Prevalence Of Multidrug-resistant Gram-negative Bacteria Research Articles

Prevalence of multidrug-resistant bacterial infections in diabetic foot ulcers: A meta-analysis.

Multidrug-resistant (MDR) bacterial infections have become increasingly common in recent years due to the increased prevalence of diabetic foot ulcers (DFUs). We carried out a meta-analysis aimed at investigating the prevalence of MDR bacteria isolated from DFUs and analysing the risk factors for MDR bacterial infection in patients with DFUs. The PubMed/Medline, Web of Science, Embase, Cochrane Library, Ovid, Scopus, and ProQuest databases were searched for studies published up to November 2023 on the clinical outcomes of MDR bacteria in DFUs. The main outcome was the prevalence of MDR bacteria in DFUs. A total of 21 studies were included, representing 4885 patients from which 2633 MDR bacterial isolates were obtained. The prevalence of MDR bacteria in DFUs was 50.86% (95% confidence interval (CI): 41.92%-59.78%). The prevalence of MDR gram-positive bacteria (GPB) in DFUs was 19.81% (95% CI: 14.35%-25.91%), and the prevalence of MDR gram-negative bacteria (GNB) in DFUs was 32.84% (95% CI: 26.40%-39.62%). MDR Staphylococcus aureus (12.13% (95% CI: 8.79%-15.91%)) and MDR Enterococcus spp. (3.33% (95% CI: 1.92%-5.07%)) were the main MDR-GPB in DFUs. MDR Escherichia coli, MDR Pseudomonas aeruginosa, MDR Enterobacter spp., MDR Klebsiella pneumoniae, and MDR Proteus mirabilis were the main MDR-GNB in DFUs. The prevalence rates were 6.93% (95% CI: 5.15%-8.95%), 6.01% (95% CI: 4.03%-8.33%), 3.59% (95% CI: 0.42%-9.30%), 3.50% (95% CI: 2.31%-4.91%), and 3.27% (95% CI: 1.74%-5.21%), respectively. The clinical variables of diabetic foot ulcer patients infected with MDR bacteria and non-MDR bacteria in the included studies were analysed. The results showed that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization and previous use of antibacterial drugs were significantly different between the MDR bacterial group and the non-MDR bacterial group. We concluded that there is a high prevalence of MDR bacterial infections in DFUs. The prevalence of MDR-GNB was greater than that of MDR-GPB in DFUs. MDR S. aureus was the main MDR-GPB in DFUs, and MDR E. coli was the main MDR-GNB in DFUs. Our study also indicated that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization, and previous use of antibacterial drugs were associated with MDR bacterial infections in patients with DFUs.

Prevalence of multidrug-resistant Gram-negative bacteria causing pyogenic infections at a tertiary care hospital in Haryana

Prevalence of multidrug-resistant Gram-negative bacteria causing pyogenic infections at a tertiary care hospital in Haryana

Prevalence of multidrug-resistant Gram-negative bacteria from blood cultures and rapid detection of beta-lactamase-encoding genes by multiplex PCR assay.

This study aimed to determine the prevalence of multidrug-resistant Gram-negative bacteria (GNB) from blood cultures in a tertiary-care hospital and the multiplex PCR assay's ability to detect resistance genes. A total of 388 GNB isolates obtained from hospitalized patients between November 2019 and November 2021 were included in the study. Antimicrobial susceptibility testing was done by VITEK 2 system and broth microdilution method. Beta-lactamase-encoding genes were detected by multiplex PCR assays, BioFire-Blood Culture Identification 2 (BCID2) panel (bioMérieux, France). Extended-spectrum beta-lactamases (ESBLs) were detected phenotypically with VITEK AST-GN71 card (bioMérieux, France). The isolates of GNB were classified into multidrug-resistant, extensively-drug-resistant, and pandrug-resistant categories, and their prevalence and distribution in different wards, including coronavirus diseases 2019 (COVID-19) intensive care units (ICU), were calculated. Results revealed that all isolates of Acinetobacter baumannii and Pseudomonas aeruginosa were multidrug-resistant as well as 91.6% of Enterobacter cloacae, 80.6% of Proteus mirabilis, and 76.1% of Klebsiella pneumoniae, respectively. In fermentative bacteria, blaOXA-48-like (58.1%), blaNDM (16.1%), blaKPC (9.7%) and blaVIM (6.5%) genes were detected. More than half of Enterobacter cloacae (58.3%) and Klebsiella pneumoniae (53.7%) produced ESBLs. Among non-fermenters, the blaNDM gene was carried by 55% of Pseudomonas aeruginosa and 19.5% of Acinetobacter baumannii. In the COVID-19 ICU, Acinetobacter baumannii was the most common isolate (86.1%). This study revealed high proportions of multidrug-resistant blood isolates and various underlying resistance genes in Gram-negative strains. The BCID2 panel seems to be helpful for the detection of the most prevalent resistance genes of fermentative bacteria.

