Aerobic Gram-negative Bacilli Research Articles

Isolated Skin Pantoea Agglomerans Infection: An Entomodermoscopy Description

Pantoea agglomerans is an environmental and agricultural gram-negative aerobic bacilli, and it uncommonly causes skin infections and presents with nonspecific clinical and histological findings. Hereby, we report a unique rare case of isolated cutaneous infection with Pantoea gglomerans with a first entomodermoscopy description.

Etiological factors of bloodstream infections in oncological patients, who was hospitalized at the National Institute of Maria Skłodowska-Curie - National Research Institute in Warsaw in 2020-2022.

The purpose of the study was the microbiological analysis of bloodstream infections in patients hospitalized at the National Institute of Oncology, Maria Skłodowska-Curie - National Research Institute in the period from 01/01/2020 to 31/10/2022. In the period from 01/01/2020 to 31/10/2022, 18,420 blood cultures obtained from patients hospitalized at the NIO-PIB were analysed in the Department of Clinical Microbiology (total for the presence of bacteria and fungi). Culture for the presence of bacteria was carried out in the BactAlert automatic system by bioMerieux, and for fungi in the Bactec FX automatic system by Becton Dickinson. 1,184 strains of bacteria and 32 strains of fungi considered to be the etiological factor of the infection were cultured from clinical samples. Gram-positive bacteria accounted for 61.57%, while Gram-negative bacteria accounted for 32.26% of all isolated bacterial strains. The most frequently cultured strains were Escherichia coli - 13.77% (including 22.1% of ESBL strains), Klebsiella penumoniae - 4.6% (44.4% of ESBL strains, 1.85% of NDM strains), Enterobacter cloacae - 2 .7% (including 40.6% of multi-resistant strains: ESBL (15.6%) or with AmpC derepression (25%), among the non-fermenting bacilli, Pseudomonas aeruginosa was the most frequently cultured - 4.18% (including 3.8% MBL) and Acinetobacter baumannii - 0.8% (including CRAB strains 50%, MBL 10%). Anaerobic microorganisms were responsible for 3.46% of blood infection cases. Yeast- like fungi were a factor in 2.7% of all fungemia cases. From blood samples taken Staphylococci were more frequently isolated directly from a vein or through a central venous catheter than aerobic Gram-negative bacilli (44.7% and 25.3% and 55.6% and 12.5%, respectively). The opposite situation occurred in the case of samples taken simultaneously directly from vein and through a central venous catheter, in which a higher share of aerobic Gram-negative bacilli (46.6%) than staphylococci (32.8%) in causing blood infections was observed. Gram-positive bacteria are the major contributors to bloodstream infections in cancer patients. There is a growing tendency to develop BSI caused by multi-resistant strains.

Antimicrobial Susceptibility of E. coli Isolates from Intra-Abdominal Infections in the Asia-Pacific Region: Trends in Ciprofloxacin, Ceftriaxone, Cefepime, and Piperacillin/Tazobactam Susceptibility.

To investigate the antibiotic susceptibility of Escherichia coli isolates in patients diagnosed with intra-abdominal infections (IAIs) in the Asia-Pacific region. This study was conducted at 50 medical hospitals across 9 countries/regions as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program from 2014 to 2018. Nonduplicate isolates of aerobic and facultative gram-negative bacilli were collected and processed for further antimicrobial susceptibility testing. A total of 10,709 isolates were collected, with E. coli (n=4737, 44.2%) being the leading pathogen causing IAIs, followed by Klebsiella pneumoniae (n=2429, 22.7%) and Pseudomonas aeruginosa (n=931, 8.7%). Community-associated (CA) E. coli isolates generally exhibited higher susceptibility rates for most antibiotics than hospital-associated (HA) isolates. In countries/regions other than Hong Kong, South Korea, and Singapore, HA isolates displayed lower susceptibility rates for multiple classes (≥4) of antibiotics. Among the commonly used antibiotics in IAIs, the overall susceptibility rate for ciprofloxacin was low, with an average of 41.3%. Ceftriaxone susceptibility rates in all selected countries were below 80% starting in 2018, ranging from 23.3% to 75.8%. The cefepime susceptibility rates varied across regions, with consistently reduced susceptibility ranging from 45.5% to 57.8% in India, Thailand, and Vietnam. Piperacillin/tazobactam demonstrated effectiveness against E. coli isolates in almost all countries except India, with a downward trend observed in the Philippines and Taiwan. Carbapenems remained effective against more than 90% of E. coli isolates, except in India. Prudent use of fluoroquinolones and ceftriaxone is advised when treating both CA and HA IAIs in the Asia-Pacific region. The low susceptibility rate of cefepime in India, Thailand, and Vietnam needs careful consideration in its administration. Moreover, the increase in nonsusceptibility to piperacillin/tazobactam in the Philippines and Taiwan poses a potential risk that should be closely monitored.

