Multiresistant Gram-negative Bacilli Research Articles

Epidemiology of multi-resistant Gram-negative bacilli (MRGNR) in Great Western NSW

Epidemiology of multi-resistant Gram-negative bacilli (MRGNR) in Great Western NSW

Antibiotics in development for multiresistant gram-negative bacilli

The rapid increase in antibiotic(ATB) resistance among Gram-negative bacilli(BGN), especially in strains of Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii, with high resistance patterns (XDR), poses a huge threat to health systems worldwide.In the last decade, different ATBs have been developed against XDR, some of which combine a lactam β along with a β-lactamase inhibitor, while others use non-β-lactam inhibitors. Most of them have adequate “in vitro” activity on several β-lactamases of class A, C and D of Ambler. However, combinations such as Ceftazidime/avibactam, Ceftolozane/Tazobactam and Meropenem/vaborbactam have no activity against metallo-β-lactamases(MβL). New combinations such as Aztreonan/AVI, Cefepime/Zidebactam, or new cephalosporins such as Cefiderocol, have efficacy against MβL enzymes. Although some of these combinations are already approved and in the commercialization phase, many of them have yet to define their place within the treatment of microorganisms with high resistance through clinical studies.

The problem of multi-resistance in gram-negative bacilli in intensive care units: Treatment and prevention strategies

The rise of infections caused by multi-resistant gram-negative bacilli (MR-GNB), which includes carbapenems, represents one of the major current challenges worldwide. These MR-GNB include extended spectrum β-lactamase-producing Enterobacterales, derepressed AmpC-producing or carbapenemase-producing Enterobacterales as well as non-fermenting Gram-negative bacilli such as Pseudomonas aeruginosa or Acinetobacter baumannii. P. aeruginosa predominantly exhibits other resistance mechanisms different to β-lactamases such as expulsion pumps or loss of porins. A. baumannii frequently presents several of these resistance mechanisms. Mortality is high especially if empirical treatment is inadequate. In this review, treatment strategies are revised, describing the tools available to identify patients in whom empirical antibiotic treatment would be justified to cover MR-GNB, the importance of optimizing the administration of these antibiotics, as well as prevention strategies to avoid its spread from patients colonized or infected by a MR-GNB.

Characterization of multiresistant gram-negative bacilli, isolated in patients hospitalized in health institutions in Barranquilla (Colombia)

The emergence of carbapenem resistant gramnegative bacilli has become a problem of public health worldwide, because it is associated with high mortality rates, increased levels of resistance to other antimicrobials, increased potential for dissemination transition and increase in health care costs. To characterize multiresistant gram-negative bacilli, isolated in patients hospitalized in health institutions of Barranquilla (Colombia). A descriptive study was conducted on the phenotypic and genotypic characterization of bacterial resistance in infections associated with health care, mediated by carbapenemases in bacterial isolates sent by laboratories belonging to the laboratory network of the Department of Atlántico. KPC was the most frequent carbapenemase in Enterobacterales (27.6%), predominantly in Klebsiella pneumoniae (13.1%) alone and associated with other carbapenemases. In Pseudomonas aeruginosa, VIM carbapenemase (32.8%) predominated and OXA in Acinetobacter baumannii (17.1%). A wide distribution of multi-resistant strains producing carbapenemases in Atlantic health institutions was found, which expressed the following resistance mechanisms: KPC, VIM, NDM, OXA.

Effect of Water Chlorination on Development and Persistence of Biofilm in Shower Heads