Current Status of Endolysin-Based Treatments against Gram-Negative Bacteria.

The prevalence of multidrug-resistant Gram-negative bacteria is a public health concern. Bacteriophages and bacteriophage-derived lytic enzymes have been studied in response to the emergence of multidrug-resistant bacteria. The availability of tRNAs and endolysin toxicity during recombinant protein expression is circumvented by codon optimization and lower expression levels using inducible pET-type plasmids and controlled cultivation conditions, respectively. The use of polyhistidine tags facilitates endolysin purification and alters antimicrobial activity. Outer membrane permeabilizers, such as organic acids, act synergistically with endolysins, but some endolysins permeate the outer membrane of Gram-negative bacteria per se. However, the outer membrane permeation mechanisms of endolysins remain unclear. Other strategies, such as the co-administration of endolysins with polymyxins, silver nanoparticles, and liposomes confer additional outer membrane permeation. Engineered endolysins comprising domains for outer membrane permeation is also a strategy used to overcome the current challenges on the control of multidrug-resistant Gram-negative bacteria. Metagenomics is a new strategy for screening endolysins with interesting antimicrobial properties from uncultured phage genomes. Here, we review the current state of the art on the heterologous expression of endolysin, showing the potential of bacteriophage endolysins in controlling bacterial infections.

Efficacy of a coordinated strategy for containment of multidrug-resistant Gram-negative bacteria carriage in a Neonatal Intensive Care Unit in the context of an active surveillance program

BackgroundAntimicrobial resistance in neonatal intensive care unit (NICU) patients is a threat, due to the frequent use of antimicrobial treatment and invasive devices in fragile babies. Since 2014 an active surveillance program of multidrug-resistant Gram-negative bacteria (MDR-GNB) carriage has been in place in the five NICUs of Palermo, Italy. In 2017 an increase in the prevalence of MDR-GNB, and in particular of extended-spectrum β-lactamases-producing Klebsiella pneumoniae (ESBL-KP), was observed in “Civico” hospital NICU.AimTo assess the impact of a coordinated intervention strategy in achieving long-lasting reduction of MDR-GNB prevalence in the NICU.MethodsRectal swabs were obtained monthly and processed to detect MDR-GNB using standard methods. MDR-GNB were characterized by pulsed-field gel electrophoresis (PFGE). Since November 2017 the following intervention measures were applied: (a) two-months intensification of sample collection; (b) stakeholders meetings; (c) improvement of prevention measures and antimicrobial policies.FindingsDuring the intensified microbiological surveillance MDR-GNB and ESBL-KP were detected in rectal swabs (34.8%; 23.2%), nasal swabs (24.6%; 14.5%), oral swabs (14.5%; 5.4%), milk samples (32.1%; 17.9%), pacifiers swabs (30.8%; 17.9%) and from sub-intensive room surfaces. Thirteen ESBL-KP strains isolated from clinical and environmental samples showed identical PFGE patterns. The prevalence of MDR-GNB and ESBL-KP carriage significantly decreased in the year after intervention compared to the previous year (20.6% vs 62.2%; p < 0.001 and 11.1% vs 57.8%; p < 0.001). MDR-GNB were not detected at all for three months and ESBL-KP for five months. Multivariate analysis of the principal exposure variables showed that admission in the post-intervention period significantly reduced the risk of MDR-GNB carriage (adj-OR = 0.21, 95% CI = 0.076–0.629; p < 0.001).ConclusionsMDR-GNB broadly circulate in NICU setting, they can colonize different body sites and spread through various vehicles. A coordinated strategy of multiple interventions with active cooperation between epidemiologists and clinicians in the NICU can effectively reduce their circulation and in particular the carriage of the most dangerous ESBL-KP strains.

