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Treatment options for Achromobacter xylosoxidans are limited. Eight cystic fibrosis patients with A. xylosoxidans were treated with 12 cefiderocol courses. Pretreatment in vitro resistance was seen in 3 of 8 cases. Clinical response occurred after 11 of 12 treatment courses. However, microbiologic relapse was observed after 11 of 12 treatment courses, notably without emergence of resistance. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides are important players of the innate host defence against invading microorganisms. The aim of this study was to evaluate the activity of airway antimicrobial peptides against the common cystic fibrosis (CF) pathogen Pseudomonas aeruginosa , and to compare it to the emerging multi-drug resistant CF pathogens Achromobacter xylosoxidans and Stenotrophomonas maltophilia. Clinical bacterial isolates from CF patients were used, and the antimicrobial activity of human beta-defensin 2 and 3, LL37 and lysozyme was evaluated using radial diffusion assay and viable counts. The cell surface zeta potential was analysed to estimate the net charge at the bacterial surface. Of the bacterial species included in the study, A. xylosoxidans was the most resistant to antimicrobial peptides, whereas P. aeruginosa was the most susceptible. The net charge of the bacterial surface was significantly more negative for P. aeruginosa compared to A. xylosoxidans , which may in part explain the differences in susceptibility. [ABSTRACT FROM AUTHOR]

This study investigated the genetic basis of multidrug resistance in two strains of Achromobacter xylosoxidans isolated from patients attending a hospital in Thailand in 2012. These isolates were highly resistant to cephalosporins, aminoglycosides, fluoroquinolones, co-trimoxazole and carbapenems. Whole genome sequencing revealed that the two isolates were not clonally related and identified a carbapenem resistance gene-habouring integron (In687), residing in a novel genomic island, AcGI1. This In687 shares 100% identical nucleotide sequence with ones found in Acinetobacter baumannii Aci 16, isolated from the same hospital in 2007. We report the first analysis of multidrug-resistant A. xylosoxidans isolated in Thailand, and the first example of this island in A. xylosoxidans. Our data support the idea that resistance has spread in Thailand via horizontal gene transfer between species and suggest the possibility of A. xylosoxidans may serve as a reservoir of antibiotic resistance, especially in hospital setting. [ABSTRACT FROM AUTHOR]

Background Hospital reservoirs of Achromobacter xylosoxidans , responsible for nosocomial infections, are poorly known. Methods We examined the growth, survival and biofilm formation of five A. xylosoxidans strains for up to 2 y in distilled, dialysis or microfiltered water. Each strain was inoculated at 102 CFU/ml without adding nutrients. Results All strains grew at a level of 3x103 to 1.5x107 CFU/ml; each strain showed a preferred water type. Strains isolated from quaternary ammoniums showed the highest ability to grow and form biofilms in nutrient-poor waters. Conclusion Medical waters and notably sterile distilled water bottles appear to be long-lasting reservoirs of A. xylosoxidans. [ABSTRACT FROM AUTHOR]

The article offers information on the Achromobacter xylosoxidans which described as being resistant to antiseptics and disinfectants. It mentions that bacterial suspensions in rich media and in distilled water were inoculated into eight antiseptics or disinfectants under conditions of use; and highlights a relationship between starvation and survival in antiseptics and disinfectants.

Patients suffering from cystic fibrosis ( CF) develop chronic lung infections because of highly viscous mucus, where bacteria can form biofilms. In this study, we investigated the microorganisms present in the lungs of end-stage and non-end-stage patients using standard culturing techniques and molecular methods. Tissue and sputum samples ( n = 34) from explanted lungs of five end-stage patients were examined along with routine expectorates ( n = 15) from 13 patients with non-end-stage CF, representing earlier stages of chronic lung infections. Previously, using peptide nucleic acid ( PNA) fluorescence in situ hybridization ( FISH), we have shown that Pseudomonas aeruginosa was the sole pathogen in end-stage CF lungs ( Pediatr Pulmonol 2009, 44: 547). In this study, this tendency was supported by the results of real-time PCR, confirming previous results obtained by standard culturing and 16 S rRNA gene analysis ( J Clin Microbiol 2011, 49: 4352). Conversely, the non-end-stage patients were found to harbor several species by culturing. PNA FISH confirmed heterogeneous microbiota and showed that the bacteria were located in monospecies aggregates with no apparent physical interaction between the different microcolonies. In conclusion, standard culturing identifies the dominating pathogens, which seem to reside in monospecies microcolonies. The possibility of signaling between the distinct microcolonies still has to be verified and elucidated. [ABSTRACT FROM AUTHOR]

