Nanotechnology using nanoscale materials is increasingly being utilized for clinical applications, especially as a new paradigm for infectious diseases. Infections caused by multidrug-resistant organisms (MDROs) are emerging as causes of morbidity and mortality worldwide. Antibiotic options for infections caused by MDROs are often limited. These clinical challenges highlight the critical demand for alternative and effective antimicrobial strategies. Nanoparticles (NPs) can penetrate the cell membrane of pathogenic microorganisms and interfere with important molecular pathways, formulating unique antimicrobial mechanisms. In combination with optimal antibiotics, NPs have demonstrated synergy and may aid in limiting the global crisis of emerging bacterial resistance. In this review, we summarized current research on the broad classification of the NPs that have shown in vitro antimicrobial activity against MDROs, including the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). The pharmacokinetics and pharmacodynamic characteristics of NPs and bacteria-resistant mechanisms to NPs were also discussed.

: Background.  Klebsiella pneumoniae, a Gram‐negative bacillus usually forming glistening mucoid colonies with viscid consistency on the culture plate, is a common pathogen causing various clinical infection patterns. However, little is known about the clinical implications of this mucoid character.Objective.  The purposes of this study, therefore, were to investigate the frequency of hypermucoviscosity (HV) in bacteraemic isolates of K. pneumoniae, and determine the significance of any association between HV and various clinical manifestations.Design.  Retrospective observational study.Patients.  Patients diagnosed with K. pneumoniae bacteraemia at a community‐based university hospital between June 1999 and June 2001 were enrolled in this analysis.Measurements.  Clinical data concerning comorbid diseases and infection patterns was collected. K. pneumoniae bacteraemic isolates were examined for the presence of HV using a modified string test. The clinical impact of HV and risk factors for the invasive syndrome were assessed using statistical analysis. Polymerase chain reaction (PCR) was performed to detect magA, a gene related to HV phenotype.Results.  Overall, 200 (64.9%) of the 308 cases of K. pneumoniae bacteraemia were community‐acquired infections. Compared with hospital‐acquired K. pneumoniae bacteraemia (HA‐KpB), community‐acquired K. pneumoniae bacteraemia (CA‐KpB) was more likely to be monomicrobial in nature (83.5% vs. 64.8%; P < 0.001) and caused by HV strains (41.5% vs. 14.8%; P < 0.001). The prevalence rate of magA among HV phenotypical K. pneumoniae strains was 24.1%. Patients infected with HV‐positive strains were more likely to have the distinctive invasive syndrome (i.e. liver abscess, meningitis, pleural empyaema or endophthalmitis) than those infected with HV‐negative variants (37.3% vs. 6.8%; P < 0.001). Multivariate logistic regression analysis, adjusted for age, showed that HV phenotype in K. pneumoniae strains (OR 8.86; 95% CI, 3.70–21.25; P < 0.001) was positively associated with the development of the invasive syndrome in CA‐KpB cases.Conclusions.  The HV phenotype of K. pneumoniae bacteraemic isolates was associated with the development of a distinctive invasive syndrome. Identification of the HV phenotype should prompt clinicians to initiate aggressive investigations for invasive diseases.

Objective.: To investigate the impact of antimicrobial resistance on clinical and economic outcomes among hospitalized patients with multidrug-resistant (MDR) Acinetobacter baumannii bacteremia.Design.: A retrospective, matched-cohort study.Setting.: A tertiary care university teaching hospitalMethods.: A matched case-control (1:1) study was conducted to compare the differences in clinical and economic outcomes of patients with MDR A. baumannii bacteremia and patients with non-MDR A. baumannii bacteremia. Case patients were matched to control patients on the basis of sex, age, severity of underlying and acute illness, and length of hospital stay before onset of bacteremia.Results.: Forty-six (95.8%) of 48 cases with MDR A. baumannii bacteremia were eligible for the study and matched with appropriate controls. The sepsis-related mortality rate was 34.8% among cases and 13.0% among controls, for an attributable mortality rate of 21.8% (adjusted odds ratio, 4.1 [95% confidence interval, 1.1-15.7]; P = .036). After the onset of bacteremia, cases and controls had a significantly different length of hospital stay (54.2 vs 34.1 days; P = .006), hospitalization cost (US$9,349 vs US$4,865; P = .001 ), and antibiotic therapy cost (US$2,257 vs US$1,610; P = .014). Thus, bacteremia due to MDR A. baumannii resulted in 13.4 days of additional hospitalization and US$3,758 of additional costs, compared with bacteremia due to non-MDR A. baumannii.Conclusions.: Patients with MDR A. baumannii bacteremia had a higher mortality rate and incurred greater medical costs than patients with non-MDR A. baumannii bacteremia.