The Travelling Particles: Investigating microplastics as possible transport vectors for multidrug resistant E. coli in the Weser estuary (Germany)

The prevalence of multidrug-resistant Gram-negative bacteria in aquatic environments has been a long withstanding health concern, namely extended-spectrum beta-lactamase (ESBL) producing Escherichia coli. Given increasing reports on microplastic (MP) pollution in these environments, it has become crucial to better understand the role of MP particles as transport vectors for such multidrug-resistant bacteria. In this study, an incubation experiment was designed where particles of both synthetic and natural material (HDPE, tyre wear, and wood) were sequentially incubated at multiple sites along a salinity gradient from the Lower Weser estuary (Germany) to the offshore island Helgoland (German Bight, North Sea). Following each incubation period, particle biofilms and water samples were assessed for ESBL-producing E. coli, first by the enrichment and detection of E. coli using Fluorocult® LMX Broth followed by cultivation on CHROMAgar™ ESBL media to select for ESBL-producers. Results showed that general E. coli populations were present on the surfaces of wood particles across all sites but none were found to produce ESBLs. Additionally, neither HDPE nor tyre wear particles were found to harbour any E. coli. Conversely, ESBL-producing E. coli were present in surrounding waters from all sites, 64% of which conferred resistances against up to 3 other antibiotic groups, additional to the beta-lactam resistances intrinsic to ESBL-producers. This study provides a first look into the potential of MP to harbour and transport multidrug-resistant E. coli across different environments and the approach serves as an important precursor to further studies on other potentially harmful MP-colonizing species.

Pathogen Identification Direct From Polymicrobial Specimens Using Membrane Glycolipids

With the increased prevalence of multidrug-resistant Gram-negative bacteria, the use of colistin and other last-line antimicrobials is being revisited clinically. As a result, there has been an emergence of colistin-resistant bacterial species, including Acinetobacter baumannii and Klebsiella pneumoniae. The rapid identification of such pathogens is vitally important for the effective treatment of patients. We previously demonstrated that mass spectrometry of bacterial glycolipids has the capacity to identify and detect colistin resistance in a variety of bacterial species. In this study, we present a machine learning paradigm that is capable of identifying A. baumannii, K. pneumoniae and their colistin-resistant forms using a manually curated dataset of lipid mass spectra from 48 additional Gram-positive and -negative organisms. We demonstrate that these classifiers detect A. baumannii and K. pneumoniae in isolate and polymicrobial specimens, establishing a framework to translate glycolipid mass spectra into pathogen identifications.

Cost of hospitalised patients due to complicated urinary tract infections: a retrospective observational study in countries with high prevalence of multidrug-resistant Gram-negative bacteria: the COMBACTE-MAGNET, RESCUING study

ObjectiveComplicated urinary tract infections (cUTIs) impose a high burden on healthcare systems and are a frequent cause of hospitalisation. The aims of this paper are to estimate the cost per...

Phenotypic and Genomic Characterization of AmpC-Producing Klebsiella pneumoniae From Korea

The prevalence of multidrug-resistant gram-negative bacteria has continuously increased over the past few years; bacterial strains producing AmpC β-lactamases and/or extended-spectrum β-lactamases (ESBLs) are of particular concern. We combined high-resolution whole genome sequencing and phenotypic data to elucidate the mechanisms of resistance to cephamycin and β-lactamase in Korean Klebsiella pneumoniae strains, in which no AmpC-encoding genes were detected by PCR. We identified several genes that alone or in combination can potentially explain the resistance phenotype. We showed that different mechanisms could explain the resistance phenotype, emphasizing the limitations of the PCR and the importance of distinguishing closely-related gene variants.

Antibiotic stewardship : Aprogrammatic approach to improved antimicrobial management

Due to the increasing selection and prevalence of multidrug-resistant gram-negative bacteria and the insufficient development of novel antibiotics, the responsible and prudent use of the available antimicrobial drugs is of major importance. In Germany the rational use of anti-infectives considering the local antimicrobial resistance situation is defined in the infection protection act of 2011. An important tool to follow legal regulations and to improve the treatment of bacterial infections is the antimicrobial stewardship (AMS) concept. Hospitals implementing an AMS program charge amultidisciplinary team of experts to develop and monitor treatment standards and to establish asystem of regular consultations and ward rounds. Objectives of this set of measures are the optimization of the individual treatment outcome and on alonger range the improvement of the epidemiological situation. AMS programs include all clinical disciplines that use antimicrobials. Trauma surgery is also affected in aspecial way as soon as complicated infections and those with multidrug-resistant bacteria are treated.