Background: A cluster of sternal surgical site infections caused by Pseudomonas aeruginosa led to sampling of shower heads in patient rooms. Multiple subtypes of Pseudomonas aeruginosa were found and were genetically diverse from the patient isolates. Visible biofilm was found in showerheads in the cardiothoracic ward. Ways of minimizing formation and persistence of biofilm in the shower heads were sought. Methods: A low-dose chlorination dosing system was introduced in September 2018 to the circulating warm-water system supplying the building block where the cardiac surgery ward is situated. Of the 145 showers in that block, 70 shower heads were sampled and the shower heads were replaced. Of these, 35 were sampled at 3 months and 35 were tested at 6 months (biofilm prevention group). Of the remaining 70 shower heads, 35 were tested at 3 months and 35 at 6 months (biofilm removal group). Heterotrophic colony count (HCC) in CFU/mL was chosen as the outcome measure. Analysis was conducted in accordance with AS 4276.3.2 (2003). The microbial growth data followed a log-normal distribution due to the exponential growth of bacteria. The natural log of the data was therefore calculated, and results from each period were compared using analysis of variance (ANOVA). Free chlorine residual levels were controlled using a combination of feed-forward and oxidation reduction potential (ORP) feedback control, and levels were retested and adjusted during the review period using N,N-diethyl-p-phenylenediamine (DPD) chemistry. Results: Mean and median levels of log HCC data are shown in Fig. 1. We detected a statistically significant difference in HCC between the 6-month-old untreated shower heads (group B) and treated shower heads (Group D) (P < .001). Hypochlorite was generally dosed at a concentration of 0.5 mg/L free chlorine for the first 3 months, and 1.5 mg/L for the second 3 months. Approximately 65% of the chlorine was lost as it travelled around the system. Discussion: Waterborne pathogens, especially multiresistant Gram-negative bacilli, have been increasingly recognized as hospital-acquired pathogens. Many instances of the transmission of these pathogens have been reported, from premise plumbing to patients, and have been confirmed using molecular typing techniques. Conclusions: A low-dose chlorination system of the circulating warm-water supply seemed effective in preventing biofilm formation and reducing existing biofilm in shower heads using HCCs as a measure of biofilm. This information adds to the potential armamentarium for controlling the spread of these waterborne pathogens.Funding: NoneDisclosures: None

Bloodstream infections caused by multidrug-resistant gram-negative bacteria: epidemiological, clinical and microbiological features

BackgroundBloodstream infections (BSI) are associated with high morbidity and mortality. This scenario worsens with the emergence of drug-resistant pathogens, resulting in infections which are difficult to treat or even untreatable with conventional antimicrobials. The aim of this study is to describe the epidemiological aspects of BSI caused by multiresistant gram-negative bacilli (MDR-GNB).MethodsWe conducted a laboratory-based surveillance for gram-negative bacteremia over a 1-year period. The bacterial isolates were identified by MALDI-TOF/MS and the antimicrobial susceptibility testing was performed by VITEK®2. Resistance genes were identified through PCR assays.ResultsOf the 143 patients, 28.7% had infections caused by MDR-GNB. The risk factors for MDR bacteremia were male sex, age ≥ 60, previous antimicrobial use, liver disease and bacteremia caused by K. pneumoniae. K. pneumoniae was the most frequently observed causative agent and had the highest resistance level. Regarding the resistance determinants, SHV, TEM, OXA-1-like and CTX-M-gp1 were predominant enzymatic variants, whereas CTX-M-gp9, CTX-M-gp2, KPC, VIM, GES, OXA-48-like, NDM and OXA-23-like were considered emerging enzymes.ConclusionsHere we demonstrate that clinically relevant antibiotic resistance genes are prevalent in this setting. We hope our findings support the development of intervention measures by policy makers and healthcare professionals to face antibiotic resistance.

Resistência à Colistina em isolados de hemoculturas de recém-nascidos admitidos em um hospital escola

O objetivo deste estudo foi avaliar a resistência frente à colistina em isolados de hemoculturas de recém-nascidos (RN) admitidos em um Hospital Escola no período de 4 anos. Os testes de identificação e os perfis de sensibilidade frente aos antimicrobianos foram realizados através de sistemas automatizados. No período deste estudo, 923 hemoculturas foram positivas, 92,09% (850/923) causadas por microrganismos Gram-positivos e 7,91% (73/923) por Gram-negativos. Destas, dois isolados foram resistentes à colistina: Acinetobacter baumannii e Sphingomonas paucimobilis; e um isolado de Pseudomonas aeruginosa mostrou perfil intermediário a este antimicrobiano, apresentando também significativa resistência aos carbapenêmicos. Este perfil é preocupante uma vez que estes antimicrobianos constituem a última alternativa para o tratamento de infecções causadas por bacilos Gram-negativos multirresistentes. Os resultados deste estudo sinalizam para o seguimento do monitoramento desta resistência.