EFFICACY AND SAFETY OF USING COLISTIN IN NEONATES : A SYSTEMATIC REVIEW

Colistin is a cationic polypeptide antibiotic that belongs to the family of polymyxins and kills bacteria by interfering with the functioning of the bacterial cell. When given intravenously, colistin has the potential to cause a number of potentially harmful side effects, the most prevalent of which is nephrotoxicity. Recent studies have shown that patients who receive therapy with intravenous colistin run a risk of developing decreased kidney function ranging from 7.5% to 18.6% of the time. This risk is higher in patients who are older. However, it is essential to keep in mind that treatment with intravenous colistin, in the same way as treatment with other nephrotoxic drugs can result in conditions such as infection, septic shock, and the failure of several organs, it is vital to keep in mind that treatment with intravenous colistin. The bactericidal actions of colistin are demonstrated to be effective against a significant proportion of Gram-negative aerobic bacilli. It wasn't until the 1950s that it was first used in the United States, but by the 1980s, intravenous versions of the drug had been phased out due to the nephrotoxicity they caused. However, due to a rise in the incidence of illnesses caused by carbapenem-resistant Gram-negative (CRGN) bacteria and a dearth of newly developed antimicrobial drugs that are active against multidrug-resistant Gram-negative germs, the effectiveness of colistin has been called into question once again. The effectiveness of colistin in newborns might range anywhere from 50 to 98 percent. In this particular research endeavor, hyponatremia was identified as a potential adverse impact.

Stenotrophomonas maltophilia pneumonia in critical COVID-19 patients

Stenotrophomonas maltophilia, an environmental aerobic non-fermentative Gram-negative bacilli, has gained attention in many nosocomial outbreaks. COVID-19 patients in intensive care unit have extended hospital stay and are severely immunosuppressed. This study aimed to determine the prevalence and risk factors of S.maltophilia pneumonia in critical COVID-19 patients. A total of 123 COVID-19 patients in ICU admitted between March 2020 and March 2021 were identified from the authors’ institutional database and assessed for nosocomial pneumonia. Demographic data and factors predisposing to S. maltophilia pneumonia were collected and analyzed. The mean age was 66 ± 13 years and 74% were males. Median APACHE and SOFA scores were 13 (IQR = 8–19) and 4 (3–6), respectively. The Median NEWS2 score was 6 (Q1 = 5; Q3 = 8). The Median ICU stay was 12 (Q1 = 7; Q3 = 22) days. S. maltophilia was found in 16.3% of pneumonia patients, leading to a lengthier hospital stay (34 vs. 20 days; p < 0.001). Risk factors for S. maltophilia pneumonia included previous treatment with meropenem (p < 0.01), thrombopenia (p = 0.034), endotracheal intubation (p < 0.001), foley catheter (p = 0.009) and central venous catheter insertion (p = 0.016). S.maltophilia nosocomial pneumonia is frequent in critical COVID-19 patients. Many significant risk factors should be addressed to reduce its prevalence and negative impact on outcomes.

Are There Any Changes in the Causative Microorganisms Isolated in the Last Years from Hip and Knee Periprosthetic Joint Infections? Antimicrobial Susceptibility Test Results Analysis.

