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The epidemiology of bacterial infections during HIV (human immune deficiency virus) infection changed after the introduction of HAART (highly active antiretroviral therapy) and of the prophylaxis programmes addressing the associated infections, which led to an increased prevalence of some of them. Despite the relatively low incidence, the gram-negative bacilli (GNB) infections must be suspected in the case of bacterial complications in these patients, considering the severe potential of respiratory and systemic infections caused, and also the variable susceptibility to antibiotics. The study targets the peculiar etiologic and clinical aspects of GNB infections in seropositive patients vs. seronegative ones, the characterization of germs from the antibiotics sensitivity point of view and the connection with the severity of the immune suppression. The data are analyzed and the results are presented in a comparative manner with those obtained from non-infected HIV patients. The retrospective study supports the implication of deep immune suppression in causing the severe GNB infections, the role of HAART in preventing the respiratory complications caused by these germ and also the recommendation of the antibiotherapy uninfluenced by the seropositivity status. [ABSTRACT FROM AUTHOR]

Background: Gram-negative bacilli are the most common bacteria causing nosocomial bloodstream infections (NBSIs) in Latin American countries. Methods: The antibiotic resistance profiles of Gram-negative bacilli isolated from blood cultures in pediatric patients with NBSIs over a 3-year period in a tertiary care pediatric hospital in Mexico City were determined using the VITEK-2 system. Sixteen antibiotics were tested to ascertain the resistance rate and the minimum inhibitory concentration using the Clinical Laboratory Standards Institute (CLSI) broth micro-dilution method as a reference. Results: A total of 931 isolates were recovered from 847 clinically significant episodes of NBSI. Of these, 477 (51.2%) were caused by Gram-negative bacilli. The most common Gram-negative bacilli found were Klebsiella pneumoniae (30.4%), Escherichia coli (18.9%), Enterobacter cloacae (15.1%), Pseudomonas aeruginosa (9.9%), and Acinetobacter baumannii (4.6%). More than 45 and 60% of the K. pneumoniae and E. coli isolates, respectively, were resistant to cephalosporins, and 64% of the E. coli isolates were resistant to fluoroquinolones. A. baumannii exhibited low rates of resistance to antibiotics tested. In the E. cloacae and P. aeruginosa isolates, no rates of resistance higher than 38% were observed. Conclusions: In this study, we found that the proportion of NBSIs due to antibiotic-resistant organisms is increasing in a tertiary care pediatric hospital of Mexico. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Globally, antimicrobial resistance is alarming concern especially in commonly reported disease entities like respiratory tract infection, enteric fever and infections associated with gram-negative bacilli (GNB). Rational use of antimicrobial drugs reported significant decrease in bacterial burden and may also reduce the risk of disease progression. However, at times in particular indication, certain patient and pathogen factor limits the selection and use of specific antibiotic therapy while in some case, due to presence of additional risk factor, aggressive therapy is required to achieve clinical reemission and prevent complications. Delay in start of suitable antibiotic therapy is another imperative factor for treatment failure and rise of drug resistance. With rapidly increasing antibiotic resistance and decline in new antibiotic drug development, the toughest challenge remains to maintain and preserve the efficacy of currently available antibiotics. Therefore, the best rational approach to fight these infections is to 'hit early and hit hard' and kills drug-susceptible bacteria before they become resistant. The preferred approach is to deploy two antibiotics that produce a stronger effect in combination than if either drug were used alone. Various society guidelines in particular indications also justify and recommend the use of combination of antimicrobial therapy. Combination therapies have distinct advantage over monotherapy in terms of broad coverage, synergistic effect and prevention of emergence of drug resistance. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to demonstrate the changing epidemiology of infecting microorganisms and their long-term resistance profiles and to describe the microbiological point of view in anti-infective management of intensive care unit (ICU) patients. Methodology: A total of 5,690 isolates of Gram-negative bacilli were included in this study. Antibiotic susceptibility was tested using the disk diffusion method and Vitek 2 system. Chi-square tests were used for hypothesis testing. Results: The most frequently isolated organisms were A. baumannii (37.3%), P. aeruginosa (30.3%), Enterobacter spp. (10.4%), E. coli (10.4%), and Klebsiella spp. (8.9%). A. baumannii was the most frequently isolated organism from the respiratory tract (43.4%); the susceptibility rates for imipenem and meropenem decreased to 7% and 6% (p < 0.0001), respectively. The percentage of multidrug-resistant (MDR) A. baumannii isolates continuously increased from 18.7% in 2004 to 69% in 2011 (p < 0.0001), whereas MDR P. aeruginosa isolates increased from 1.5% to 22% (p < 0.0001). Carbapenem-resistant Klebsiella isolates emerged in 2010 and increased to 20% in the next year. The rates of ESBL-producing Enterobacteriaceae in the ICU was very high in 2011 -- 50% for E. coli and 80% for Klebsiella strains. Conclusion: The most common isolated Gram-negative bacillus in our study was A. baumannii and that the prevalence of MDR isolates has increased markedly over. Accordingly, the comparison of antibiotic resistance of other pathogens in 2004 and 2011 displayed an increasing trend. These data imply the urgent need for new and effective strategies in our hospital and in the region. [ABSTRACT FROM AUTHOR]