Pressure ulcer as a reservoir of multiresistant Gram-negative bacilli: risk factors for colonization and development of bacteremia

The purpose of this study was to identify the risk factors that predispose patients who are hospitalized with pressure ulcers (PUs) colonized by Gram-negative bacilli (GNB) to develop bacteremia. In addition, we also detected main phenotypes of resistance in infected and uninfected PUs. A prospective cohort study was conducted at the Clinical Hospital of the Federal University of Uberlândia including patients with Stage II or greater PUs, colonized or not with GNB, from August 2009 to July 2010. Infected ulcers were defined based on clinical signs and on positive evaluation of smears of wound material translated by a ratio of polymorphonuclear cells to epithelial cells ≥2:1, after Giemsa staining. A total of 60 patients with Stage II PUs were included. Of these 83.3% had PUs colonized and/or infected. The frequency of polymicrobial colonization was 74%. Enterobacteriaceae and GNB non-fermenting bacteria were the most frequent isolates of PUs with 44.0% of multiresistant isolates. Among patients who had infected PUs, six developed bacteremia by the same microorganism with a 100% mortality rate. In addition, PUs in hospitalized patients were major reservoir of multiresistant GNB, also a high-risk population for the development of bacteremia with high mortality rates.

Efficacy and Toxicity of High-Dose Colistin in Multidrug-Resistant Gram-Negative Bacilli Infections: A Comparative Study of a Matched Series

Background: Colistimethate sodium (CMS) is the commercialized form of colistin that is effective against multiresistant Gram-negative bacilli. Its main side effects are nephrotoxicity and neurotoxicity. Pharmacodynamic dosages showed that they were infratherapeutic. Therefore, strategies with higher doses were proposed. The aim of this study was to assess the efficiency and toxicity of higher-dose CMS by comparing two treatment strategies: high-dose CMS versus standard-dose CMS. Methods: A prospective and comparative study of two matched groups was conducted. Fourty-six patients in each group were matched for age, severity and nature of infection. In the high-dose colistin group, CMS was administered at a loading dose of 9 MIU followed by a maintenance dose of 4.5 MIU/12 h. In the second group, retrospectively analyzed, colistin was administered at 6 MIU/day. For each group, clinical results, bacteriological eradication and daily creatinine clearance were recorded. Primary outcome measures were clinical cure defined as disappearance of infectious signs and eradication of microorganisms in all the follow-up cultures. Secondary outcome measures were incidence of acute renal failure and mortality. Results: Ninety-two patients were analyzed by matching. There was a higher cure rate in the high-dose group (63 vs. 41.3%, p = 0.04). No higher risk of nephrotoxicity was found by increasing daily doses of colistin (32.2 versus 26%, p = 0.64). Similarly, there was no significant difference in the time to onset of renal failure (8.32 vs. 11 days, p = 1) or in the requirement of hemodialysis (26.6 vs. 41%, p = 1). Conclusion: The high-dose colistin regimen is more efficient, without significant renal or neurological toxicity.

Managing a nosocomial outbreak of carbapenem-resistant Klebsiella pneumoniae: an early Australian hospital experience.