ESBL- and Carbapenemase-Producing Enterobacteriaceae in Patients with Bacteremia, Yangon, Myanmar, 2014

Among 42 gram-negative bloodstream isolates from inpatients in 3 hospitals in Yangon, Myanmar, admitted during July–December 2014, 16 (38%) were extended-spectrum β-lactamase–producing Enterobacteriaceae and 6 (14%) produced carbapenemase. The high prevalence of multidrug-resistant gram-negative bacteria raises concerns about the empiric treatment of patients with sepsis in Yangon.

Prevalence of multidrug-resistant gram-negative bacteria among nursing home residents: A systematic review and meta-analysis.

Multidrug-resistant gram-negative bacteria (MDR-GNB) are associated with an increasing proportion of infections among nursing home (NH) residents. The objective of this systematic review and meta-analysis was to critically review evidence of the prevalence of MDR-GNB among NH residents. Following Meta-Analysis of Observational Studies in Epidemiology guidelines, a systematic review of literature for the years 2005-2016 using multiple databases was conducted. Study quality, appraised by 2 reviewers, used Downs and Black risk of bias criteria. Studies reporting prevalence of MDR-GNB colonization were pooled using a random effects meta-analysis model. Heterogeneity was assessed using Cochran Q and I2 statistics. Of 327 articles, 12 met the criteria for review; of these, 8 met the criteria for meta-analysis. Escherichia coli accounted for the largest proportion of isolates. Reported MDR-GNB colonization prevalence ranged from 11.2%-59.1%. Pooled prevalence for MDR-GNB colonization, representing data from 2,720 NH residents, was 27% (95% confidence interval, 15.2%-44.1%) with heterogeneity (Q = 405.6; P = .01; I2 = 98.3). Two studies reported MDR-GNB infection rates of 10.9% and 62.7%. Our findings suggest a high prevalence of MDR-GNB colonization among NH residents, emphasizing the need to enhance policies for infection control and prevention (ICP) in NHs.

Presence, distribution and molecular epidemiology of multi-drug-resistant Gram-negative bacilli from medical personnel of intensive care units in Tianjin, China, 2007–2015

Multi-drug-resistant Gram-negative bacteria (MDRGNB) have become an important cause of nosocomial infection in intensive care units (ICUs). To investigate the molecular epidemiology of MDRGNB isolated from medical personnel (MP) and non-medical personnel (NMP) at 69 ICUs in Tianjin, China. From April 2007 to October 2015, 2636 nasal and hand swab samples from 1185 MP and 133 NMP were cultured for GNB (including MDRGNB), meticillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). The susceptibilities of GNB to 14 antimicrobial agents were determined, and 80 MDRGNB were characterized using pulsed-field gel electrophoresis (PFGE) and dendrogram analysis. In total, 301 GNB were identified in 269 MP, including 109 MDRGNB isolates in 104 MP. Forty-two GNB were isolated from 39 NMP, which included 20 NMP with MDRGNB. Overall, 8.8% of MP were colonized with MDRGNB, which greatly exceeded colonization rates with MRSA (0.9%) and VRE (0.1%). Three pairs of Klebsiella pneumoniae and one pair of Enterobacter aerogenes were indistinguishable from each other, but the majority of isolate tests had distinct PFGE profiles. The prevalence of MDRGNB was high among ICU MP in Tianjin, and greatly exceeded that of VRE and MRSA. There was no difference in the rates of nasal carriage of MDRGNB between MP and NMP, but NMP were significantly more likely to have hand colonization with MDRGNB. PFGE profiles showed that there was only limited sharing of strains of MDR E. aerogenes and K.pneumoniae between personnel.