Skin and soft tissue infections (SSTI) are an important cause of morbidity and mortality in patients with cirrhosis. This prospective study aimed to analyze the clinical profile and factors affecting outcome of SSTIs in cirrhotics. All cirrhotics hospitalized between September 2007 and August 2010 were included. Frequency, site, extent, and type of SSTI were noted. Of 1,395 cirrhotics, 19.4 % ( n = 271) had bacterial infections, out of which 32.8 % (89/271) had SSTI. Alcohol was the predominant etiological factor for cirrhosis; 95.2 % belonged to Child class B/C, and 67 % gave history of barefoot walking. The most common site of SSTI was the lower limbs (87.1 %), cellulitis was the most common type (61.2 %), and gram-negative bacilli (GNB) is the most common organism (86.7 %). Mortality rate was 23.5 %. Serum creatinine and model for end-stage liver disease (MELD) score were independent predictors of mortality. SSTIs in cirrhotics were common and mostly involved the lower limbs. Cellulitis was the most common type, and GNB was the most common organism. Serum creatinine and MELD score were independent predictors of mortality. [ABSTRACT FROM AUTHOR]

Background: Non-fermenting gram-negative bacilli (NFGNB) are an emerging problem in neonatal sepsis. A major concern is multi-drug resistance which severely limits treatment options. Aims and Objectives: A retrospective observational study was conducted to analyse the role of non-fermenters in neonatal sepsis over a 4-year period, the factors leading to this trend and the pattern of antibiotic resistance. Methods: Demographic and clinical data were collected for all neonates with blood culture-positive sepsis during the study period, January 2007 to December 2010. Results: Blood cultures were positive in 186 (13%) of 1402 neonates, in 44 (32·1%) of whom the cause was NFGNB. Acinetobacter spp was the most common organism (n = 30). Infection by NFGNB showed a steady increase (P<0·0001), and was fairly evenly distributed between early- and late-onset sepsis. The infection rate was significantly higher in inborn neonates (P = 0·04) and those delivered vaginally (P = 0·002). Multi-drug resistance (MDR) occurred in 50% and carbapenem resistance in 30% of Acinetobacter spp isolates. In five cases there was panresistance of Acinetobacter spp to all antibiotics tested. Conclusion: The trend of increasing numbers of cases of NFGNB in neonatal sepsis compounded by MDR is of great concern. It is necessary to administer antibiotics judiciously, strengthen surveillance and laboratory services in neonatal intensive care units, and re-evaluate treatment guidelines for management of infection by these organisms. [ABSTRACT FROM AUTHOR]

Objective: The clinical and laboratory characteristics of non-cephalosporin-susceptible (non-CS) glucose non-fermentative Gram-negative (G(-)) infections in adults with postneurosurgical meningitis are rarely examined solely in the literature. Methods: The data of 28 post-neurosurgical adults meningitis with glucose non-fermentative G(-) infections, collected during a study period of 5 years (2006-2010), were reviewed. The clinical and laboratory data between the non-cephalosporin-susceptible groups and the cephalosporin-susceptible groups were compared. Results: A total of 30 G(-) strains were collected from the 28 enrolled cases. Among the implicated-glucose non-fermentative G(-) strains, 18 strains, belonging to 17 cases, were non-CS. Among the 18 non-cephalosporin-susceptible strains, Acinetobacter spp. (39%, 7/18) was the most common, followed by Pseudomonas spp. (22%, 4/18), Stenotrophomonas maltophilia (22%, 4/18) and Elizabethkingia meningoseptica (11%, 2/18). With a comparative analysis, there were no significant difference between the non-cephalosporin-susceptible and cephalosporin-susceptible glucose non-fermentative G(-) groups. The clinical and laboratory data were also of no statistical significance between the fatal (n = 4) and non-fatal (n = 13) non-cephalosporin-susceptible groups. Conclusion: Sixty percent (18/30) of implicated glucose non-fermentative G(-) strains of post-NS meningitis in adults are non-cephalosporin-susceptible. Among the non-cephalosporin-susceptible glucose non-fermentative G(-) strains, Acinetobacter spp., Pseudomonas spp., S. maltophilia and E. meningoseptica are the commonly implicated pathogens, and their emergence in this specific group of meningitis has caused a therapeutic dilemma. The clinical manifestations of non-cephalosporin-susceptible glucose non-fermentative G(-) meningitis were not unique; therefore, only bacterial culture and antimicrobial susceptibility test are the methods for identification confirmation. [ABSTRACT FROM AUTHOR]