PJIs following total hip and knee arthroplasty represent severe complications with broad implications, and with significant disability, morbidity, and mortality. To be able to provide correct and effective management of these cases, an accurate diagnosis is needed. Classically, acute PJIs are characterized by a preponderance of virulent microorganisms, and chronic PJIs are characterized by a preponderance of less-virulent pathogens like coagulase-negative staphylococci or Cutibacterium species. This paper aims to analyze if there are any changes in the causative microorganisms isolated in the last years, as well as to provide a subanalysis of the types of PJIs. In this single-center study, we prospectively included all retrospectively consecutive collected data from patients aged over 18 years that were hospitalized from 2016 through 2022, and patients that underwent a joint arthroplasty revision surgery. A standardized diagnostic protocol was used in all cases, and the 2021 EBJIS definition criteria for PJIs was used. 114 patients were included in our analysis; of them, 67 were diagnosed with PJIs, 12 were acute/acute hematogenous, and 55 were chronic PJIs. 49 strains of gram-positive aerobic or microaerophilic cocci and 35 gram-negative aerobic bacilli were isolated. Overall, Staphylococcus aureus was the most common isolated pathogen, followed by coagulase-negative staphylococci (CoNS). All cases of acute/acute hematogenous PJIs were caused by gram-positive aerobic or microaerophilic cocci pathogens. Both Staphylococcus epidermidis and methicillin-resistant S. aureus were involved in 91.66% of the acute/acute hematogenous PJIs cases. 21.8% of the chronic PJIs cases were caused by pathogens belonging to the Enterobacterales group of bacteria, followed by the gram-negative nonfermenting bacilli group of bacteria, which were involved in 18.4% of the cases. 12 chronic cases were polymicrobial. Based on our findings, empiric broad-spectrum antibiotic therapy in acute PJIs could be focused on the bacteria belonging to the gram-positive aerobic or microaerophilic cocci, but the results should be analyzed carefully, and the local resistance of the pathogens should be taken into consideration.

First case of bloodstream infection due to Caulobacter spp. associated with a postoperative meningitis

Caulobacter species are aerobic Gram-negative bacilli initially isolated from aquatic environments and are an uncommon cause of human infection. We report a case of bloodstream infection and postoperative meningitis caused by Caulobacter spp. that occurred in a 53-year old woman two weeks after surgery for a breast carcinoma cerebral metastasis. Polymerase chain reaction (PCR) amplification and sequencing of the 16S ribosomal DNA identified Caulobacter spp. in three blood cultures and two cerebrospinal fluid (CSF) cultures. Based on our susceptibility results, the patient was successfully treated by a 2-week course of iv imipenem followed by a 4-week course of oral trimethoprim-sulfamethoxazole.

TIVAP-related infection due to Gram-negative aerobic bacilli: should TIVAP stay or should it go?

We aimed to describe the outcome of totally implantable venous-access port (TIVAP)-related infections due to Gram-negative aerobic bacilli (Pseudomonas aeruginosa and other Pseudomonas spp., Acinetobacter spp., and Stenotrophomonas maltophilia), or GNAB, and assess the safety of conservative treatment. We conducted a retrospective study in a French teaching hospital, from January 2016 to December 2020, including adult patients treated for TIVAP-related infection due to GNAB. Success of conservative treatment was defined as a functional TIVAP 3months after infection with no recurrence. We performed a bivariate analysis and analyzed causes for treatment failure. We included 68 patients (53 TIVAP-related bloodstream infections, 11 TIVAP-related infections, and 4 probable TIVAP-related infections) due to GNAB, mostly P. aeruginosa (50/68, 74%). TIVAP removal was initially decided for 49/68 patients (72%). Among the 19/68 (28%) patients with conservative treatment (all for infections caused by P. aeruginosa), 5/19 (26%) had successful treatment, 7/19 (37%) experienced failure (without sepsis or septic shock), 6/19 (32%) died within 3months without TIVAP removal and no signs of infection recurrence, and 1 patient had TIVAP removal as it was no longer required. TIVAP-related infections caused by GNAB frequently require TIVAP removal. Conservative treatment can be performed in selected patients with a non-complicated infection caused by P. aeruginosa, who can benefit from the continuation of antineoplastic chemotherapy or palliative care. Treatment failures were not associated with sepsis or septic shock.

OCCURRENCE OF NON-FERMENTATIVE GRAM-NEGATIVE BACILLI AND THEIR DRUG RESISTANCE IN TERTIARY CARE RURAL HOSPITAL IN LONI, ( M.S.)