Multidrug-resistant organisms (MDRO) in patients in outpatient care in the Rhine-Main region, Germany, in 2014: Prevalence and risk factors

Data on the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in outpatient care are scarce and those on the prevalence of multidrug-resistant Gram-negative bacteria (MRGN) are lacking completely. Therefore, the network on multidrug-resistant organisms (MDRO) in the Rhine-Main region (MRE-Netz Rhein-Main) performed a multicenter study on current prevalence data and risk factors for MDRO. Characteristics of all patients were obtained according to a modified healthcare-associated infections in long-term care facilities (HALT) questionnaire and swabs from the nares/throat and anus were tested for MRSA and extended-spectrum beta-lactamase (ESBL)/MRGN. Risk factors were calculated via odds ratios. Ten nursing services with 486 patients participated in this study, 269 patients agreed to having swabs of the nares/throat taken, and 132 patients had anal swabs. MRSA was detected in 3.7%, and ESBL/MRGN in 14.4% of the patients (6.8% ESBL, 7.6% MRGN, 0% MRGN). Risk factors for MRSA were high dependency on care (stage 3 or above; OR 5.1), antibiotic use during the preceding 3 months (O R 3.7), hospital stay during the last 6 months (OR 4.3), and a positive history for MRSA (OR 18.1). Incontinence and preceding hospital stays proved to be risk factors for ESBL colonization (OR 9.5 or 6.5), whereas risk factors for MRGN colonization were a high level of care dependency (OR 7.5), urinary catheter (OR 8.3), percutaneous endoscopic gastrostomy tube and other stomata (OR 6.2), and artificial respiration (OR 5), in addition to a positive history for MRSA (OR 20) and ESBL (OR 6.7). Considering the high prevalence of colonization with MDRO in outpatient care, nursing services must be competent in caring for such patients: good hygiene procedures, including hand hygiene and appropriate handling in wound management, punctures and injections, with catheters, stomata, and if necessary with artificial respiration should be practiced. The guidelines of the German Commission on hospital hygiene and infection prevention should also be observed.

Effects of a Carbapenem De-escalation Antibiotic Stewardship Program

In regions with a high prevalence of multidrug-resistant gram-negative bacteria, carbapenems are appropriate for empirical treatment of serious

Successful use of gentamycin as an antibiotic prophylaxis regimen to reduce the rate of healthcare-associated infections after renal transplantation

At our institution, we observed an increase in the incidence of healthcare-associated infections (HAI) due to Gram-negative bacilli, including three cases of carbapenem-resistant Klebsiella pneumoniae, among patients who underwent renal transplantation. In addition to strengthening infection control measures, we chose to add gentamycin to the antibiotic prophylaxis regimen of patients undergoing renal transplantation. We assessed the number of HAI occurring within 30 days of renal transplantation during two time periods: (1) the pre-intervention period, between September 2009 and June 2010, and (2) the post-intervention period, between July 2010 and April 2011. The intervention consisted of the addition of gentamycin to the surgical antibiotic prophylaxis regimen. The percentage of patients with HAIs was 31% lower during the post-intervention period (p=0.03), with the greatest reductions observed for urinary tract infections (p=0.024). Carbapenem-resistant K. pneumoniae was not isolated during this period. The investigated patients did not exhibit worsening renal function. Further studies are needed to assess antibiotic prophylaxis in renal transplantation patients at institutions where there is a high prevalence of multidrug-resistant Gram-negative bacteria.

Multidrug-Resistant Gram-Negative Bacteria at a Long-Term Care Facility: Assessment of Residents, Healthcare Workers, and Inanimate Surfaces