Background: Increasing multidrug resistance in gram-negative bacilli (GNB) infections poses a serious threat to public health. Few studies have analyzed co-resistance rates, defined as an antimicrobial susceptibility profile in a subset already resistant to one specific antibiotic. The epidemiologic and clinical utility of determining co-resistance rates are analyzed and discussed. Methods: A 10-year retrospective study from 2002–2011 of bloodstream infections with GNB were analyzed from three hospitals in Greater Vancouver, BC, Canada. Descriptive statistics were calculated for antimicrobial resistance and co-resistance. Statistical analysis further described temporal trends of antimicrobial resistance, correlations of resistance between combinations of antimicrobials, and temporal trends in co-resistance patterns. Results: The total number of unique blood stream isolates of GNB was 3280. Increasing resistance to individual antimicrobials was observed for E. coli, K. pneumoniae, K. oxytoca, E. cloacae, and P. aeruginosa. Ciprofloxacin resistance in E. coli peaked in 2006 at 40% and subsequently stabilized at 29% in 2011, corresponding to decreasing ciprofloxacin usage after 2007, as assessed by defined daily dose utilization data. High co-resistance rates were observed for ceftriaxone-resistant E. coli with ciprofloxacin (73%), ceftriaxone-resistant K. pneumoniae with trimethoprim-sulfamethoxazole (83%), ciprofloxacin-resistant E. cloacae with ticarcillin-clavulanate (91%), and piperacillin-tazobactam-resistant P. aeruginosa with ceftazidime (83%). Conclusions: Increasing antimicrobial resistance was demonstrated over the study period, which may partially be associated with antimicrobial consumption. The study of co-resistance rates in multidrug resistant GNB provides insight into the epidemiology of resistance acquisition, and may be used as a clinical tool to aid prescribing empiric antimicrobial therapy. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine the level of antibiotic resistance patterns and distribution of heavy metal resistance of bacterial isolates from aquatic animals ( Lissotriton vulgaris, Pelophylax ridibundus, Emys orbicularis, Mauremys rivulata, and Natrix natrix) in Turkey (Kavak Delta). A total of 153 bacteria have been successfully isolated from cloaca and oral samples of the aquatic amphibians and reptilians which were found, namely, Aeromonas sp. ( n = 29), Plesiomonas sp. ( n = 7), Vibrio sp. ( n = 12), Citrobacter sp. ( n = 12), Enterobacter sp. ( n = 11), Escherichia sp. ( n = 22), Klebsiella sp. ( n = 22), Edwardsiella sp. ( n = 6), Hafnia sp. ( n = 1), Proteus sp. ( n = 19), Providencia sp. ( n = 8), and Pseudomonas sp. ( n = 4). In terms of antibiotic and heavy metal susceptibility testing, each isolate was tested against 12 antibiotics and 4 metals. There was a high incidence of resistance to cefoxitin (46.40 %), ampicillin (44.44 %), erythromycin (35.29 %), and a low incidence of resistance to gentamicin (6.53 %), kanamycin (8.49 %), chloramphenicol (9.15 %), and cefotaxime (10.45 %). The multiple antibiotic resistance index of each bacterial species indicated that bacteria from raised amphibians and reptiles have been exposed to tested antibiotics, with results ranging from 0 to 0.58. Most isolates showed tolerance to different concentrations of heavy metals, and minimal inhibition concentrations ranged from100 to >3,200 μg/mL. According to these results, a significant occurrence of bacteria in the internal organs of reptiles and amphibians, with a high incidence of resistance against antibiotics and heavy metals, may risk aquatic animals and the public health. These data appoint the importance of epidemiological surveillance and microbiological monitoring and reinforce the need to implement environment protection programs for amphibian and reptile species. [ABSTRACT FROM AUTHOR]

Over the last few decades, β-lactams are the most widely used and favored antimicrobials worldwide, because of their efficacy, broad spectra and low toxicity. They inhibit the bacterial penicillin-binding proteins (PBPs), which are the enzymes that catalyze the final cross-linking of the bacterial cell wall polymer, peptidoglycan. However, due to heavy use of β-lactams antibiotics, bacteria developed various mechanism of resistance. Modification or substitution of the PBPs is important mechanism in gram-positive cocci, while production of β-lactamases is main cause of resistance among gram-negative bacilli. Mostly plasmid harbors the resistance gene and therefore, is crucial in disseminating resistance into previously susceptible species. Throughout the 1960s and 1970s there was a relentless rise in reports of resistance to β-lactams as a consequence of the selection of bacteria that produce β-lactamases. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Enterobacterales (CRE) possessing various carbapenemases, particularly the OXA-48 group, are now rapidly spreading and becoming a major public health concern worldwide. Phenotypic detection of OXA-48-like carbapenemases is still suboptimal due to their weak carbapenemase activity, whereas highly sensitive and specific polymerase chain reaction (PCR)-based methods take at least 3-4 h. We, therefore, developed a recombinase polymerase amplification (RPA) combined with lateral flow (LF) strip assay for the rapid detection of bla OXA-48-like -carrying Enterobacterales isolates and 70 Gram-negative bacilli isolates containing other bla OXA-48-like -carrying Enterobacterales isolates and 70 Gram-negative bacilli isolates containing other bla genes were subjected to the RPA method performed under isothermal conditions at 37 °C within 10 min and visually inspected by LF strip within 5 min. The RPA-LF assay provided 100% sensitivity (95% confidence interval, 92.6-100%) and 100% specificity (93.5-100%) for detecting bla OXA-48-like genes from bacterial colonies. Its detection limit was 100 times less than that of the PCR method. This assay is rapid, easy to perform, and provides excellent performance without any special equipment. It may be applied for directly identifying the bla OXA-48-like genes in Enterobacterales obtained from blood culture. Rapid identification of carbapenemase types is essential for selecting appropriate antimicrobial options, particularly the β-lactams combined with novel β-lactamase inhibitors.

