonas aeruginosa in model cystic fibrosis (CF) lung communities derived from clinical samples. We demonstrate that multi-drug resistant Stenotrophomonas maltophilia can provide high levels of antibiotic protection to otherwise sensitive P. aeruginosa. Exposure protection to imipenem was provided by chromosomally encoded metallo-β-lactamase that detoxified the environment; protection was dependent upon S. maltophilia cell density and was provided by S. maltophilia strains isolated from CF sputum, increasing the MIC of P. aeruginosa by up to 16-fold. In contrast, the presence of S. maltophilia provided no protection against meropenem, another routinely used carbapenem. Mathematical ordinary differential equation modelling shows that the level of exposure protection provided against different carbapenems can be explained by differences in antibiotic efficacy and inactivation rate. Together, these findings reveal that exploitation of pre-occurring antimicrobial resistance, and inter-specific competition, can have large impacts on pathogen antibiotic susceptibility, highlighting the importance of microbial ecology for designing successful antibiotic treatments for multispecies communities.

Immunoinformatics based designing and simulation of multi-epitope vaccine against multi-drug resistant Stenotrophomonas maltophilia

Stenotrophomonas maltophilia is a leading opportunistic bacterium responsible for a variety of nosocomial infections in humans, particularly among immunocompromised population. Therapeutic options are limited due to pathogen profound resistance and lack of a licensed vaccine. To address this problem, an integrative computational strategy including subtractive proteomics, immuno-informatics, molecular dynamics simulation, and immune response simulation is employed herein to design an efficacious multi-epitope vaccine against S. maltophilia. Four putative antigenic membrane proteins: Methyl-accepting chemotaxis, Putative outer-membrane usher, Fimbrial biogenesis outer-membrane usher, and Flagellin unveiled as potential vaccine targets through subtractive proteomics. These proteins are non-human homologous, virulent, and crucial for pathogen survival. Stringent immunoinformatics analysis revealed two non-allergenic B-cell derived T-cell epitopes from FimD, capable of eliciting both humoral and cellular immunity. Multi-epitope construct is designed by stitching preferred peptides with immunogenicity enhancer adjuvant and linkers. Vaccine construct meets the criteria of physiochemistry, immunogenicity, and non-allergenicity. Docked pose of construct-TLR4 complex validated and subjected to molecular dynamics simulations to explore its dynamic behaviour in an aqueous environment. Structural changes were observed in complex, while vaccine construct remained exposed to TLR4 receptor surface. Immune simulations predicted significant T and B-cells proliferation, induced macrophage activity, with increased production of INF-γ, and IL-2 in response to the antigen. All these analyses predicted that this designed vaccine could provoke host robust immune responses and could serve as a protective antigen against S. maltophilia.

Biochemical and genomic characterization of a novel bacteriophage BUCT555 lysing Stenotrophomonas maltophilia

Stenotrophomonas maltophilia is a common conditional pathogen, and it is naturally resistant to most commonly used clinical antibiotics. The bacteriophage is considered to be a potential antibiotic alternative for treating multi-drug-resistant bacteria. In this study, a bacteriophage BUCT555 was isolated from hospital sewage for lysing the clinical multi-drug resistant Stenotrophomonas maltophilia. Electron microscopy studies revealed this phage belongs to the Podoviridae family. The double-stranded DNA genome of bacteriophage BUCT555 is composed of 39,440 bp with a GC content of 61.43%. The genome contains 57 open reading frames, 14 of which had assigned functions, while no virulence related genes, antibiotic resistance genes or tRNA were identified. The burst size of BUCT555 was 204 pfu per infected cell. Structure proteins of bacteriophage BUCT555 generated by SDS-PAGE and HPLC-MS revealed that it contains seven proteins with molecular weight ranging from 19 to 89 kDa. BLASTn analysis showed that phage BUCT555 has 2% homology with other phages in NCBI database, suggesting BUCT555 is a new phage genus of Podoviridae that infects Stenotrophomonas maltophilia. Characterization of the bacteriophage BUCT555 enriches our knowledge about the diversity of Stenotrophomonas maltophilia bacteriophages.

Emergence of concurrent levofloxacin- and trimethoprim/sulfamethoxazole-resistant Stenotrophomonas maltophilia: Risk factors and antimicrobial sensitivity pattern analysis from a single medical center in Taiwan.

