The efficacy and safety of inhaled antibiotics for pneumonia: A systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of inhaled antibiotics for adults with pneumonia by meta-analysis. METHODS: Literature retrieval was completed through five databases (PubMed, Embase, Cochrane Library, Web of Science and Scopus) by the deadline of May 31, 2024. The process of study selection and data extraction were performed independently by two reviewers. The quality of observational studies and randomized controlled trial (RCT) studies were evaluated by Newcastle Ottawa scale and Jadad scale, respectively. The primary outcomes included mortality, clinical cure, and microbiological cure. Secondary outcomes were recurrence and renal impairment. RESULTS: There were 30 studies were analyzed, including 12 RCT studies and 18 observational studies. Inhaled antibiotics did not significantly reduce mortality in RCT studies (odds ratio (OR) = 1.06, 95 % confidence interval (CI): 0.80-1.41). Inhaled antibiotics were associated with higher rates of clinical cure (OR = 1.47 95%CI: 0.82-2.66 in RCT studies and OR = 2.09, 95%CI: 1.36-3.21 in observational studies) and microbiological cure (OR = 7.00 in RCT studies and OR = 2.20 in observational studies). Subgroup analysis showed patients received inhaled antibiotics combined with intravenous administration and inhaled amikacin had better improvements of mortality, clinical cure and microbiological cure. Inhaled antibiotics were not associated with recurrence. The pooled OR of renal impairment were 0.65 (95%CI: 0.27-1.13; I-squared = 43.5 %, P = 0.124) and 0.63(95%CI: 0.26-1.11; I-squared = 69.0 %, P = 0.110) in RCT studies and observational studies, respectively. CONCLUSIONS: Inhaled antibiotics decreased risk of renal impairment and achieved significant improvements of clinical and microbiological cure in patients with pneumoniae.

Displacement Assay in a Polythiophene Sensor System Based on Supramacromolecuar Disassembly-Caused Emission Quenching.

Exploring new methodologies for simple and on-demand methods of manipulating the emission and sensing ability of fluorescence sensor devices with solid-state emission molecular systems is important for realizing on-site sensing platforms. In this regard, although conjugated polymers (CPs) are some of the best candidates for preparing molecular sensor devices owing to their luminescent and molecular recognition properties, the development of CP-based sensor devices is still in its early stages. In this study, we herein propose a novel strategy for preparing a chemical stimuli-responsive solid-state emission system based on supramacromolecular assembly-induced emission enhancement (SmAIEE). The system was spontaneously developed by mixing only the component polymers (i.e., polythiophene and a transient cross-linking polymer). The proposed strategy can be applied to the facile preparation of molecular sensor devices. The analyte-induced fluorescent response of polythiophene originated from the dynamic displacement of the transient cross-linker in the polythiophene ensemble and the generation of the polythiophene-analyte complex. Our successful demonstration of the spontaneous preparation of the fluorescence sensor system by mixing two component polymers could lead to the development of on-site molecular analyzers including the determination of multiple analytes.

Determination of Aminoglycosides by Ion-Pair Liquid Chromatography with UV Detection: Application to Pharmaceutical Formulations and Human Serum Samples.

Aminoglycosides (AGs) represent a prominent class of antibiotics widely employed for the treatment of various bacterial infections. Their widespread use has led to the emergence of antibiotic-resistant strains of bacteria, highlighting the need for analytical methods that allow the simple and reliable determination of these drugs in pharmaceutical formulations and biological samples. In this study, a simple, robust and easy-to-use analytical method for the simultaneous determination of five common aminoglycosides was developed with the aim to be widely applicable in routine laboratories. With this purpose, different approaches based on liquid chromatography with direct UV spectrophotometric detection methods were investigated: on the one hand, the use of stationary phases based on hydrophilic interactions (HILIC); on the other hand, the use of reversed-phases in the presence of an ion-pairing reagent (IP-LC). The results obtained by HILIC did not allow for an effective separation of aminoglycosides suitable for subsequent spectrophotometric UV detection. However, the use of IP-LC with a C18 stationary phase and a mobile phase based on tetraborate buffer at pH 9.0 in the presence of octanesulfonate, as an ion-pair reagent, provided adequate separation for all five aminoglycosides while facilitating the use of UV spectrophotometric detection. The method thus developed, IP-LC-UV, was optimized and applied to the quality control of pharmaceutical formulations with two or more aminoglycosides. Furthermore, it is demonstrated here that this methodology is also suitable for more complex matrices, such as serum, which expands its field of application to therapeutic drug monitoring, which is crucial for aminoglycosides, with a therapeutic index ca. 50%.

Re-telling the story of aminoglycoside ototoxicity: tales from sub-Saharan Africa.