Carbapenem resistance (CR) is an emerging health issue. Epidemiological surveys on carbapenem-resistant Gram-negative bacilli (CR-GNB) in Lebanon remain scarce. In this study, we determined the prevalence of CR-GNB isolated between 2015 to 2019 in three hospitals in northern Lebanon: 311 CR- Enterobacterales (out of 11210; 2.8%), 155 CR- Pseudomonas (out of 1034; 15%) and 106 CR- Acinetobacter (out of 184; 57.6%) were identified. CR mechanisms were determined for 146 randomly chosen isolates: the Carba NP test revealed an enzymatic resistance to carbapenems in 109 isolates (out of 146, 74.7%). Produced carbapenemases were evaluated by the NG-Test Carba5, NG-Test OXA-23 immunochromatographic assays and PCR. Carbapenemase-producing (CP) Enterobacterales expressed bla OXA-48 -like, bla NDM -like and bla VIM -like genes and CP- Pseudomonas expressed bla IMP -like and bla VIM -like genes, whereas CP- Acinetobacter expressed bla OXA-23 -like genes. The NG-Test Carba5 results were confirmed by PCR sequencing and revealed several variants, such as NDM-19, VIM-62 and OXA-162, never described so far in Lebanon. Isolates with discordant results were sequenced by WGS and highlighted novel variants of the natural oxacillinases of Pseudomonas aeruginosa : bla OXA-50 -like genes. Their role in carbapenem resistance should be further studied. Overall, our findings highlight an alarming situation and encourage health care centers to establish performant registration systems that could help in limiting resistance spread.

Prosthetic joint infections (PJIs) are typically caused by microorganisms that grow in biofilms. Traditional antimicrobial susceptibility tests are based on the study of planktonic bacteria that might lead to missing the biofilm behavior and to a treatment failure. This study was designed to analyze the antimicrobial susceptibility of clinical Gram-negative bacilli (GNB) isolates from PJIs in planktonic and sessile states and the possible relationship between antimicrobial resistance and biofilm formation. A total of 46 clinical isolates from patients with PJIs (mainly hip and knee prostheses) plus three GNB ATCC isolates were studied. The Minimal Inhibitory Concentration (MIC), minimal bactericidal concentration (MBC), minimal biofilm inhibitory concentration (MBIC), and minimal biofilm eradication concentration (MBEC) were assessed using a previously published methodology. Almost all of the GNB clinical isolates tested were biofilm forming. Pseudomonas aeruginosa was the largest biofilm-forming species. A comparison of MBIC 90 versus MIC 90 shows an increase higher than 1- to -2-fold dilutions in most antimicrobials studied, and MBEC90 was significantly higher than MIC90, becoming resistant to all the antimicrobial drugs tested. Higher biofilm production values were obtained in antibiotic-susceptible Escherichia coli in comparison to their resistant counterparts. However, regarding the relationships between antimicrobial resistance and biofilm formation, our analysis showed that each strain differed. A high antimicrobial resistance rate was found among the GNB studied. Moreover, almost all bacterial isolates were in vitro biofilm formers. Although there was no significant association between biofilm and antibiotic resistance, multidrug-resistant isolates were found to be greater biofilm formers than non-multidrug-resistant isolates. IMPORTANCE This study is the first one to analyze a high number of isolates of Gram-negative bacilli that are the cause of prosthetic joint infection. The analysis includes biofilm development and antimicrobial susceptibility testing of both planktonic and sessile bacteria. The obtained results support the clinical knowledge about the treatment of these bacteria when biofilms are involved.

Background: Gram-negative bacteremia (GNB) as a manifestation of cardiovascular implantable electronic device (CIED) infection is uncommon. Moreover, echocardiography may be nonspecific in its ability to differentiate whether CIED lead masses are infected. We aimed to determine the rate of CIED infection in the setting of GNB., Methods: All patients with CIED who were hospitalized with GNB during 2012-2019 at Mayo Clinic were investigated. The definition of CIED infection was based on criteria recommended by the 2019 European Heart Rhythm Association document., Results: A total of 126 patients with CIED developed GNB. None of them had signs of pocket infection. Twenty (15.9%) patients underwent transesophageal echocardiography. Overall, 4 (3%) patients had definite CIED infection. None of them underwent CIED extraction; 3 died within 12 weeks and 1 received long-term antibiotic suppression. Ten (8%) patients had possible CIED infection; despite no CIED extraction, no patient had relapsing GNB. We observed a higher rate of CIED infection in patients with Serratia marcescens bacteremia as compared to that in patients with other GNB., Conclusions: The rate of CIED infection following GNB was relatively low. However, accurate classification of CIED infection among patients presenting with GNB remains challenging, in part, due to a case definition of CIED infection that is characterized by a low pretest probability in the setting of GNB. Prospective, multicenter studies are needed to determine accurate identification of CIED infection among GNB, so that only patients with true infection undergo device removal., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The burden of disease due to bacterial meningitis is shifting toward older adults. Clinicians should maintain a high level of suspicion of meningitis in older adults, since they may present without classic signs and symptoms. Clinicians should remember that more older patients are at risk of healthcare-associated meningitis and may be at risk of more resistant organisms. A lumbar puncture should be performed as quickly as possible. If a CT scan is required before the lumbar puncture, blood cultures should be drawn and appropriate empiric antibiotics should be started before sending the patient to the CT scanner. Empiric antibiotics should be chosen based on patient history, review of patient's known illnesses and risk factors, results of CSF Gram stain, and local institution antibiotic resistance patterns. Clinicians should remember that Streptococcus pneumoniae may be resistant to penicillin and cephalosporins, so vancomycin is usually also administered until the bacterial resistance pattern is known. Adjunctive dexamethasone may be started before or at the time of antibiotic therapy based on risk versus benefit analysis, and may be discontinued if patient is found to not have Streptococcus pneumoniae meningitis. [ABSTRACT FROM AUTHOR]