In previous work, only one culture (strain TA12) from a pristine site was reported to utilize the xenobiotic compound p-toluenesulfonate (TSA) as a sole source of carbon and energy for aerobic growth. 'Strain TA12' has now been recognized as a community of three bacteria: Achromobacter xylosoxidans TA12-A, Ensifer adhaerens TA12-B and Pseudomonas nitroreducens TA12-C. Achromobacter xylosoxidans TA12-A and E. adhaerens TA12-B were identified as the TSA degraders. These two organisms contain several tsa genes from the Tn tsa cluster described previously in Comamonas testosteroni T-2 and use the tsa pathway. Apparently, due to vitamin auxotrophy, the growth of the pure cultures with TSA was markedly slower than the growth of the community with TSA. The third bacterium ( P. nitroreducens) TA12-C is, then, a provider of essential vitamins for the TSA degraders and occurs at a low frequency. [ABSTRACT FROM AUTHOR]

Pulmonary exacerbations in cystic fibrosis (CF) are frequent events and account for a substantial proportion of the burden of morbidity and mortality in this disease. Antibacterial therapies to treat pulmonary exacerbations are instituted empirically and are individualized based on both patient factors (severity of exacerbation, frequency of exacerbation, recent courses of anti-infectives) and pathogen factors (previously isolated pathogens and in vitro predicted susceptibilities). However, the epidemiology of pathogens infecting CF airways is changing, with increased incidence of methicillin-resistant Staphylococcus aureus (MRSA), drug-resistant Pseudomonas aeruginosa and other Gram-negative non-fermenters such as Stenotrophomonas maltophilia and Achromobacter xylosoxidans. Accordingly, a great need for new and novel agents for the management of acute exacerbations in CF exists. While several antibiotics have recently been approved or are close to approval for clinical use, frequently their emphasis has been for Gram-positive, and specifically MRSA-related, disease. Despite this, these agents may have a role in CF-related exacerbations. This article reviews the spectrum of activity, pharmacokinetics and clinical and theoretical evidence for the use of newer agents including tigecycline, doripenem and ceftobiprole in the management of CF pulmonary exacerbations. Appropriate use of these agents in CF will require detailed CF-specific pharmacokinetic and pharmacodynamic data. [ABSTRACT FROM AUTHOR]

Abstract: Amidases are very important enzymes for industrial biocatalysis. We scored a novel amidase by screening the Achromobacter xylosoxidans gene library with cephalosporin analogous amides. The gene coding for the enzyme, designated ana, was cloned, sequenced and overexpressed in Escherichia coli. Sequence analysis of ana showed it to be an amidase signature family member. Interestingly, we noted that almost all Ana homologous amidases are from human pathogens responsible for chronic lung infections. Knowing the genetic context of Ana and its homologous amidases, we suggest that they could be a part of transposon structure. Ana can efficiently hydrolyze a series of cephalosporin analogous amides, including amides with an aninine, p-nitro-aninine, and β-naphthylamine moiety, while cephalosporin could not serve as its substrate. [Copyright &y& Elsevier]