Background: Aerobic non-fermenting Gram-negative bacilli (NF-GNB) once consider as a contaminant now associated with life-threatening infection and emerging as multi drug resistant nosocomial pathogens. Aim: Isolation and identication of NF-GNB in all the clinical samples and to determine antibiotic susceptibility pattern of the isolated NF-GNB. Materials And Methods: This study has been conducted in the Department of Microbiology at a tertiary care teaching hospital over a period of one year. NFGNB were isolated and identied from clinical samples by standard procedure and antibiotic sensitivity was performed (according to CLSI guidelines). Out of 1498 clinical specimens, 320 (21.36%) isolates were identied as NF-GNB. Maximu Results: m number of was blood, 90 (28.12%) followed by pus, 84 (26.25%), Pseudomonas Aeruginosa was the commonest isolate, 192 (60%), followed by Pseudomonas species, 58(18.12%) &amp; Acinetobacter boumannii, 46(14.37%). All isolates most of them MDR and were sensitive to polymyxin B, colistin and tigecycline. Multi drug resistant NF-GNB was not uncommon in our hospital. All Conclusion: isolates were sensitive to polymyxin B, colistin and tigecycline. Indiscriminate use of antibiotics against these organisms should be avoided. It is necessary to identify NFGNB &amp; to monitor their susceptibility pattern to guide the clinician for better care and management of patients.

Alarming Levels of Multidrug Resistance in Aerobic Gram-Negative Bacilli Isolated from the Nasopharynx of Healthy Under-Five Children in Accra, Ghana.

Nasopharyngeal carriage of aerobic Gram-negative bacilli (GNB) may precede the development of invasive respiratory infections. We assessed the prevalence of nasopharyngeal carriage of aerobic GNB and their antimicrobial resistance patterns among healthy under-five children attending seven selected day-care centres in the Accra metropolis of the Greater Accra region of Ghana from September to December 2016. This cross-sectional study analysed a total of 410 frozen nasopharyngeal samples for GNB and antimicrobial drug resistance. The GNB prevalence was 13.9% (95% CI: 10.8–17.6%). The most common GNB were Escherichia coli (26.3%), Klebsiella pneumoniae (24.6%), and Enterobacter cloacae (17.5%). Resistance was most frequent for cefuroxime (73.7%), ampicillin (64.9%), and amoxicillin/clavulanic acid (59.6%). The organisms were least resistant to gentamicin (7.0%), amikacin (8.8%), and meropenem (8.8%). Multidrug resistance (MDR, being resistant to ≥3 classes of antibiotics) was observed in 66.7% (95% CI: 53.3–77.8%). Extended-spectrum beta-lactamase (ESBL)-producing bacteria constituted 17.5% (95% CI: 9.5–29.9%), AmpC-producing bacteria constituted 42.1% (95% CI: 29.8–55.5%), and carbapenemase-producing bacteria constituted 10.5% (95% CI: 4.7–21.8%) of isolates. The high levels of MDR are of great concern. These findings are useful in informing the choice of antibiotics in empiric treatment of GNB infections and call for improved infection control in day-care centres to prevent further transmission.

Multi Drug Resistance and Multi Antibiotics Resistance Index of Acinetobacter baumannii Isolated from Hospitals in Port Harcourt Metropolis

Acinetobacter species are aerobic gram-negative bacilli that can cause healthcare-associated infections and can survive for prolonged periods in the environment. Also on the hands of healthcare workers, infection due to Acinetobacter species is a major challenge within the health care facilities and the community in general due to their high drug resistance. The study was aimed at detecting multi drug resistance and multi antibiotics resistance index (MARI) of acinetobacter baumannii isolated from hospitals in Port Harcourt meteropolis in Rivers State, Nigeria. The cross sectional study sampled randomly; as urine and wound swab samples were collected from patients. Acinetobacter spp was isolated using standard microbiological methods. Identification of A. baumannii isolates were done using Phynotypic methods such as culture on Lead Acinetobacter medium and conventional biochemical tests. Antimicrobial susceptibility test was done by Kirby Bauer’s disk diffusion method under Clinical Laboratory Standards Institute (CLSI, 2013) guide Suspect Acinetobacter species were further identified using polymerase chain reaction (PCR) and Sanger sequence typing methods. The results of confirmatory sequence typing of isolates showed that 9 of suspect Acinetobacter spp were A. baumannii. The results of this finding showed presence of A. baumannii species resistant to conventional antibiotics. All isolates demonstrated.MDR and XDR. MARI was high. (&gt;0.2) indicating MDR and high risk. This study established high rate of multidrug resistant Acinetobacter baumanii. There is need for improved sanitary working condition and proper patients’ management to reduce the spread of this health care associated infection as well as a Search for new therapeutic alternative and policies to control the use of antibiotics.

Causative Pathogens Do Not Differ between Early, Delayed or Late Fracture-Related Infections.