Abstract: Carbapenems are increasingly needed to treat infections caused by drug-resistant gram-negative bacilli (GNB), but carbapenem resistance is increasing. We evaluated the activity of doripenem by broth microdilution against 96 extensively drug-resistant (XDR) Acinetobacter baumannii and Klebsiella pneumoniae isolates from patients with hospital-associated infections. All isolates were non-susceptible to doripenem, but ≥1 doripenem combination demonstrated synergy (fractional inhibitory concentration index: ≤0.5 for 2 agents, ≤0.75 for 3 agents) against 7 (15%) A. baumannii and 23 (48%) K. pneumoniae isolates; doripenem with rifampin and/or polymyxin B were most active. As doripenem has unique potential for use in prolonged infusions, suggested pharmacodynamic (PD) breakpoints range from 2–8 μg/mL; synergistic activity was found for higher proportions of XDR-GNB at higher PD breakpoints with doripenem with amikacin or with rifampin. The clinical utility of these observations requires further study, as treatment options for XDR-GNB infections are limited. [Copyright &y& Elsevier]

Infections caused by antibiotic-resistant bacteria, especially the “ESKAPE” pathogens, continue to increase in frequency and cause significant morbidity and mortality. New antimicrobial agents are greatly needed to treat infections caused by gram-negative bacilli (GNB) resistant to currently available agents. The Infectious Diseases Society of America (IDSA) continues to propose legislative, regulatory, and funding solutions to this continuing crisis. The current report updates the status of development and approval of systemic antibiotics in the United States as of early 2013. Only 2 new antibiotics have been approved since IDSA's 2009 pipeline status report, and the number of new antibiotics annually approved for marketing in the United States continues to decline. We identified 7 drugs in clinical development for treatment of infections caused by resistant GNB. None of these agents was included in our 2009 list of antibacterial compounds in phase 2 or later development, but unfortunately none addresses the entire spectrum of clinically relevant GNB resistance. Our survey demonstrates some progress in development of new antibacterial drugs that target infections caused by resistant GNB, but progress remains alarmingly elusive. IDSA stresses our conviction that the antibiotic pipeline problem can be solved by the collaboration of global leaders to develop creative incentives that will stimulate new antibacterial research and development. Our aim is the creation of a sustainable global antibacterial drug research and development enterprise with the power in the short term to develop 10 new, safe, and efficacious systemically administered antibiotics by 2020 as called for in IDSA's “10 × '20 Initiative.” [ABSTRACT FROM AUTHOR]

Summary: Background: Pressure ulcers (PUs) represent a major problem for hospitalized patients, health professionals and society. Aim: To evaluate the impact of in-hospital PUs as a reservoir of multidrug-resistant organisms (MDROs), risk factor for bacteraemia and predictor of poor prognosis. Methods: A prospective cohort study of patients with stage II or greater PUs hospitalized in a tertiary acute care university teaching hospital for more than 48 h was performed to evaluate colonization/infection by potential and/or multi-resistant hospital pathogens from April to December 2005 and from August 2009 to April 2010. Findings: A total of 145 patients with stage II or greater PUs were included. Of these, 76.5% (111/145) had PUs colonized and/or infected with either S. aureus (20.7%), Gram-negative bacilli (32.5%), or both (46.8%) and most were MDROs (64.8%). Bacteraemia was detected in 50.5% (56/111) of the patients. The ulcers were considered to be the probable source of bacteraemia in 53.6% (30/56) of the episodes. Prior administration of antibiotics (P = 0.04) and infected wound (P < 0.001) were the variables independently associated with bloodstream infection as well as associated with a higher 30-day mortality rate; risk factors for the latter included hospitalization in ICU (P = 0.03) and mechanical ventilation use (P = 0.05). Conclusions: Our results suggest that besides being a major reservoir of MDROs, patients with PUs constitute a high-risk population for bacteraemia with a poor outcome. Broad-spectrum antibiotics and infected wound were independent factors predisposing patients to both bacteraemia and death. [ABSTRACT FROM AUTHOR]

Complicated urinary tract infection is a challenging infection, since cure is difficult and either persistence or recurrence is common. The challenge is frequently increased because complicated urinary tract infection is often caused by gram-negative bacilli resistant to multiple antimicrobial drugs. In this review, we approach the therapy of complicated urinary tract infection with an emphasis on those caused by antimicrobial drug-resistant gram-negative uropathogens. [ABSTRACT FROM AUTHOR]

The success of modern anticancer treatment is a composite function of enhanced efficacy of surgical, radiation and systemic treatment strategies and of our collective clinical abilities in supporting patients through the perils of their cancer journeys. Despite the widespread availability of antibacterial therapies, the threat of community- or healthcare facility-acquired bacterial infection remains a constant risk to patients during this journey. The rising prevalence of colonization by multidrug-resistant (MDR) bacteria in the population, acquired through exposure from endemic environments, antimicrobial stewardship and infection prevention and control strategies notwithstanding, increases the likelihood that such organisms may be the cause of cancer treatment-related infection and the likelihood of antibacterial treatment failure. The high mortality associated with invasive MDR bacterial infection increases the likelihood that many patients may not survive long enough to reap the benefits of enhanced anticancer treatments, thus threatening the societal investment in the cancer journey. Since cancer care providers arguably no longer have, and are unlikely to have in the foreseeable future, the antibacterial tools to reliably rescue patients from harm's way, the difficult ethical debate over the risks and benefits of anticancer treatments must now be reopened. [ABSTRACT FROM PUBLISHER]