The emergence of concurrent levofloxacin- and trimethoprim/sulfamethoxazole (TMP/SMX)-resistant Stenotrophomonas maltophilia (LTSRSM) in Taiwan is becoming a serious problem, but clinical data analysis on this has not been reported. A matched case-control-control study was conducted to investigate risk factors for LTSRSM occurrence in hospitalized patients. For patients with LTSRSM infection/colonization (the case group), two matched control groups were used: control group A with levofloxacin- and TMP/SMX-susceptible S. maltophilia (LTSSSM) and control group B without S. maltophilia. Besides, tigecycline, ceftazidime, cefepime, ciprofloxacin, gentamicin, amikacin, and colistin susceptibilities in collected LTSRSM and levofloxacin- and TMP/SMX-susceptible S. maltophilia (LTSSSM) isolates were compared. From January 2014 to June 2016, 129 LTSRSM from cultured 1213 S. maltophilia isolates (10.6%) were identified. A total of 107 LTSRSM infected patients paired with 107 LTSSSM-, and 107 non-S. maltophilia-infected ones were included. When compared with control group A, previous fluoroquinolone and TMP/SMX use was found to be independently associated with LTSRSM occurrence. When compared with control group B, mechanical ventilation, cerebrovascular disease, and previous fluoroquinolone use were risk factors for LTSRSM occurrence. Eighty-five LTSRSM and 85 LTSSSM isolates were compared for antibiotic susceptibilities; the resistance rates and minimum inhibitory concentrations of tigecycline and ceftazidime were significantly higher for LTSRSM than for LTSSSM isolates. The emergence of LTSRSM showing cross resistance to tigecycline and ceftazidime would further limit current therapeutic options. Cautious fluoroquinolone and TMP/SMX use may be helpful to limit such high-level resistant strains of S. maltophilia occurrence.

Characterization of a New Mixture of Mono-Rhamnolipids Produced by Pseudomonas gessardii Isolated from Edmonson Point (Antarctica).

Rhamnolipids (RLs) are surface-active molecules mainly produced by Pseudomonas spp. Antarctica is one of the less explored places on Earth and bioprospecting for novel RL producer strains represents a promising strategy for the discovery of novel structures. In the present study, 34 cultivable bacteria isolated from Edmonson Point Lake, Ross Sea, Antarctica were subjected to preliminary screening for the biosurfactant activity. The positive strains were identified by 16S rRNA gene sequencing and the produced RLs were characterized by liquid chromatography coupled to high resolution mass spectrometry (LC-HRESIMS) and liquid chromatography coupled with tandem spectrometry (LC-MS/MS), resulting in a new mixture of 17 different RL congeners, with six previously undescribed RLs. We explored the influence of the carbon source on the RL composition using 12 different raw materials, such as monosaccharides, polysaccharides and petroleum industry derivatives, reporting for the first time the production of RLs using, as sole carbon source, anthracene and benzene. Moreover, we investigated the antimicrobial potential of the RL mixture, towards a panel of both Gram-positive and Gram-negative pathogens, reporting very interesting results towards Listeria monocytogenes with a minimum inhibitory concentration (MIC) value of 3.13 µg/mL. Finally, we report for the first time the antimicrobial activity of RLs towards three strains of the emerging multidrug resistant Stenotrophomonas maltophilia with MIC values of 12.5 µg/mL.

Cotrimoxasole-Resistant Stenotropomonas maltophilia Infection : Case Report

Stenotrophomonas maltophilia is an important multidrug-resistant nosocomial pathogen associated with high mortality. This infection did not elucide clearly in Riau. We reported two Cotrimoxaxole Resistant Stenotrophomonas maltophilia in patient of Arifin Achmad Hospital which refered from peripheral hospital in another region. They had similar clinical appereance such as long stay hospitalization, bad clinical appearance and had a history of meropenem exposure before. We performed urin culture to make appropriate diagnostic and treatment also. Stenotrophomonas maltophilia bacteria was found in urine isolate. The sensitivity test showed that this bacteria had Cotrimoxasole resistant that standard antibiotic of this bacteria. The management of these cases become complicated due to decrease of renal function in one patient. We had to make dose adjustment of parenteral levofloxacin, giving good nutrition, counted fluid balance and repaired others clinical conditions.Beside of its high mortality and morbidity, the outcomes of both these patients were good.