Fracture-related infections (FRIs) are classically considered to be early (0–2 weeks), delayed (3–10 weeks) or late (>10 weeks) based on hypothesized differences in causative pathogens and biofilm formation. Treatment strategies often reflect this classification, with debridement, antimicrobial therapy and implant retention (DAIR) preferentially reserved for early FRI. This study examined pathogens isolated from FRI to confirm or refute these hypothesized differences in causative pathogens over time. Cases of FRI managed surgically at three centres between 2015–2019 and followed up for at least one year were included. Data were analysed regarding patient demographics, time from injury and pathogens isolated. Patients who underwent DAIR were also analysed separately. In total, 433 FRIs were studied, including 51 early cases (median time from injury of 2 weeks, interquartile range (IQR) of 1–2 weeks), 82 delayed cases (median time from injury of 5 weeks, IQR of 4–8 weeks) and 300 late cases (median time from injury of 112 weeks, IQR of 40–737 weeks). The type of infection was associated with time since injury; early or delayed FRI are most likely to be polymicrobial, whereas late FRIs are more likely to be culture-negative, or monomicrobial. Staphylococcus aureus was the most commonly isolated pathogen at all time points; however, we found no evidence that the type of pathogens isolated in early, delayed or late infections were different (p = 0.2). More specifically, we found no evidence for more virulent pathogens (S. aureus, Gram-negative aerobic bacilli) in early infections and less virulent pathogens (such as coagulase negative staphylococci) in late infections. In summary, decisions on FRI treatment should not assume microbiological differences related to time since injury. From a microbiological perspective, the relevance of classifying FRI by time since injury remains unclear.

Mini Review Therapeutic Strategies Targeting for Biofilm and Bone Infections.

Bone infection results in a complex inflammatory response and bone destruction. A broad spectrum of bacterial species has been involved for jaw osteomyelitis, hematogenous osteomyelitis, vertebral osteomyelitis or diabetes mellitus, such as Staphylococcus aureus (S. aureus), coagulase-negative Staphylococcus species, and aerobic gram-negative bacilli. S. aureus is the major pathogenic bacterium for osteomyelitis, which results in a complex inflammatory response and bone destruction. Although various antibiotics have been applied for bone infection, the emergence of drug resistance and biofilm formation significantly decrease the effectiveness of those agents. In combination with gram-positive aerobes, gram-negative aerobes and anaerobes functionally equivalent pathogroups interact synergistically, developing as pathogenic biofilms and causing recurrent infections. The adhesion of biofilms to bone promotes bone destruction and protects bacteria from antimicrobial agent stress and host immune system infiltration. Moreover, bone is characterized by low permeability and reduced blood flow, further hindering the therapeutic effect for bone infections. To minimize systemic toxicity and enhance antibacterial effectiveness, therapeutic strategies targeting on biofilm and bone infection can serve as a promising modality. Herein, we focus on biofilm and bone infection eradication with targeting therapeutic strategies. We summarize recent targeting moieties on biofilm and bone infection with peptide-, nucleic acid-, bacteriophage-, CaP- and turnover homeostasis-based strategies. The antibacterial and antibiofilm mechanisms of those therapeutic strategies include increasing antibacterial agents’ accumulation by bone specific affinity, specific recognition of phage-bacteria, inhibition biofilm formation in transcription level. As chronic inflammation induced by infection can trigger osteoclast activation and inhibit osteoblast functioning, we additionally expand the potential applications of turnover homeostasis-based therapeutic strategies on biofilm or infection related immunity homeostasis for host-bacteria. Based on this review, we expect to provide useful insights of targeting therapeutic efficacy for biofilm and bone infection eradication.

Microbiology and Outcomes of Institutionalized Patients With Stroke-Associated Pneumonia: An Observational Cohort Study.

Background: The attributable mortality and microbial etiology of stroke-associated pneumonia (SAP) vary among different studies and were inconsistent.Purpose: To determine the microbiology and outcomes of SAP in the lower respiratory tract (LRT) for patients with invasive mechanical ventilation (MV).Methods: In this observational study, included patients were divided into SAP and non-SAP based on a comprehensive analysis of symptom, imaging, and laboratory results. Baseline characteristics, clinical characteristics, microbiology, and outcomes were recorded and evaluated.Results: Of 200 patients, 42.5% developed SAP after the onset of stroke, and they had a lower proportion of non-smokers (p = 0.002), lower GCS score (p < 0.001), higher serum CRP (p < 0.001) at ICU admission, and a higher proportion of males (p < 0.001) and hypertension (p = 0.039) than patients with non-SAP. Gram-negative aerobic bacilli were the predominant organisms isolated (78.8%), followed by Gram-positive aerobic cocci (29.4%). The main pathogens included K. pneumoniae, S. aureus, H. influenzae, A. baumannii, P. aeruginosa, E. aerogenes, Serratia marcescens, and Burkholderia cepacia. SAP prolonged length of MV (p < 0.001), duration of ICU stay (p < 0.001) and hospital stay (p = 0.027), shortened MV-free days by 28 (p < 0.001), and caused elevated vasopressor application (p = 0.001) and 60-day mortality (p = 0.001). Logistic regression analysis suggested that patients with coma (p < 0.001) have a higher risk of developing SAP.Conclusion: The microbiology of SAP is similar to early phase of HAP and VAP. SAP prolongs the duration of MV and length of ICU and hospital stays, but also markedly increases 60-day mortality.