Abstract: The Del Pozo and Patel (DPP) algorithm permits to identify suitable candidates for debridement and implant retention (DR) in prosthetic joint infections (PJI), but does not include gram-negative bacilli (GNB) as a risk factor of worst outcome. We conducted a retrospective study to validate the DPP algorithm and propose a simplified algorithm including GNB PJI. From 2002 to 2009, 73 PJI underwent surgery; 55% were chosen according to PDD algorithm. Non-adherence increased the risk of treatment failure (HR = 4.2). Performing DR in the presence of GNB PJI and performing DR in a joint prosthesis implanted for >3 months without hematogenous infection were independent risk factors. Our simplified algorithm, based on these 2 criteria, showed comparable performance to the DPP algorithm but increased eligibility for DR by a 2.4 fold. [Copyright &y& Elsevier]

Purpose: To examine the status and clinical outcome of de-escalating antimicrobial therapy for bacteraemia due to hospital-acquired, Gram-negative bacilli that are difficult to treat. Methods: Among 1,610 patients presenting with positive blood cultures collected at our medical centre over a 6-year period, 133 were infected with Serratia, Pseudomonas, Acinetobacter, Citrobacter or Enterobacter sp. (SPACES). We examined the appropriateness of an empiric initial administration of antimicrobials based on in vitro sensitivity, and the success and outcomes of a pathogen-directed de-escalation of therapy. The treatment was considered to be successfully de-escalated when the antimicrobial spectrum was narrowed according to a spectrum ranking or when ≥2 antimicrobials prescribed initially were lowered to one agent. Outcome measures included persistent, recurrent and metastatic infections, infection-related deaths and cost of antimicrobials. Results: The treatment was initially appropriate in 79 of 133 patients (59 %), of whom 49 (62 %) were candidates for and 28 (57 %) underwent treatment de-escalation. No treatment failure was observed among these 28 patients, while 2 of 11 patients (18 %) whose treatment was not de-escalated died ( p = 0.13). The median cost of antimicrobials was €250/patient lower in the de-escalated than in the non-de-escalated group ( p < 0.001). Conclusions: Antimicrobial therapy for bacteraemia due to hard-to-treat SPACES was de-escalated in 57 % of candidates, based on the in vitro sensitivity, with no deaths and significantly lower costs of antimicrobial therapy. [ABSTRACT FROM AUTHOR]

Purpose: Metallo β-lactamases (MβL) production is a worldwide problem, particularly in gram-negative bacteria. As scanty data is available on the prevalence of MBL, the present study is being undertaken to determine the prevalence, antibacterial sensitivity patterns, and molecular characterization of MβL associated resistant genes in gram-negative bacteria isolated from ocular infections., Material and Methods: At a tertiary eye care center in south India, 359 gram-negative pathogens, 200 isolates from eye infections, and 159 isolates from normal flora of the eye were studied. A gold standard microbiology method was used to identify the isolates. An antibiotic double disc synergy test and a combination disc test were used to detect MβL production. Multiplex PCR was used to investigate the molecular characteristics of the MβL encoding genes bla VIM , bla IMP , and bla NDM ., Results: Of the 359 gram-negative bacterial pathogens, Pseudomonas aeruginosa 108 (30.1%) and Enterobacter agglomerans 46 (12.8%) were commonly isolated. High prevalence of P. aeruginosa 81% (17 strains) was detected as an MβL producer and it shows 100% resistance to 2nd and 3rd generation cephalosporins and meropenem. Multiplex PCR detected only the bla VIM gene in 56 (28%) of various eye infections and 27 (17%) of normal flora of the gram-negative bacteria (GNB). The bla VIM gene is detected predominantly in 51.8% of keratitis and 21.4% of postoperative endophthalmitis. High prevalence of the gene was detected in P. aeruginosa 42.9% (24 of 56) and Alcaligens denitrificans 10.7% (6 of 56) from eye infections. Whereas, in the control group, P. aeruginosa and E. coli each had 14.8% (4 of 27) that were shown positive., Conclusion: The emerging MβLs mediated resistance among P. aeruginosa is a challenging task for ophthalmologists, especially in patients with endophthalmitis and bacterial keratitis. This local knowledge will aid in advising appropriate antibiotic use and avoiding unnecessary antibiotic prescriptions, which are highly warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rameshkumar, Dhandapani, Lalitha, Rajapandian, Palanivel, Thangavelu, Alyousef, Albalawi, Alam, Zubair, Saleh, Alatawi and Husain.)

Purpose: The value of follow-up blood culture (FUBC) in Gram-negative bacteremia (GNB) management is controversial. We evaluated bedside risk predictors and their probabilities of yielding positive FUBCs in GNB., Methods: All adult patients with GNB in a 2700-bed tertiary center were retrospectively enrolled between January 2019 and December 2019. Only one initial GNB episode was included per patient. Positive FUBC was defined as isolation of the same organism in blood culture 48-72 h after the initial blood culture., Results: A total of 2216 patients with GNB were identified, of whom 34.4% underwent FUBC. Of the 645 patients with FUBCs analyzed in the study, 89 (13.8%) had positive FUBCs. In multivariate analysis, hemodialysis [adjusted odds ratio (aOR), 2.6], fever on the day of FUBCs (aOR 3.6), intravascular device (aOR 2.4), no use of in vitro active antibiotic within 24 h (aOR 2.5), non-fermenting bacteria (aOR 4.7), and multidrug resistance (aOR 5.4) were independent risk factors for positive FUBCs. If microbiological results were excluded in multivariate analysis, hemodialysis, immunosuppressive treatment, fever on the day of FUBCs, and intravascular device were independent bedside risk predictors for positive FUBCs. The yield of FUBCs increased from 3.0% (95% CI 1.0-7.0) to 63.6% (95% CI 25.6-100) as the number of bedside risk predictors increased from 0 to 4. In addition, positive FUBCs were significantly associated with 30 day mortality., Conclusions: FUBCs may not need to be routinely used for patients with GNB bacteremia, and bedside risk predictors could be helpful in identifying patients for whom FUBC is likely to be useful., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

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., (Copyright © 2022. Published by Elsevier España, S.L.U.)