Transformation of Multi-Antibiotic Resistant Stenotrophomonas maltophilia with GFP Gene to Enable Tracking its Survival on Pine Trees

Pinus massoniana Lamb., commonly known as Masson Pine, is one of the most important tree species for planted forests in China. This species is, however, threatened by pine wilt disease caused by Bursaphelenchus xylophilus. Stenotrophomonas maltophilia (Palleroni & Bradbury 1993) Smal-007, a bacterium isolated from the body surface of native B. xylophilus, was evidenced to possess the ability to prevent and control this disease. In this study, we focus on exploring effective transformation and green fluorescent protein (GFP)-labeling of Smal-007, in order to facilitate its later investigation. The results indicated that the recombination of antibiotic Tp (trimethoprim), and the uncoupling reagent, CCCP (carbonyl cyanide m-chlorophenyl hydrazine), was effective for the transformation of the multidrug-resistant bacterium. An optimal transformation procedure, including electroporation, was established. To the best of our knowledge, this is the first report where such a method was used for S. maltophilia transformation. Furthermore, Smal-007 was labeled by GFP, allowing the monitoring of its survival ability in pine trees. The labeling was robust and recognizable in isolates recovered from pine needles and bark. In summary, our study indicated that combining uncoupling reagents could be a useful approach to finding operative antibiotic markers for the transformation of multidrug-resistant bacteria. In addition, our successful labeling of Smal-007 with GFP could improve the understanding of its ecological impact, when used as a biocontrol agent.

Structural/mechanistic insights into the efficacy of nonclassical β-lactamase inhibitors against extensively drug resistant Stenotrophomonas maltophilia clinical isolates.

Clavulanic acid and avibactam are clinically deployed serine β-lactamase inhibitors, important as a defence against antibacterial resistance. Bicyclic boronates are recently discovered inhibitors of serine and some metallo β-lactamases. Here, we show that avibactam and a bicyclic boronate inhibit L2 (serine β-lactamase) but not L1 (metallo β-lactamase) from the extensively drug resistant human pathogen Stenotrophomonas maltophilia. X-ray crystallography revealed that both inhibitors bind L2 by covalent attachment to the nucleophilic serine. Both inhibitors reverse ceftazidime resistance in S. maltophilia because, unlike clavulanic acid, they do not induce L1 production. Ceftazidime/inhibitor resistant mutants hyperproduce L1, but retain aztreonam/inhibitor susceptibility because aztreonam is not an L1 substrate. Importantly, avibactam, but not the bicyclic boronate is deactivated by L1 at a low rate; the utility of avibactam might be compromised by mutations that increase this deactivation rate. These data rationalize the observed clinical efficacy of ceftazidime/avibactam plus aztreonam as combination therapy for S. maltophilia infections and confirm that aztreonam-like β-lactams plus nonclassical β-lactamase inhibitors, particularly avibactam-like and bicyclic boronate compounds, have potential for treating infections caused by this most intractable of drug resistant pathogens.

Multidrug resistant Stenotrophomonas maltophilia: An emerging cause of hospital acquired infections in Assiut University Hospitals, Egypt

Stenotrophomonas maltophilia is an emergent pathogen in health¬care facilities worldwide that is intrinsically resistant to many antibiotics. We aimed to determine the prevalence of S. maltophila causing health care associated infections (HAIs) and environmental contamination at the intensive care units (ICUs) of Assiut University Hospitals, the antibiotic resistance profiles, production of metallo-β-lactamases (MBLs) and detection of sul 2 gene. A total of 690 clinical samples and 4151 environmental samples were collected. S. maltophila isolates were identified and confirmed by detection of 16S rRNA-23S rRNA gene by PCR. Antimicrobial resistance was determined by Kirbey Bauer disc diffusion method and imipenem MIC by E test. The presence of MBLs were detected by combined disc test (CDT) and double disc synergy test (DDST). The presence of sul 2 gene was determined by PCR. S. maltophila caused 9.7% of HAIs in the ICUs mostly respiratory tract infections and 0.67% of environmental contamination . A high percentage of resistance was found for most of the studied antimicrobials including carbapenems. MBLs were detected in all imipenem resistant isolates and in variable percentages in imipenem sensitive isolates. The least resistance found was to trimethoprim sulfamethoxazole (SXT). All SXT resistant isolates harboured the sul 2 gene. Multidrug resistance was reported in 63.5% of isolates. S. maltophilia causes a considerable percentage of HAIs especially respiratory tract infections and environmental contamination in the ICUs. A high percentage is MDR. Trimethoprim-sulfamethoxazole is the single agent of choice for the treatment of S. maltophilia infections. The detection of sul2 gene and MBLs among isolates at our hospitals is alarming.