Carbapenems are traditionally reserved as the last line of defence for treatment of serious infections with multiresistant Gram-negative bacilli. Reports of Klebsiella pneumoniae carbapenemase (KPC)-producing organisms have been emerging globally, but rare in Australasia to date. We describe an outbreak of KPC-2 producing K. pneumoniae at an Australian hospital. After initial detection in October 2012, a retrospective review of patients with meropenem-resistant K. pneumoniae to June 2012, and ongoing prospective surveillance, was undertaken. Included patients were admitted to the hospital after June 2012 and had meropenem-resistant K. pneumoniae isolated from any site. Available isolates underwent detection of the KPC-2 gene by polymerase chain reaction and molecular typing was performed to determine genetic relatedness between isolates. Point-prevalence screening was performed on selected wards to detect asymptomatic carriage. Infection control procedures were implemented to contain the outbreak. Ten cases were identified in the initial cluster. Eight were localised to a single inpatient ward. Point-prevalence screening revealed one extra case. After temporary containment, re-emergence of KPC-producing isolates was observed post October 2013 with 18 further cases identified. Four K. pneumoniae isolates in the 2012 cluster and 16 from the 2013-2014 cluster were referred for further testing. All carried the KPC-2 beta-lactamase gene. The 2012 isolates were genetically similar to the 2014 isolates. KPC-2 mediated resistance is an emerging threat in Australia. The re-emergence of KPC despite initial containment emphasises the need for constant vigilance in the microbiology laboratory and ongoing maintenance of infection control and antimicrobial stewardship activity.

Controlling hospital-acquired infection: focus on the role of the environment and new technologies for decontamination.

There is increasing interest in the role of cleaning for managing hospital-acquired infections (HAI). Pathogens such as vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), multiresistant Gram-negative bacilli, norovirus, and Clostridium difficile persist in the health care environment for days. Both detergent- and disinfectant-based cleaning can help control these pathogens, although difficulties with measuring cleanliness have compromised the quality of published evidence. Traditional cleaning methods are notoriously inefficient for decontamination, and new approaches have been proposed, including disinfectants, steam, automated dispersal systems, and antimicrobial surfaces. These methods are difficult to evaluate for cost-effectiveness because environmental data are not usually modeled against patient outcome. Recent studies have reported the value of physically removing soil using detergent, compared with more expensive (and toxic) disinfectants. Simple cleaning methods should be evaluated against nonmanual disinfection using standardized sampling and surveillance. Given worldwide concern over escalating antimicrobial resistance, it is clear that more studies on health care decontamination are required. Cleaning schedules should be adapted to reflect clinical risk, location, type of site, and hand touch frequency and should be evaluated for cost versus benefit for both routine and outbreak situations. Forthcoming evidence on the role of antimicrobial surfaces could supplement infection prevention strategies for health care environments, including those targeting multidrug-resistant pathogens.

Predictors of use of infection control precautions for multiresistant gram-negative bacilli in Australian hospitals: Analysis of a national survey

Despite the global expansion of extended spectrum β-lactamase-harboring Enterobacteriaceae (ESBL-E) and carbapenem-resistant Enterobacteriaceae (CRE), only limited research on the infection control management of patients with these organisms is available. We present a national survey of infection control practices amongst adult acute-care hospitals in Australia, for ESBL-E, CRE, and the emerging threat of patients with overseas health care contact. In total, 97 health services responded, representing 9% of all eligible hospitals. The proportion of hospitals that reported use of contact precautions (CP) was 96% (93 out of 97) for ESBL-E, 81% (79 out of 97) for CRE, and 72% (48 out of 67) for patients transferred from an international hospital. For ESBL-E hospitals frequently employed risk-stratification to limit the use of CP (40 out of 97; 41%). On multivariate analysis predictors of a strategy to limit use of CP for ESBL-E were government funding (odds ratio, 4.8; P = .003) and a metropolitan location (odds ratio, 3.2; P = .014); predictors of any use of CP for CRE were location in an Australian state with a specific legislation on CRE (P = .030) and the presence of a written policy on CRE (P = .011). Infection control management of multiresistant gram-negative bacilli varied considerably across the Australian hospitals surveyed. A lower rate of reported CP use for CRE than for ESBL-E was unexpected and indicates a vulnerability in some Australian hospitals. Multivariate analysis revealed various drivers influencing infection control practice in Australia.

Daptomycin for a complicated urinary tract infection with vancomycin-resistant Enterococcus faecium in a renal transplant recipient.