Pseudomonas aeruginosa Positivity and Sensitivity in Invasive Bloodstream Infections Using Automated Bactec in Tertiary Care Teaching Hospital of North India

Background: Pseudomonas aeruginosa is one of the most commonly encountered gram-negative aerobic bacilli in the differential diagnosis of several probable hospital-acquired infections. Hence, the present study is designed to determine the Pseudomonas positivity and sensitivity in Invasive bloodstream infections using automated Bactec systems as the Antibiotic Sensitivity Profiles differ from one clinical setting to another.&#x0D; Material and Methods: All the blood culture samples received in the Department of Microbiology for culture by Bactec Bd fx from July 2015 to June 2016 were included in the study. The blood culture was observed in the Bactec bd fx system for at least 5 days before they are reported as sterile.&#x0D; Results: Among the total 1275 cultures which were positive for bacteria, 931(73.02%) were positive for gram-negative bacteria. Among the total of 931culture which were positive for gram-negative bacteria, Pseudomonas aeruginosa was isolated in 120(12.89%) cultures. Maximum was found in the age group of 0-1 years 33(27.50%) followed by 19-45 years 26(21.67%). Pseudomonas spp isolates were 100.00% sensitive to Colistin followed by Levofloxacin 84.44%, Piperacillin Tazobactum 82.50%, PB 77.50%, Amikacin 75.00%, Cefepime 75.00% while Pseudomonas spp isolates were 90% resistant to Ampicillin followed by Ceftazidime clavulanic acid 82.64% and Aztreonam 70.31%.&#x0D; Conclusion: Pseudomonas aeruginosa is one of the most common organisms among Gram-Negative isolates and the most commonly isolated in the neonate and infant age group. All the Pseudomonas isolates showed maximum sensitivity to Colistin followed by Levofloxacin, Piperacillin Tazobactum, Amikacin while they were most resistant to Ampicillin followed by Ceftazidime clavulanic acid and Aztreonam. Some alternative novel techniques need to be developed to counter the increasing menace of antibiotic resistance in this particular pathogenic bacteria

Impact of an Antimicrobial Stewardship Program-bundled initiative utilizing Accelerate Pheno\u2122 system in the management of patients with aerobic Gram-negative bacilli bacteremia

PurposeGram-negative bacteria (GNB) are a leading cause of bloodstream infections (BSI) and management is complicated by antibiotic resistance. The Accelerate Pheno™ system (ACC) can provide rapid organism identification and antimicrobial susceptibility testing (AST).MethodsA retrospective, pre-intervention/post-intervention study was conducted to compare management of non-critically ill patients with GNB BSI before and after implementation of a bundled initiative. This bundled initiative included dissemination of a clinical decision algorithm, ACC testing on all GNB isolated from blood cultures, real-time communication of results to the Antimicrobial Stewardship Program (ASP), and prospective audit with feedback by the ASP. The pre-intervention period was January 2018 through December 2018, and the post-intervention period was May 2019 through February 2020.ResultsSeventy-seven and 129 patients were included in the pre-intervention and post-intervention cohorts, respectively. When compared with the pre-intervention group, the time from Gram stain to AST decreased from 46.1 to 6.9 h (p < 0.001), and the time to definitive therapy (TTDT) improved from 32.6 to 10.5 h (p < 0.001). Implementation led to shorter median total duration of antibiotic therapy (14.2 vs 9.5 days; p < 0.001) and mean hospital length of stay (7.9 vs 5.3 days; p = 0.047) without an increase in 30-day readmissions (22.1% vs 14%; p = 0.13).ConclusionImplementation of an ASP-bundled approach incorporating the ACC aimed at optimizing antibiotic therapy in the management GNB BSI in non-critically ill patients led to reduced TTDT, shorter duration of antibiotic therapy, and shorter hospital length of stay without adversely affecting readmission rates.

