In recent years, new antimicrobials have been introduced in therapeutics, including new beta-lactam-beta-lactamase inhibitor combinations and cefiderocol in response to therapeutic needs in the face of increasing resistance. There are also different treatment guidelines for infections caused by these microorganisms that have been approved by different professional societies, including those of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Disease Society of America (IDSA) and the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC). All of them are based on scientific evidence, but with differences in the weight of expert opinion in their recommendations. Both ESCMID and IDSA include recommendations for the treatment of extended-spectrum beta-lactamase-producing microorganisms. The IDSA is the only one including AmpC producers, all address the treatment of infections caused by carbapenem-resistant Enterobacterales and Acinetobacter baumannii and multidrug-resistant or difficult-to-treat Pseudomonas aeruginosa, and the IDSA and SEIMC include recommendations on the treatment of Stenotrophomonas maltophilia. Future guidelines should integrate new antimicrobials and new innovative management options not covered by current guidelines.

METHODS: The aim of the guidelines is to provide recommendations on perioperative antibiotic prophylaxis (PAP) in adult inpatients who are carriers of multidrug-resistant Gram-negative bacteria (MDR-GNB) before surgery.
METHODS: These evidence-based guidelines were developed after a systematic review of published studies on PAP targeting the following MDR-GNB: extended-spectrum cephalosporin-resistant Enterobacterales, carbapenem-resistant Enterobacterales (CRE), aminoglycoside-resistant Enterobacterales, fluoroquinolone-resistant Enterobacterales, cotrimoxazole-resistant Stenotrophomonas maltophilia, carbapenem-resistant Acinetobacter baumannii (CRAB), extremely drug-resistant Pseudomonas aeruginosa, colistin-resistant Gram-negative bacteria, and pan-drug-resistant Gram-negative bacteria. The critical outcomes were the occurrence of surgical site infections (SSIs) caused by any bacteria and/or by the colonizing MDR-GNB, and SSI-attributable mortality. Important outcomes included the occurrence of any type of postsurgical infectious complication, all-cause mortality, and adverse events of PAP, including development of resistance to targeted (culture-based) PAP after surgery and incidence of Clostridioides difficile infections. The last search of all databases was performed until April 30, 2022. The level of evidence and strength of each recommendation were defined according to the Grading of Recommendations Assessment, Development and Evaluation approach. Consensus of a multidisciplinary expert panel was reached for the final list of recommendations. Antimicrobial stewardship considerations were included in the recommendation development.
CONCLUSIONS: The guideline panel reviewed the evidence, per bacteria, of the risk of SSIs in patients colonized with MDR-GNB before surgery and critically appraised the existing studies. Significant knowledge gaps were identified, and most questions were addressed by observational studies. Moderate to high risk of bias was identified in the retrieved studies, and the majority of the recommendations were supported by low level of evidence. The panel conditionally recommends rectal screening and targeted PAP for fluoroquinolone-resistant Enterobacterales before transrectal ultrasound-guided prostate biopsy and for extended-spectrum cephalosporin-resistant Enterobacterales in patients undergoing colorectal surgery and solid organ transplantation. Screening for CRE and CRAB is suggested before transplant surgery after assessment of the local epidemiology. Careful consideration of the laboratory workload and involvement of antimicrobial stewardship teams before implementing the screening procedures or performing changes in PAP are warranted. High-quality prospective studies to assess the impact of PAP among CRE and CRAB carriers performing high-risk surgeries are advocated. Future well-designed clinical trials should assess the effectiveness of targeted PAP, including the monitoring of MDR-GNB colonization through postoperative cultures using European Committee on Antimicrobial Susceptibility Testing clinical breakpoints.