Risk factors for hospital acquisition of trimethoprim-sulfamethoxazole resistant Stenotrophomonas maltophilia in adults: A matched case-control study.

The emergence of trimethoprim-sulfamethoxazole resistant Stenotrophomonas maltophilia (TSRSM) represents a serious threat to patients. The aim of current study was to identify risk factors associated with hospital-acquired TSRSM occurrence in adult inpatients. We conducted a matched case-control study in Tri-Service General Hospital, Taipei, Taiwan. From January 2014 through June 2015, case patients with TSRSM and control patients with trimethoprim-sulfamethoxazole susceptible S. maltophilia (TSSSM) during hospitalization were identified. Control patients were matched with TSRSM cases for age (within five years), sex, and site of isolation at a ratio of 1:1. A total of 266 patients were included in our study (133 cases and 133 matched controls). Bivariable analysis showed that previous exposure to fluoroquinolone [odds ratio (OR), 2.693; 95% confidence interval (CI, 1.492-5.884; p=0.002)], length of intensive care unit stay (OR, 1.015 per day; 95% CI, 1.001-1.030; p=0.041), and length of hospital stay (OR, 1.012 per day; 95% CI, 1.002-1.023; p=0.018) prior to S. maltophilia isolation were associated with TSRSM occurrence. A multivariable analysis showed that previous exposure to fluoroquinolone (OR, 3.158; 95% CI, 1.551-6.430; p=0.002) was an independent risk factor for TSRSM occurrence after adjustment. Previous fluoroquinolone use was an independent risk factor for hospital-acquired TSRSM occurrence in adult inpatients, suggesting that judicious administration of fluoroquinolone may be important for limiting TSRSM occurrence.

Antibiotic susceptibility of sulfamethoxazole-trimethoprim resistant Stenotrophomonas maltophilia strains isolated at a tertiary care centre in Hungary.

Sulfamethoxazole-trimethoprim (SXT) is the drug-of-choice in Stenotrophomonas maltophilia caused infections. There has been an increase in resistance to SXT of S. maltophilia over recent years. In this study 30 S. maltophilia clinical isolates resistant to SXT were investigated. Antibiotic susceptibilities for ciprofloxacin, moxifloxacin, levofloxacin, doxycycline, tigecycline, ceftazidime, colistin and chloramphenicol were determined by broth microdilution method. None of the strains were susceptible to ciprofloxacin, tigecycline, ceftazidime or colistin. Only 37% of the isolates were susceptible to levofloxacin or moxifloxacin. Two isolates resistant to all tested antibiotic agents and two others susceptible only to doxycycline were further investigated: susceptibility for combinations of antibiotics was analyzed by checkerboard technique. According to the fractional inhibitory concentration indices calculated, moxifloxacin plus ceftazidime combination was found to be synergistic in each case. Genetic testing revealed the predominance of sul1 gene. Our study concluded that the range of effective antibiotic agents is even more limited in infections caused by SXT-resistant S. maltophilia. In these cases, in vitro synergistic antibiotic combinations could be potential therapeutic options.

Honeydew honey as a potent antibacterial agent in eradication of multi‐drug resistant Stenotrophomonas maltophilia isolates from cancer patients

Multi-drug resistance in nosocomial pathogens is a continually evolving and alarming problem in health care units. Since ancient times, honey has been used successfully for the treatment of a broad spectrum of infections with no risk of resistance development. This study investigated the antibacterial activity of two natural honeys, namely honeydew and manuka, against 20 nosocomial multi-drug resistant Stenotrophomonas maltophilia (S. maltophilia) isolates from cancer patients. An antibiotic susceptibility test was carried out using the disk diffusion method with 20 antibiotic disks. The antibacterial activity of honey was determined using a broth dilution method. The concentration of honey used in the study was within the range of 3.75% to 25% (w/v). All 20 clinical isolates were multi-drug resistant against 11 to 19 antibiotics. The MICs for honeydew honey ranged from 6.25% to 17.5%, while those for active manuka honey ranged from 7.5% to 22.5%. Honeydew honey had lower MICs than manuka honey against 16 of the tested isolates. This study showed that Slovak honeydew honey has exceptional antibacterial activity against multi-drug resistant S. maltophilia isolates and was more efficient than manuka honey (UMF 15+). Honeydew honey with strong antibacterial activity could be used as a potential agent to eradicate multi-drug resistant clinical isolates.