1587. Activity of Ceftolozane/Tazobactam against Gram-Negative Isolates from Lower Respiratory Tract Infections – SMART United States 2018

BackgroundCeftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor. C/T has been approved by the FDA and EMA for complicated urinary tract infections, complicated intraabdominal infections, and hospital-acquired and ventilator-associated bacterial pneumonia. Using isolates collected in the United States as part of the global SMART surveillance program, we evaluated the activity of C/T and comparators against gram-negative pathogens collected from patients with lower respiratory tract infections (LRTI).MethodsIn 2018, 24 hospitals in the US each collected up to 100 consecutive aerobic or facultative gram-negative bacilli (GNB) from LRTI for a total of 1773 isolates. MICs were determined using CLSI broth microdilution and breakpoints. C/T-nonsusceptible (NS) Enterobacterales and P. aeruginosa isolates were screened by PCR and sequencing for genes encoding β-lactamases.ResultsThe 3 most common species collected from LRTI were P. aeruginosa (35.0% of all collected GNB), K. pneumoniae (10.4%), and E. coli (9.6%). Enterobacterales and P. aeruginosa combined comprised 86.3% of all collected LRTI GNB. The activity of C/T and comparators against GNB from LRTI is shown in the table.C/T was active against 93% of Enterobacterales isolates from LRTI (activity only exceeded by meropenem and amikacin), as well as against 97% of P. aeruginosa and 94% of all Enterobacterales and P. aeruginosa combined (activity only exceeded by amikacin). C/T maintained activity against 69-83% of β-lactam-NS subsets of Enterobacterales and P. aeruginosa combined.Among 67 molecularly characterized C/T-NS Enterobacterales isolates, 19.4% carried KPC, 1.5% acquired AmpC, and 16.4% only extended-spectrum β-lactamases. No acquired β-lactamases were detected in the remaining 62.7% of isolates, of which 92.9% were species with intrinsic AmpC. Among 21 molecularly characterized C/T-NS P. aeruginosa, one isolate carried an IMP-type metallo-β-lactamase, and in the remaining isolates no acquired β-lactamases were detected.Table ConclusionWith its broad coverage of Enterobacterales and P. aeruginosa, C/T can provide an important empiric therapy option for patients with LRTI in the US.DisclosuresSibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Daryl DePestel, PharmD, BCPS-ID, Merck & Co, Inc (Employee) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)

REVIEW ABOUT DIABETES MELLITUS AND URINARY TRACT INFECTIONS

Diabetes mellitus (DM) is a clinical disease correlated with a deficiency of insulin secretion or action. It is one of the leading causes of morbidity and mortality worldwide. The global burden of diabetes is rising due to increasing obesity and population aging. Urinary tract infections (UTI) are common microbial infections known to affect the different parts of the urinary tract accounting for major antibacterial drug consumption. About 150 million UTI cases were diagnosed every year. Urinary tract infections are the most important and most common site of infections in a diabetic patient. Diabetic patients have been found to have a 5-fold frequency of acute pyelonephritis at autopsy than non-diabetics. Most of the urinary tract infections in patients with diabetes are relatively asymptomatic. The presence of this syndrome predisposes to much more severe infections, particularly in patients with acute ketoacidosis, poor diabetic control, diabetic complications such as neuropathy, vasculopathy, and nephropathy. The Gram-negative aerobic bacilli are the large group of bacterial pathogens that cause UTI with few species of Gram-positive bacteria. However, some fungi, parasites, and viruses have also been reported to invade the urinary tract. Urinary tract infection affects women more than men due to several factors such as proximity of the genital tract to the urethra, anatomy of the female urethra, sexual activity, menopause, and pregnancy. Other possible risk factors of UTI include allergy, obesity, diabetes, past history of UTI, contraceptive use, catheter use, and family history.

Cefiderocol Antimicrobial Susceptibility Testing Considerations: the Achilles' Heel of the Trojan Horse?