Pseudomonas aeruginosa (PA) is the second common Gram-negative bacterium for hospital acquired pneumonia (HAP) in China (16.9%-22.0%). The proportion of PA in community acquired pneumonia (CAP) was about 1.0%, while increased to 1.8%-8.3% in severe CAP. PA accounted for 67.0% of CAP in patients with a history of PA infection, bronchiectasis, very severe chronic obstructive pulmonary disease (COPD) or tracheotomy. Considering the high disease burden of lower respiratory tract infections (LRTIs) caused by PA, together with the progress in this field in recent years, the Pulmonary Infection Assembly of Chinese Thoracic Society updated the \"Chinese expert consensus on the management of lower respiratory tract infections of Pseudomonas aeruginosa in adults (2014 version)\", focusing on pathogen detection, diagnosis, antimicrobial therapy, comprehensive management, infection prevention and control.PA causes both acute and chronic LTRIs. Acute LRTIs mainly include pneumonia (CAP, HAP and ventilator-associated pneumonia), tracheobronchitis, lung abscess and empyema. The diagnosis of chronic LTRIs should be based on a comprehensive assessment of (1) underlying chronic structural lung diseases, such as bronchiectasis, cystic fibrosis, COPD, or immunocompromised conditions; (2) the presence of clinical manifestations of LRTIs; and (3) ≥ two times (at least 3 months apart) of PA detected from eligible lower respiratory tract specimens within 1 year. It is important to distinguish infection from colonization when PA is isolated from lower respiratory tract specimens. Drug susceptibility test is a conventional method for PA resistance detection and serves as a basis for target therapy. When drug susceptibility test shows limited activity of available agents, combined susceptibility test is suggested to select antimicrobial drugs with additive or synergistic effect in vitro for combination therapy. Rapid test of resistance mechanisms of PA isolates, such as carbapenemase phenotype confirmation tests, is recommended if available. It is recommended not to routinely detect resistance genes for choosing therapeutic agents.For patients with acute LRTIs in critical condition or with high risk factors for PA infection, empirical antimicrobial therapy covering PA should be initiated after collecting specimens for microbiological tests. In patients with suspected PA pneumonia who are not critically ill, single antimicrobial drug of anti-PA activity with high lung concentration should be selected for empirical treatment. However, for patients with a serious condition such as sepsis or with risk factors for multidrug-resistant (MDR) PA, a combination of two different classes of antimicrobial drugs that are both potentially susceptible should be used. The antimicrobial regimen should follow pharmacokinetics/pharmacodynamics principles to ensure adequate dosage and administration frequency. For confirmed PA LRTIs, antibiotics should be selected based on drug sensitivity. In patients without significant underlying diseases, single therapy of an active antimicrobial with adequate pulmonary concentration is recommended rather than combination therapy; when all the available active agents have poor intrapulmonary concentrations, combination therapy is obligatory. For LRTIs caused by carbapenem-resistant PA (CRPA) or difficult-to-treat resistance PA (DTR-PA), if an agent of new enzyme inhibitor, such as ceftolozane/tazobactam, ceftazidime/avibactam, and imipenem/cilastatin/relebactam shows in vitro sensitivity, it is recommended as the first-line choice; cefiderocol may serve as the second-line treatment. Combination therapy based on polymyxins may also be considered. Other potentially successful approaches for drug-resistant PA LRTIs include extended infusion time of β-lactams, combination therapy and inhaled antimicrobial therapy.In patients with underlying chronic structural lung diseases, the antimicrobial regimen (drug, dosage, route of administration, and duration of therapy) should be decided according to clinical features, drug sensitivity, and treatment goals (control of exacerbated symptoms, eradication of new-emerging PA, or prevention of flare-ups in patients with frequent exacerbation).Along with antimicrobial therapy, comprehensive care including airway clearance therapy (ACT), oxygen therapy, nutritional support and organ function protection should be provided. From the perspective of nosocomial infection prevention and control, isolation and prophylaxis of contact transmission are recommended to block PA transmission in addition to standard prevention measures. Targeted active screening, timely monitoring and feedback can help the prevention and control of MDR-PA. The systemic and topical use of prophylactic antimicrobials is not recommended.
铜绿假单胞菌是难治性下呼吸道感染最常见致病菌之一，由于其耐药严重和易形成生物被膜，特别是近10多年来碳青霉烯类耐药株的出现，使其治疗更为困难；同时新的治疗药物和治疗策略不断问世，有必要加以评估以指导临床合理应用。中华医学会呼吸病学分会感染学组在《铜绿假单胞菌下呼吸道感染诊治专家共识（2014年版）》的基础上进行更新，并以临床诊治和预防的思路和技术为重点，以期为临床医生规范化诊治铜绿假单胞菌下呼吸道感染提供切实可行的参考。.