Background. Extended-spectrum ß-lactamase (ESBL)–producing Enterobacteriaceae isolates are important clinical pathogens. In addition, the efficacy of cefepime for such infections is controversial. Methods. We performed a retrospective study of monomicrobial bacteremia caused by ESBL producers at 2 medical centers between May 2002 and August 2007. The patients definitively treated with in vitro active cefepime (cases) were compared with those treated with a carbapenem (controls) in a propensity score–matched analysis to assess therapeutic effectiveness. The 30-day crude mortality is the primary endpoint. Results. A total of 178 patients were eligible for the study. Patients who received cefepime (n = 17) as definitive therapy were more likely to have a clinical failure (odds ratio [OR] 6.2; 95% confidence interval [CI], 1.7–22.5; P = .002), microbiological failure (OR 5.5; 95% CI, 1.3–25.6; P = .04), and 30-day mortality (OR 7.1; 95% CI, 2.5–20.3; P < .001) than those who received carbapenem therapy (n = 161). Multivariate regression revealed that a critical illness with a Pitt bacteremia score ≥4 points (OR 5.4; 95% CI, 1.4–20.9; P = .016), a rapidly fatal underlying disease (OR 4.4; 95% CI, 1.5–12.6; P = .006), and definitive cefepime therapy (OR 9.9; 95% CI, 2.8–31.9; P < .001) were independently associated with 30-day crude mortality. There were 17 case-control pairs in the propensity scores matched analysis. The survival analysis consistently found that individuals who received cefepime therapy had a lower survival rate (log-rank test, P = .016). Conclusions. Based on the current Clinical and Laboratory Standards Institute susceptible breakpoint of cefepime (minimum inhibitory concentration ≤8 μg/mL), cefepime definitive therapy is inferior to carbapenem therapy in treating patients with so-called cefepime-susceptible ESBL-producer bacteremia.

Aeromonas dhakensis was first isolated from children with diarrhea in Dhaka, Bangladesh and described in 2002. In the past decade, increasing evidence indicate this species is widely distributed in the environment and can cause a variety of infections both in human and animals, especially in coastal areas. A. dhakensis is often misidentified as A. hydrophila, A. veronii or A. caviae by commercial phenotypic tests in the clinical laboratory. Correct identification relies on molecular methods. Increasingly used matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) may be able to identify Aeromonas specie rapidly and accurately. A. dhakensis has shown its potent virulence in different animal models and clinical infections. Although several virulence factors had been reported, no single mechanism is conclusive. Characteristically A. dhakensis is the principal species causing soft tissue infection and bacteremia, especially among patients with liver cirrhosis or malignancy. Of note, A. dhakensis bacteremia is more lethal than bacteremia due to other Aeromonas species. The role of this species in gastroenteritis remains controversial. Third generation cephalosporins and carbapenems should be used cautiously in the treatment of severe A. dhakensis infection due to the presence of AmpC β-lactamase and metallo-β-lactamase genes, and optimal regimens may be cefepime or fluoroquinolones. Studies of bacterial virulence factors and associated host responses may provide the chance to understand the heterogeneous virulence between species. The hypothesis A. dhakensis with varied geographic prevalence and enhanced virulence that compared to other Aeromonas species warrants more investigations.