Cefiderocol (formerly S-649266) is a novel siderophore-conjugated cephalosporin with activity against a broad array of multidrug-resistant (MDR), aerobic Gram-negative bacilli. The siderophore component binds iron and uses active iron transport for drug entry into the bacterial periplasmic space. The cephalosporin moiety is the active antimicrobial component, structurally resembling a hybrid between ceftazidime and cefepime. Like other β-lactam agents, the principal bactericidal activity of cefiderocol occurs via inhibition of bacterial cell wall synthesis by binding of penicillin-binding proteins (PBPs) and inhibiting peptidoglycan synthesis, leading to cell death. Iron concentrations need to be taken into consideration when in vitro antimicrobial susceptibility to cefiderocol is determined. Broth microdilution (BMD) and disk diffusion methods have been developed to determine in vitro activity of cefiderocol. For BMD, cation-adjusted Mueller-Hinton broth (CAMHB) requires iron depletion to provide MICs predictive of in vivo activity. A method to prepare iron-depleted CAMHB (ID-CAMHB) has been described by the Clinical and Laboratory Standards Institute (CLSI). For disk diffusion, standard Mueller-Hinton agar is recommended, presumably because iron is bound in the medium. Currently, clinical FDA and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints and investigational (research-use-only) CLSI breakpoints exist for interpreting cefiderocol susceptibility results for certain Gram-negative bacilli. Cefiderocol does not have clinically relevant activity against Gram-positive or anaerobic organisms. FDA or EUCAST breakpoints should be applied to interpret results for Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii complex for patient care until the investigational status has been removed from CLSI breakpoints. Further clinical outcome data are required to assess the effectiveness of cefiderocol for treatment of other Acinetobacter species (non-baumannii complex) and Stenotrophomonas maltophilia at this time, and, as such, antimicrobial susceptibility testing of these organisms should be limited to research use in the scenario of limited treatment options.

Risk of New Bloodstream Infections and Mortality Among People Who Inject Drugs With Infective Endocarditis

People who inject drugs (PWID) who are being treated for infective endocarditis remain at risk of new bloodstream infections (BSIs) due to ongoing intravenous drug use (IVDU). To characterize new BSIs in PWID receiving treatment for infective endocarditis, to determine the clinical factors associated with their development, and to determine whether new BSIs and treatment setting are associated with mortality. This retrospective cohort study was performed at 3 tertiary care hospitals in London, Ontario, Canada, from April 1, 2007, to March 31, 2018. Participants included a consecutive sample of all PWID 18 years or older admitted with infective endocarditis. Data were analyzed from April 1, 2007, to June 29, 2018. New BSIs and factors associated with their development, treatment setting of infective endocarditis episodes (ie, inpatient vs outpatient), and 90-day mortality. The analysis identified 420 unique episodes of infective endocarditis in 309 PWID (mean [SD] patient age, 35.7 [9.7] years; 213 episodes [50.7%] involving male patients), with 82 (19.5%) complicated by new BSIs. There were 138 independent new BSIs, of which 68 (49.3%) were polymicrobial and 266 were unique isolates. Aerobic gram-negative bacilli (143 of 266 [53.8%]) and Candida species (75 of 266 [28.2%]) were the most common microorganisms. Ongoing inpatient IVDU was documented by a physician in 194 infective endocarditis episodes (46.2%), and 127 of these (65.5%) were confirmed by urine toxicology results. Multivariable time-dependent Cox regression demonstrated that previous infective endocarditis (hazard ratio [HR], 1.89; 95% CI, 1.20-2.98), inpatient treatment (HR, 4.49; 95% CI, 2.30-8.76), and physician-documented inpatient IVDU (HR, 5.07; 95% CI, 2.68-9.60) were associated with a significantly higher rate of new BSIs, whereas inpatient addiction treatment was associated with a significantly lower rate (HR, 0.53; 95% CI, 0.32-0.88). New BSIs were not significantly associated with 90-day mortality (HR, 1.76; 95% CI, 0.78-4.02); significant factors associated with mortality included inpatient infective endocarditis treatment (HR, 3.39; 95% CI, 1.53-7.53), intensive care unit admission (HR, 9.51; 95% CI, 4.91-18.42), and methicillin-resistant Staphylococcus aureus infective endocarditis (HR, 1.77; 95% CI, 1.03-3.03), whereas right-sided infective endocarditis was associated with a significantly lower mortality rate (HR, 0.41; 95% CI, 0.25-0.67). In this study, new BSIs were common in PWID receiving parenteral treatment for infective endocarditis. Discharging patients to outpatient treatment was not associated with an increase in new BSI incidence or mortality; carefully selected PWID may therefore be considered for such treatment.