There is an increasing prevalence of urinary tract infection (UTI) caused by multiresistant gram-negative enteric bacilli such as extended-spectrum beta-lactamase as well as Gram-positive enterococci whose vancomycin-resistance can be as high as 25%. We report on a 68-year-old Caucasian female with a UTI caused by a vancomycin-resistant Enterococcus faecium, only tested to be susceptible to gentamycin, linezolid and daptomycin. Within a day after administration of the bactericidal daptomycin clinical and laboratory signs of infection regressed and graft function recovered. Our case suggests that daptomycin might be an effective alternative for UTI caused by vancomycin-resistant enterococci.

In Vitro Properties of BAL30072, a Novel Siderophore Sulfactam with Activity against Multiresistant Gram-Negative Bacilli

BAL30072 is a new monocyclic beta-lactam antibiotic belonging to the sulfactams. Its spectrum of activity against significant Gram-negative pathogens with beta-lactam-resistant phenotypes was evaluated and was compared with the activities of reference drugs, including aztreonam, ceftazidime, cefepime, meropenem, imipenem, and piperacillin-tazobactam. BAL30072 showed potent activity against multidrug-resistant (MDR) Pseudomonas aeruginosa and Acinetobacter sp. isolates, including many carbapenem-resistant strains. The MIC(90)s were 4 microg/ml for MDR Acinetobacter spp. and 8 microg/ml for MDR P. aeruginosa, whereas the MIC(90) of meropenem for the same sets of isolates was >32 microg/ml. BAL30072 was bactericidal against both Acinetobacter spp. and P. aeruginosa, even against strains that produced metallo-beta-lactamases that conferred resistance to all other beta-lactams tested, including aztreonam. It was also active against many species of MDR isolates of the Enterobacteriaceae family, including isolates that had a class A carbapenemase or a metallo-beta-lactamase. Unlike other monocyclic beta-lactams, BAL30072 was found to trigger the spheroplasting and lysis of Escherichia coli rather than the formation of extensive filaments. The basis for this unusual property is its inhibition of the bifunctional penicillin-binding proteins PBP 1a and PBP 1b, in addition to its high affinity for PBP 3, which is the target of monobactams, such as aztreonam.

Penetration of Colistin into Cerebrospinal Fluid

Colistin penetration into the cerebrospinal fluid (CSF) was studied in five critically ill adult patients receiving colistin methanesulfonate for infections by multiresistant gram-negative bacilli. Colistin concentrations were determined in paired serum and CSF samples, with the latter taken by lumbar puncture, with the exception of one patient with an external ventriculostomy. CSF-to-serum ratios (0.051 to 0.057) for all study patients coincided at all sampling times. The low level (5%) of penetration suggests inadequate bactericidal colistin concentrations in the CSF.

Colistin in the treatment of sepsis from multi-resistant Gram-negative bacilli in burned patients

Colistin in the treatment of sepsis from multi-resistant Gram-negative bacilli in burned patients

Characteristics of doripenem: a new broad-spectrum antibiotic

Doripenem (S-4661) is a new parenteral antibiotic from the carbapenem class; similarly to imipenem and meropenem, it has a broad-spectrum activity against Gram-positive, Gram-negative, and anaerobic bacteria. It is active against multiresistant Gram-negative bacilli such as extended-spectrum beta-lactamase-producing (ESBL) Gram-negative Enterobacteriaceae and nonfermentative Gram-negative bacilli including some strains of Pseudomonas aeruginosa that are resistant to other carbapenems. Doripenem's chemical structure is similar to that of meropenem (substitution of one sulfamoxil-aminomethyl chain for the dimethyl-carboxyl chain), and has one 1-beta-methyl chain which provides resistance to dehydropeptidase-I enzyme. The clinical trials conducted so far have focused on the treatment of severe infections such as complicated intra-abdominal infections, complicated urinary tract infections and pyelonephritis, nosocomial pneumonia, and ventilator-associated pneumonia. Given its activity profile and the results from the clinical trials, this antibiotic may be used for empirical treatment of multibacterial infections produced by potentially multiresistant Gram-negative bacilli. In 2007, the US Food and Drug Administration approved the use of doripenem for the treatment of complicated intra-abdominal infections and complicated urinary tract infections. The European Medicines Agency has approved the use of doripenem for the same indications in addition to nosocomial pneumonia regardless of whether it is ventilator-associated or not.