Background Achromobacter xylosoxidans is a highly resistant Gram-negative bacterium that causes chronic infections in patients with cystic fibrosis (CF). Treatment options for A. xylosoxidans are limited. In the peri-lung transplant setting, the treatment of A. xylosoxidans infections is especially challenging. Cefiderocol is a novel siderophore cephalosporin antibiotic with broad anti-Gram-negative activity, including against A. xylosoxidans. We report here two cases of compassionate use of cefiderocol in CF lung transplant recipients with A. xylosoxidans infection. Methods Cefiderocol was obtained through compassionate use from its manufacturer, with approval from the local Institutional Review Board. In the first case, it was used as salvage treatment, and in the second case as a planned part of the peri-transplant regimen. Results A male in his 20s with CF and a trimethoprim-sulfamethoxazole (TMP-SMX) allergy was chronically colonized by A. xylosoxidans , which was sensitive only to piperacillin–tazobactam (PIP-TAZ), and TMP-SMX. After lung transplant, he developed A. xylosoxidans bacteremia, and extended-infusion PIP-TAZ was started. Repeat bronchoscopy grew A. xylosoxidans. Due to lack of improvement, cefiderocol was added to PIP-TAZ with rapid clinical improvement. However, after completing his course, he was readmitted with A. xylosoxidans pneumonia. He was treated with 6 weeks of cefiderocol and imipenem and has been well since with an 8-month follow-up. In the second case, cefiderocol was used as part of the planned peri-transplant regimen for a female with CF in her late teens, with chronic A. xylosoxidans colonization, which was intermediate to PIP-TAZ, and resistant to all other drugs tested. Her native lungs grew 4+ A. xylosoxidans at the time of explant. Post-transplant, she was treated with 5 weeks of meropenem and 6 weeks of cefiderocol. At four-month follow-up, she is doing well. However, she is asymptomatically colonized with A. xylosoxidans post-transplant. Isolates from both cases were susceptible to cefiderocol (case #1 MIC = 0.12; case #2 pretreatment MIC = 1, post-treatment MIC. Conclusion Cefiderocol may be a useful option for lung transplant recipients with A. xylosoxidans infections. Disclosures Anne Lachiewicz, MD, MPH, MicroGenDx: Consultant; Shionogi: Consultant. [ABSTRACT FROM AUTHOR]

Background Achromobacter species are non-fermentous Gram-negative bacilli that are primarily found in contaminated soil or water, but is rare in human. Although their low virulence, Achromobacter xylosoxidans is considered one of the emerging nosocomial agents in immunocompromised patients, including those with hematologic malignancy, diabetes, and renal failure. This organisms can cause pneumonia, catheter-related blood stream infection, urinary tract infection, and meningitis. We investigated the clinical manifestations and outcomes associated with A. xylosoxidans infection in a mid-sized community-based hospital in Korea. Methods We retrospectively analyzed all consecutive episodes of A. xylosoxidans in a mid-sized community-based hospital from October 2015 to April 2019. Results A total 181 clinical isolates of A. xylosoxidans were obtained from 123 patients. Of these, 117 (95%) had nosocomial infection that mostly received previous antibiotic therapy. A. xylosoxidans was isolated from respiratory tract (68%, 84/123), peritoneal fluid (11%, 13/123), urine (8%, 10/123) and blood (6%, 7/123). Seven cases of A. xylosoxidans bacteremia was associated with intravenous catheter sepsis. Seventy-eight cases (63%) had polymicrobial infection; P. aeruginosa (n = 21) was most commonly coisolates organisms, followed by S. maltophilia (n = 20) and methicillin-resistant S. aureus (n = 15). The main underlying diseases were neurologic disease (41%), diabetes mellitus (36%), and solid cancer (25%). Of these, 53 patients (43%) were categorized as in an immunocompromised state. The in-hospital mortality rate was 23%. Based on multivariate analysis, neurologic disease (hazard ratio [HR]: 1.23, 95% confidence interval [CI]: 0.08–0.67; P = 0.007) and the age-adjusted Charlson comorbidity score (HR: 1.31% CI: 1.038–1.65; P = 0.02) were associated with increased mortality. Conclusion We concludes that, though rare, A. xylosoxidans could be pathogenic in immunocompromised patients who are in hospital. A. xylosoxidans can cause nosocomial infection and bacteremia is mostly originating from intravenous catheter. The potential impact on the clinical outcome, further investigations are required to delineate the role of A. xylosoxidans. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Newer Antibacterial Agents and Their Potential Role in Cystic Fibrosis Pulmonary Exacerbation Management," by M. D. Parkins and J. S. Elborn in the 2010 issue.