The main objective of this study was to propose a common definition of multidrug-resistant gram-negative organisms (GN-MDRO), which may be used for epidemiological surveillance and benchmarking.
In this retrospective data analysis, we used interpreted qualitative susceptibility data (SIR) from blood culture isolates of different gram-negative microorganisms from the ANRESIS database from 2017-2021. We first analysed testing algorithms used by different Swiss laboratories and investigated cross-resistance patterns within antibiotic groups. Comparing these data with existing international definitions, we developed two different GN-MDRO definitions, an extended one for surveillance purposes (ANRESIS-extended) and a more stringent one for clinical purposes, aimed primarily at the identification of difficult-to-treat GN-MDRO (ANRESIS-restricted). Using these novel algorithms, the rates of invasive GN-MDRO identified in our national dataset were compared with international and national definitions: the European Centre for Disease Prevention and Control (ECDC) definition, the Commission for Hospital Hygiene and Infection (KRINKO) definition and the definition proposed by the University Hospital Zurich.
SIR data of a total of 41,785 Enterobacterales, 2,919 , and 419 spp. isolates were used for the analyses. Five antibiotic categories were used for our MDRO definition: aminoglycosides, piperacillin-tazobactam, third- and fourth-generation cephalosporins, carbapenems and fluoroquinolones. Large differences were found between the testing algorithms of the different laboratories. Cross-resistance analysis within an antibiotic group revealed that the substance most likely to be effective against a particular gram-negative bacterium was not preferentially tested (e.g. amikacin for the aminoglycosides). For all bacterial species tested, the highest rates of multidrug-resistant isolates were found using the ECDC-MDR definition, followed by the ANRESIS-extended definition. The number of MDR-Enterobacterales identified using the ANRESIS-restricted definition (n = 627) was comparable to those identified using the KRINKO (n = 622) and UHZ definitions (n = 437). However, the isolates classified as MDR-Enterobacterales according to the KRINKO, UHZ and ANRESIS-restricted definitions (total n = 870) differed considerably. Only 242 of the isolates (27.8%) were uniformly classified as MDRO according to the KRINKO, UHZ and ANRESIS-restricted definitions. Comparable findings were made for Klebsiella spp. and Pseudomonas aeruginosa.
The application of different MDRO definitions leads to significant differences in not only MDRO rates but also the isolates that are eventually classified as MDRO. Therefore, defining a nationwide MDRO algorithm is crucial if data are compared between hospitals. The definition of a minimal antibiotic susceptibility testing panel would improve comparability further.

Management of patients with infections caused by multidrug-resistant organisms is challenging and requires a multidisciplinary approach to achieve successful clinical outcomes. The aim of this paper is to provide recommendations for the diagnosis and optimal management of these infections, with a focus on targeted antibiotic therapy. The document was produced by a panel of experts nominated by the five endorsing Italian societies, namely the Italian Association of Clinical Microbiologists (AMCLI), the Italian Group for Antimicrobial Stewardship (GISA), the Italian Society of Microbiology (SIM), the Italian Society of Infectious and Tropical Diseases (SIMIT) and the Italian Society of Anti-Infective Therapy (SITA). Population, Intervention, Comparison and Outcomes (PICO) questions about microbiological diagnosis, pharmacological strategies and targeted antibiotic therapy were addressed for the following pathogens: carbapenem-resistant Enterobacterales; carbapenem-resistant Pseudomonas aeruginosa; carbapenem-resistant Acinetobacter baumannii; and methicillin-resistant Staphylococcus aureus. A systematic review of the literature published from January 2011 to November 2020 was guided by the PICO strategy. As data from randomised controlled trials (RCTs) were expected to be limited, observational studies were also reviewed. The certainty of evidence was classified using the GRADE approach. Recommendations were classified as strong or conditional. Detailed recommendations were formulated for each pathogen. The majority of available RCTs have serious risk of bias, and many observational studies have several limitations, including small sample size, retrospective design and presence of confounders. Thus, some recommendations are based on low or very-low certainty of evidence. Importantly, these recommendations should be continually updated to reflect emerging evidence from clinical studies and real-world experience.