To characterize the clinical and molecular epidemiology of multidrug-resistant (MDR) organisms in residents, in healthcare workers (HCWs), and on inanimate surfaces at a long-term care facility (LTCF). Point-prevalence study in 4 separate wards at a 600-bed urban LTCF that was conducted from October 31, 2006 through February 5, 2007. One hundred sixty-one LTCF residents and 13 HCWs. Nasal and rectal samples were obtained for culture from each resident, selected environmental surfaces in private and common rooms, and the hands and clothing of HCWs in each ward. All cultures were evaluated for the presence of MDR gram-negative bacteria, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococci. Clinical and demographic information were collected for each enrolled resident. Molecular typing was performed to identify epidemiologically related strains. A total of 37 (22.8%), 1 (0.6%), and 18 (11.1%) residents were colonized with MDR gram-negative bacteria, vancomycin-resistant enterococci, and methicillin-resistant S. aureus, respectively. MDR gram-negative bacteria were recovered from 3 (1.8%) of the 175 environmental samples cultured, all of which were obtained from common areas in LTCF wards. One (7.7%) of the 13 HCWs harbored MDR gram-negative bacteria. Molecular typing identified clonally related MDR gram-negative strains in LTCF residents. After multivariable analysis, length of hospital stay of at least 4 years, fecal incontinence, and antibiotic exposure for at least 8 days were independent risk factors associated with harboring MDR gram-negative bacteria among LTCF residents. The prevalence of MDR gram-negative bacteria is high among LTCF residents and exceeds that of vancomycin-resistant enterococci and methicillin-resistant S. aureus. Common areas in LTCFs may provide a unique opportunity for person-to-person transmission of MDR gram-negative bacteria.

Comment on: Development and validation of a reversed-phase high-performance liquid chromatography assay for polymyxin B in human plasma

Sir, We read with great interest the article by Cao et al. on the development of a reversed-phase HPLC assay for polymyxin B in human plasma. The research group from the Facility for Anti-Infective Drug Development and Innovation (FADDI) should be commended for their sustained contribution to understanding the pharmacology of polymyxins over the years. However, before this assay can be adopted widely for pharmacokinetic studies, several issues need to be discussed. First, we corroborate with Cao et al. that the prevalence of multidrug-resistant Gram-negative bacteria is on the rise and polymyxin B is increasingly used as the last viable therapeutic option. The pharmacokinetics of polymyxin B remains poorly understood; the most commonly used dosing regimens are often based on convention rather than being supported by pharmacokinetics and pharmacodynamics. Commercial formulations of polymyxin B contain multiple components. Current quality control procedures focus on overall antimicrobial activity, rather than on the proportion of each component. Therefore, manufacturing lot-to-lot variation in the composition of the polymyxin B components may exist. In addition, patients with multidrugresistant bacterial infections are often given other antimicrobial agents concurrently. Consequently, we agree that using a microbiological assay to detect polymyxin B in clinical samples may not be very satisfactory. Our group has also been working on the pharmacokinetics and pharmacodynamics of polymyxin B over the years. The complete assay is still under development, but several key points have been learnt. Polymyxin B1 was found to be the major component among more than 30 other components (e.g. polymyxin B2, B3 etc.) present in the complex. Using our HPLC-MS assay, a typical chromatogram of polymyxin B (USP) detecting several of these components is shown in Figure 1. In contrast, the chromatography used by Cao et al. (Figure 2 of the article) may not have the desired resolution to distinguish these closely related polymyxin B components. Without an optimal chromatographic separation, using mass-charge ratios to confirm the identity of various polymyxin B components may also be misleading. As shown in Figure 1, polymyxin B1 and B5 have an identical mass-charge ratio, as well as polymyxin B2 and B3. Second, as analytical grade forms of each of these components are presently not commercially available, a relative method of quantification was used. In view of the possible lot-to-lot variations in the relative composition of various polymyxin B components, for the assay to be useful to quantify polymyxin B concentration in a patient, the same mixture of known total quantity (formulation batch) should be used as the reference standard. We are unsure if this is practical as: (i) different patients may be given different manufacturing lots of polymyxin B; and (ii) the same patient may also be given different manufacturing lots of polymyxin B during a course of therapy. As a result, multiple lots of reference standards may have to be used in a study. Finally, it is unclear to us if each polymyxin B component has different antimicrobial activity, pharmacokinetic property and propensity for toxicity. Consequently, the validity of correlating the sums of polymyxin B1 and B2 peaks to ‘total polymyxin B’ may be questionable. By characterizing the pharmacokinetics of total polymyxin B concentrations over time, a more rapid clearance of one component could have been compensated by a more gradual clearance of its counterpart. Until the antimicrobial activity and pharmacokinetics of polymyxin B1 and B2 can be proved to be identical, it may be prudent to characterize them as separate entities. With a better understanding of its pharmacokinetics, we are hopeful that the dosing regimens of polymyxin B could be designed more rationally in the future to improve patient outcomes and avoid toxicity. There is still much to be learnt about polymyxin B. It is our expectation that this communication will encourage clinicians and other investigators to examine these