Aminoglucósidos y polimixinas

The emergence of multidrug-resistant strains of gram-negative bacilli during the last decade has generated renewed interest in older antimicrobials that had been relegated to a second line because of a poorer safety profile, but that are still active against these microorganisms. Once-daily administration of aminoglycosides has limited the toxicity of these agents and enabled their reintroduction into clinical practice. Recent studies have shown no additional benefits of concomitant administration of aminoglycosides with current ss-lactams, and the available evidence does not support the use of once-daily administration for all indications. The new formulations and dosages of polymyxins have also reduced the toxicity rates attributed to these agents in the past. Although more extensive studies are required to properly define their pharmacokinetics and effectiveness, the available data have shown favorable outcomes for patients with infection due to multiresistant gram-negative bacilli treated with colistin, either alone or combined with other antimicrobial agents.

Risk Factors for Infection with Extended-Spectrum and AmpC β-Lactamase-Producing Gram-Negative Rods in Renal Transplantation

Increasing prevalence of infections caused by multiresistant gram-negative enteric bacilli due to synthesis of extended-spectrum beta-lactamase (ESBL) or to desrepressed chromosomic AmpC beta-lactamase (AmpC) is a major concern in the hospitalized patient population. Renal transplant recipients are especially susceptible to these infections. A cohort observational study in a 3-year period was performed. ESBL-production was determined by phenotypic analysis based on the CLSI recommendations. A multi-variate logistic regression analysis was performed to identify independent variables associated with multi-resistant gram-negative bacilli infection. The study included 417 patients (61 double kidney-pancreas recipients). The incidence of ESBL-producing and desrepressed chromosomic AmpC beta-lactamase resistance was 11.8% (49 patients). The most frequent bacteria isolated was E. coli (35/60 isolations), followed by Klebsiella spp(12/60 isolations). Double kidney-pancreas transplantation(OR 3.5, CI95% 1.6-7.8), previous use of antibiotics(OR 2.1,CI95% 1.1-4.1), posttransplant dialysis requirement (OR 3.1, CI95% 1.5-6.4) and posttransplant urinary obstruction (OR 5.8, CI95% 2.2-14.9) were independent variables associated with these multiresistant gram-negative enteric bacilli infections. The incidence of ESBL-producing and desrepressed AmpC beta-lactamase gram-negative enteric bacilli infection in our population was high. These infections are associated with significant morbidity after renal transplantation.

Colistin treatment in patients with ICU-acquired infections caused by multiresistant Gram-negative bacteria: the renaissance of an old antibiotic

A retrospective case series study was performed in a 30-bed general intensive care unit (ICU) of a tertiary care hospital to assess the effectiveness and safety of colistin in 43 critically ill patients with ICU-acquired infections caused by multiresistant Gram-negative bacteria. Various ICU-acquired infections, mainly pneumonia and bacteraemia caused by multiresistant strains of Pseudomonas aeruginosa and/or Acinetobacter baumannii, were treated with colistin. Good clinical response (cure or improvement) was noted in 74.4% of patients. Deterioration of renal function occurred in 18.6% of patients during colistin therapy. Nephrotoxicity was elevated significantly in those patients with a history of renal failure (62.5%). All-cause mortality amounted to 27.9%. In this group of critically ill patients, an age of >50 years (OR, 5.4; 95% CI 1.3-24.9) and acute renal failure (OR, 8.2; 95% CI 2.9-23.8) were independent predictors of mortality. Colistin should be considered as a treatment option in critically ill patients with infection caused by multiresistant Gram-negative bacilli.