Antimicrobial drug resistance is one of the major threats to global health. It has made common infections increasingly difficult or impossible to treat, and leads to higher medical costs, prolonged hospital stays and increased mortality. Infection rates due to multidrug-resistant organisms (MDRO) are increasing globally. Active agents against MDRO are limited despite an increased in the availability of novel antibiotics in recent years. This guideline aims to assist clinicians in the management of infections due to MDRO. The 2019 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group, comprising of infectious disease specialists from 14 medical centers in Taiwan, reviewed current evidences and drafted recommendations for the treatment of infections due to MDRO. A nationwide expert panel reviewed the recommendations during a consensus meeting in Aug 2020, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes recommendations for selecting antimicrobial therapy for infections caused by carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales, and vancomycin-resistant Enterococcus. The guideline takes into consideration the local epidemiology, and includes antimicrobial agents that may not yet be available in Taiwan. It is intended to serve as a clinical guide and not to supersede the clinical judgment of physicians in the management of individual patients.

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Guidelines for pneumonia recommend empiric dual antipseudomonal therapy in patients with specific risk factors. However, there is lack of consensus on when to use dual antipseudomonal therapy as the recommendations are rated as weak, based on low-quality evidence.
The objectives of this study were to develop combination antibiograms to assess the susceptibility of Pseudomonas aeruginosa (P. aeruginosa) in respiratory cultures to combinations of empiric antibiotics and to use combination antibiograms to delineate the impact of specific risk factors for which guidelines recommend dual antipseudomonal therapy.
A retrospective cohort study was conducted of adults hospitalized with pneumonia with positive respiratory cultures for P. aeruginosa between September 2014 and September 2018. Data collected included demographics, antimicrobial susceptibility results, and risk factors for which guidelines recommend dual antipseudomonal therapy. Combination antibiograms were developed and logistic regression was performed to identify risk factors for nonsusceptibility to beta-lactams.
Eight hundred nineteen patients were included and 72% received antibiotics. Beta-lactam susceptibility ranged from 58% to 69% and addition of a fluoroquinolone or aminoglycoside resulted in statistically significant increases in susceptibility. However, only addition of tobramycin or amikacin provided susceptibility rates approaching or exceeding 90% stratified by pneumonia type and risk factors. Presence of guideline-based risk factors generally resulted in reduced susceptibility rates. Logistic regression identified three risk factors associated with nonsusceptibility to beta-lactams: intravenous antibiotics in the previous 90 days, nursing home residence, and mechanical ventilation at onset. The cumulative presence of each additional risk factor affected beta-lactam susceptibility rates, which were 93% in the absence of any risk factors and 39% when all three risk factors co-existed.
Risk factors necessitating dual antipseudomonal therapy for pneumonia should be locally validated. When dual antipseudomonal therapy is indicated, tobramycin or amikacin have the best likelihood of providing adequate in vitro activity.

Antimicrobial resistance is an important global issue that impacts the efficacy of established antimicrobial therapy. This is true globally and within the Arab countries of the Middle East, where a range of key Gram-negative pathogens pose challenges to effective therapy. There is a need to establish effective treatment recommendations for this region given specific challenges to antimicrobial therapy, including variations in the availability of antimicrobials, infrastructure and specialist expertise. This consensus provides regional recommendations for the first-line treatment of hospitalized patients with serious infections caused by World Health Organization critical priority Gram-negative pathogens Acinetobacter baumannii and Pseudomonas aeruginosa resistant to carbapenems, and Enterobacteriaceae resistant to carbapenems and third-generation cephalosporins. A working group comprising experts in infectious disease across the region was assembled to review contemporary literature and provide additional consensus on the treatment of key pathogens. Detailed therapeutic recommendations are formulated for these pathogens with a focus on bacteraemia, nosocomial pneumonia, urinary tract infections, skin and soft tissue infections, and intra-abdominal infections. First-line treatment options are provided, along with alternative agents that may be used where variations in antimicrobial availability exist or where local preferences and resistance patterns should be considered. These recommendations take into consideration the diverse social and healthcare structures of the Arab countries of the Middle East, meeting a need that is not filled by international guidelines. There is a need for these recommendations to be updated continually to reflect changes in antimicrobial resistance in the region, as well as drug availability and emerging data from clinical trials.