Objectives: Antimicrobial resistance is one of the top 10 global public-health threats. Especially high rates of resistance have been reported for isolates from ICU patients, requiring expanded treatment options in this setting. We evaluated the activity of ceftolozane/tazobactam and comparators against Gram-negative isolates collected from patients with lower respiratory tract infections (LRTIs) in ICUs in seven Asian countries., Methods: In 2017-2019, up to 100 consecutive, aerobic Gram-negative LRTI isolates were collected per year at each of 37 hospitals. MICs were determined using the Clinical and Laboratory Standards Institute reference broth microdilution method., Results: Overall, ceftolozane/tazobactam was active against 72% of 1408 Enterobacterales and 86% of 761 Pseudomonas aeruginosa isolates. Susceptibility to the non-carbapenem β-lactam comparators, including piperacillin/tazobactam, was 52-67% among Enterobacterales isolates, and the activity of all β-lactam comparators, including meropenem, was 57-70% among P. aeruginosa. Ceftolozane/tazobactam maintained activity against 61% of meropenem-nonsusceptible and 64% of piperacillin/tazobactam-nonsusceptible P. aeruginosa. At the country-level, ceftolozane/tazobactam activity ranged from >90% against Enterobacterales from Hong Kong and South Korea to <64% in Thailand and Vietnam, and from >90% against P. aeruginosa from South Korea, Malaysia, Philippines and Taiwan to <75% in Thailand and Vietnam. Correspondingly, the proportions of carbapenemase-positive isolates among Enterobacterales and P. aeruginosa isolates were highest in Thailand and Vietnam., Conclusion: Ceftolozane/tazobactam provides a potential treatment option for ICU patients in Asia, which is especially important considering the reduced activity of commonly used β-lactams against the studied ICU isolates. Knowledge of local resistance patterns should inform empirical therapy decision-making., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Carbapenemase-producing Enterobacterales (CPE) pose one of the most serious antimicrobial resistance threats to public health worldwide. The outcome of CPE infection differs depending on the resistance mechanism. Therefore, rapid detection of CPE infection is essential for optimizing patient management. The carbapenem inactivation method (CIM) and modified CIM (mCIM) are standard methods for detecting CPE, but they usually require 24 h to generate results. Recently, an immunochromatographic assay, NG-Test CARBA 5, has become commercially available. It detects the five most common carbapenemase producers (KPC, IMP, NDM, VIM, and OXA-48) rapidly and accurately. We aimed to evaluate the diagnostic accuracy of NG-Test CARBA 5 for detecting carbapenemase-producing Gram-negative bacilli (CPGNB). We used 116 carbapenemase-producing strains and 48 non-carbapenemase-producing strains. Of the 116 carbapenemase-producing strains, 107 harboured genes for at least one of the five most common carbapenemases, KPC, IMP, NDM, VIM, and OXA-48-like. Forty-eight non-carbapenemase-producing strains, including carbapenem-resistant Enterobacterales , harboured genes for extended-spectrum β-lactamases (CTX-M groups [ n =25] and SHV groups [ n =2]) or plasmid-mediated AmpC β-lactamases (DHA [ n =3], CMY-2 [ n =2], and CFE-1 [ n =1]). Antimicrobial susceptibility was tested using the agar dilution method, according to the Clinical and Laboratory Standards Institute guidelines. Of the 116 carbapenemase-producing strains, 79 were resistant to at least meropenem or imipenem. The sensitivity and specificity of the NG-Test CARBA 5 for the strains were 99.1 % (106 strains positive for 107 strains of the five most common carbapenemase producers) and 100 % (60 strains negative for other types of CPGNB [ n =10] and non-CPGNB strains [ n =48]), respectively. The carbapenemase-producing strain with a false-negative result produced IMP-66. The NG-Test CARBA 5 had high sensitivity and specificity for detecting carbapenemase-producing strains.

Purpose: Incidence of carbapenem-resistant Gram-negative infections has risen alarmingly all across the globe, both in developed and developing countries alike. The purpose of this study was to assess whether challenges of life-threatening infections with very high resistance pattern can be successfully addressed by a modified approach., Methods: This is a retrospective study of 26 patients with osteoarticular and soft tissue infections with carbapenem-resistant Gram-negative bacilli treated between 2001 and 2017 with at least two year follow-up after stopping antibiotics. All were treated by a multispecialty team approach with primary aim of "source control at the earliest and avoiding recurrence at all cost". The protocol involved opting for early compromises especially in at "risk individuals", such as resorting to early amputations, especially if salvage meant multiple bony and soft tissue reconstructive procedures, explanation of prosthesis than staged revision, avoiding internal fixations, opting for shortest possible time in external fixators with reshaping and telescoping bone ends to get bony stability and increase surface area even if it meant compromising length., Results: There were five amputations, two excision arthroplasty of hip, many minor but acceptable malunions and shortening. However, lives of 24/26 patients could be salvaged, much better than most of the published data. The two patients who died had peri-prosthetic joint infection after total hip arthroplasty and presented very late in sepsis and died within days of explantation. Infection remission could be achieved in remaining patients., Conclusion: These "risk to life" cases can be successfully treated by lowering the aims and expectations from "excellent function to salvage of life and infection remission". Therein lies the "success" in these complex high-risk cases., (© 2022. The Author(s) under exclusive licence to SICOT aisbl.)