Clinical Importance of Stenotrophomonas maltophilia Nosocomial Pneumonia Due to its High Mortality in Hemodialysis Patients

Patients undergoing hemodialysis are immunocompromised and can suffer from pneumonia with various pathogens in nosocomial conditions. We investigated the fundamental information on the characteristics of hemodialysis inpatients and nosocomial pneumonia. We surveyed 1803 hemodialysis patients admitted to our university hospital between 2001 and 2007. The mean patient age was 64.8 years and the average period of hospitalization was 28.1 days, which was considerably longer than the average stay in our hospital (14.2 days). Patients were admitted to many different departments and for various reasons. We isolated 391 microorganisms from the sputum of 120 pneumonia patients undergoing hemodialysis, including Candida albicans, methicillin-resistant Staphylococcus aureus, and Staphylococcus epidermidis, which were the leading three isolates. From these 120 patients, a total of 199 pathogens were identified as being responsible for the pneumonia. Multi-drug resistant Stenotrophomonas maltophilia was found to be susceptible to a new fluoroquinolone, but is resistant to older generation quinolones. Out of the 120 patients with pneumonia, 12 out of 18 patients infected with S. maltophilia died, indicating the highest fatality rate for this pathogen. In this survey, we found that hemodialysis patients were hospitalized for long periods, and for various reasons in many departments. They suffered from nosocomial pneumonia caused by multi-drug resistant pathogens, including S. maltophilia. For pneumonia due to S. maltophilia, new generation fluoroquinolones can be the treatment of choice, although S. maltophilia-related pneumonia should be treated very carefully because of its high fatality rate.

Risk Factors and Infection Prevention Measures for Multi-Drug Resistant Stenotrophomonas maltophilia Infection in a Surgical Intensive Care Unit

BACKGROUND/OBJECTIVES: During July-October 2004, surgical intensive care unit (SICU) personnel noted increased numbers of multi-drug resistant Stenotrophomonas maltophilia infections. An investigation was initiated to identify risk factors for infection and transmission and to recommend preventive and control measures.

Clinical Implications of Stenotrophomonas maltophilia Resistant to Trimethoprim-Sulfamethoxazole: a Study of 69 Patients at 2 University Hospitals

We conducted a retrospective case study at 2 tertiary care centers to determine the clinical implications of trimethoprim-sulfamethoxazole resistant Stenotrophomonas maltophilia (TSRSM). Of 69 reviewed cases (mean age, 57 y; male gender, 70%), 40 (58%) were classified as infections associated with TSRSM (respiratory tract, 14; soft tissue, 11; bloodstream, 8; other sites, 7). Severe underlying comorbidities (86%) and previous antibiotic exposure (99%) were common. Cefotetan (susceptibility, 55%), chloramphenicol (49%) and ticarcillin-clavulanate (45%) showed the highest in vitro activity against TSRSM, but were seldom used for therapy (7%). Among the 40 infected cases, 8 developed sepsis disorders and 8 died. Only 1 death could be directly attributed to autopsy-proven TSRSM infection (pneumonia). McCabe score (p = 0.03) and organ dysfunction (p = 0.006) were associated with an increased risk of death in infected patients; exposure to appropriate therapy tended to be protective against death (p = 0.08). 22 infected patients were treated medically; an additional procedure was necessary to clear the infection in 18 cases (surgery, 13; catheter removal, 5). Isolation precautions were rarely exercised, even in the presence of panresistant isolates. In summary, TSRSM-related infections occurred in severely ill patients with extensive exposure to the health-care system, and often required invasive procedures for cure. Infections were directly associated with severe morbidity, and tended to have an indirect rather than a direct impact on mortality.