A survey of 1431 gram-negative bacilli from June 2001 to September 2005 were obtained from the faeces of 920 HIV/AIDS patients attending some Clinics and Hospitals in Benin City, Nigeria, were screened for quinolones resistance gene. The HIV/AIDS patients CD4 cells range was ≤14/mm3 ≥800/mm3 of blood. Out of the 1431 isolates, 343 (23.9%) were resistance to quinolones with a MIC ≥4μg/ml for norfloxacin, ciprofloxacin and pefloxacin while a MIC of ≥32 µg/ml for nalidixic acid. The screened isolates include Pseudomonas aeruginosa 64(18.7%), E coli 92(26.8%), Klebsiella pneumoniae 53(15.4%), Salmonella typhi 39(11.4%), Shigella dysenteriae 36(10.5%), Proteus mirabilis 34(9.9%) and Serratia marcescens 25(7.3%). The average resistance of the isolates to the various quinolones ranged from 42.7% to 66.7%. Klebsiella were the most resistant isolates with a mean resistance of 66.7% while Proteus were the less resistant isolates with a mean resistance of 42.7%. Most isolates were resistant to Nalidixic acid followed by norfloxacin while the less resistant were to the pefloxacin. The frequency of qnr genes transfer to EJRifr as recipient ranged from 2 x 10-2 to 6 x 10-6 with an average of 2 plasmids per cell. The molecular weight of the plasmids ranged from

Background: Resistance to antimicrobials of different structural classes including fluoroquinolones has arisen in a multitude of bacterial species both in the community and the hospitals. This may complicate the therapeutic management of infections. Decreased susceptibility to fluoroquinolones arises mainly by singlestep mutations in the gyrA and parC genes, which encode the fluoroquinolones targets, the topoisomerase enzymes, conferring cross resistance to all fluoroquinolones. Accumulation of multiple mutations in several genes confers increasing level of resistance associated with clinical failure. However, even low level resistance can generate therapeutic failure. In 1998, some mobile elements with a potential for the horizontal transfer of the quinolone resistance genes were described. The loci which are responsible for this plasmid- mediated quinolone resistance, which have been designated as qnrA, qnrB and qnrS, have been identified in the Enterobacteriaceae species. Aim: To evaluate the susceptibility pattern of the isolates to various antibiotics and to know the prevalence rate of ciprofloxacin resistance in our hospital. Materials & Methods: A total of 916 gram-negative bacilli (GNB) were isolated from different clinical specimens over a period of nine months, were subjected to antibiotic susceptibility testing. Isolates with resistance or with a decreased susceptibility to ciprofloxacin (£20 mm) were then screened for their minimum inhibitory concentration (MIC) by using the E-test. Results: Out of 916 GNB, 321 (35%) isolates were resistant to ciprofloxacin. The MIC of these isolates ranged from 4 to >32?g/ml. Conclusion: The resistance rate to ciprofloxacin was 35% in our study. Most of the ciprofloxacin resistant isolates were from urinary tract infections (UTI). The ciprofloxacin resistance was also closely associated with multi-drug resistance, thus limiting the treatment options. Ciprofloxacin resistance can be used as a general surrogate marker of multidrug resistance, thus limiting the already restricted treatment options. The considerably high MIC values for ciprofloxacin in this study reflected the extent of the treatment problems for these resistant isolates and a need for the continuous evaluation of the commonly used antibiotics. [ABSTRACT FROM AUTHOR]

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New Delhi metallo-β-lactamase 1 (NDM-1) producers, first identified from patients hospitalized in India, are now reported worldwide. The Indian subcontinent is clearly a main reservoir of NDM-1 producers. In order to slow down the spread of these NDM-1-positive Enterobacteriaceae, first in India and then worldwide, a series of measures must be implemented as soon as possible. These include discouraging the over-the-counter sale of antibiotics, improving basic and extended knowledge on hygiene, and the wide-scale detection of blaNDM-1, in both infecting agents and in the carrier state for at-risk patients. [ABSTRACT FROM AUTHOR]

A multiplex polymerase chain reaction (m-PCR) technique was developed as a rapid and accurate diagnostic tool for identifying five major Gram-negative bacilli - Vibrio vulnificus, V. parahaemolyticus, Aeromonas hydrophila, Chryseobacterium meningosepticum and Edwardsiella tarda- that cause major diseases in cultured aquatic animals in Taiwan. The expected amplicons for V. vulnificus, V. parahaemolyticus, A. hydrophila, C. meningosepticum and E. tarda were 410, 368, 685, 180 and 230 bp, respectively. The assay was shown to be specific for the target pathogens. The sensitivities of detection were estimated to be 20.5 fg∼200 pg of genomic DNA or 102∼104 colony-forming units (cfu) of bacterial isolates when adopted as PCR templates. The m-PCR was capable of simultaneously amplifying target fragments from bacterial genome DNA mixed with the DNA extracted from viscera and tissues taken from fish without affecting the performance of the method. [ABSTRACT FROM AUTHOR]