Background: Aminoglycosides, such as Streptomycin, are cheap, potent antibiotics widely used Sub-Saharan Africa. However, aminoglycosides are the commonest cause of ototoxicity. The limited prospective epidemiological studies on aminoglycoside ototoxicity from Sub-Saharan Africa motivated this study to provide epidemiological information on Streptomycin-induced ototoxicity, identify risk factors and predictors of ototoxicity. Method: A longitudinal study of 153 adults receiving Streptomycin-based anti-tuberculous drugs was done. All participants underwent extended frequency audiometry and had normal hearing thresholds at baseline. Hearing thresholds were assessed weekly for 2 months, then monthly for the subsequent 6 months. Ototoxicity was determined using the ASHA criteria. Descriptive statistics were used to analyze socio-demographic variables. Ototoxicity incidence rate was calculated, and Kaplan-Meier estimate used to determine cumulative probability of ototoxicity. Chi-square test was done to determine parameters associated with ototoxicity and Cox regression models were used to choose the predictors of ototoxicity. Results: Age of participants was 41.43 ± 12.66 years, with a male-to-female ratio of 1:0.6. Ototoxicity was found in 34.6% of the participants, giving an incidence of 17.26 per 1,000-person-week. The mean onset time to ototoxicity was 28.0 ± 0.47 weeks. By 28th week, risk of developing ototoxicity for respondents below 40 years of age was 0.29, and for those above 40 years was 0.77. At the end of the follow-up period, the overall probability of developing ototoxicity in the study population was 0.74. A significant difference in onset of ototoxicity was found between the age groups: the longest onset was seen in <40 years, followed by 40-49 years, and shortest onset in ≥50 years. Hazard of ototoxicity was significantly higher in participants aged ≥50 years compared to participants aged ≤40 years (HR = 3.76, 95% CI = 1.84-7.65). The probability of ototoxicity at 40 g, 60 g and 80 g cumulative dose of Streptomycin was 0.08, 0.43 and 2.34, respectively. Age and cumulative dose were significant predictors of ototoxicity. Conclusion: The mean onset time to Streptomycin-induced ototoxicity was 28 weeks after commencement of therapy. Age and cumulative dose can reliably predict the onset of Streptomycin-induced ototoxicity. Medium to long term monitoring of hearing is advised for patients on aminoglycoside therapy.

The FinO/ProQ-like protein PA2582 impacts antimicrobial resistance in Pseudomonas aeruginosa.

Bacteria employ small regulatory RNAs (sRNA) and/or RNA binding proteins (RBPs) to respond to environmental cues. In Enterobacteriaceae, the FinO-domain containing RBP ProQ associates with numerous sRNAs and mRNAs, impacts sRNA-mediated riboregulation or mRNA stability by binding to 5'- or 3'-untranslated regions as well as to internal stem loop structures. Global RNA-protein interaction studies and sequence comparisons identified a ProQ-like homolog (PA2582/ProQ Pae ) in Pseudomonas aeruginosa (Pae). To address the function of ProQ Pae , at first a comparative transcriptome analysis of the Pae strains PAO1 and PAO1ΔproQ was performed. This study revealed more than 100 differentially abundant transcripts, affecting a variety of cellular functions. Among these transcripts were pprA and pprB, encoding the PprA/PprB two component system, psrA, encoding a transcriptional activator of pprB, and oprI, encoding the outer membrane protein OprI. RNA co-purification experiments with Strep-tagged Pae ProQ protein corroborated an association of ProQ Pae with these transcripts. In accordance with the up-regulation of the psrA, pprA, and pprB genes in strain PAO1ΔproQ a phenotypic analysis revealed an increased susceptibility toward the aminoglycosides tobramycin and gentamicin in biofilms. Conversely, the observed down-regulation of the oprI gene in PAO1ΔproQ could be reconciled with a decreased susceptibility toward the synthetic cationic antimicrobial peptide GW-Q6. Taken together, these studies revealed that ProQ Pae is an RBP that impacts antimicrobial resistance in Pae.

Appropriateness of gentamicin therapeutic drug monitoring at a Middle Eastern tertiary hospital setting: a retrospective evaluation and quality audit.

Introduction: The use of gentamicin in the treatment of infectious diseases requires frequent monitoring to attain the best treatment outcomes. Objective: This study aimed to evaluate the appropriateness of gentamicin therapeutic drug monitoring (TDM) at a tertiary care hospital in Qatar. Methods: A one-year quantitative retrospective chart review of all gentamicin TDM records was conducted. Evidence-based criteria were applied to evaluate the appropriateness of gentamicin TDM in terms of indication, sampling times, and post-analytical actions. Results: Out of 59 captured gentamicin TDM records, 58 gentamicin samples were eligible for evaluation. Overall, gentamicin TDM appropriateness was achieved in 50% (n = 29) of the evaluated records. However, 12% (n = 7) of gentamicin drug concentrations were below the assay quantification limits or were not sampled appropriately. Inappropriate post-analytical actions (22.4%, n = 13) and inappropriate sampling times (44.8%, n = 26) were recorded. Most of the gentamicin blood samples (n = 43; 74.2%) were taken appropriately at steady-state. Inappropriate sampling time relative to the last dose was captured in 31% (n = 18) of the cases. Although 27.6% (n = 16) of gentamicin concentrations were non-therapeutic, continuing gentamicin dosing without adjustment was the most frequent post-analytical action (69.8%, n = 37). Gentamicin dose regimen continuations, dose regimen decreases and dose regimen discontinuations were inappropriately applied in 27% (n = 10), 25% (n = 2) and 14% (n = 1) of the times, respectively. Conclusion: Suboptimal gentamicin TDM practices exist in relation to sampling time and post-analytical actions. Studies exploring setting-specific reasons behind inappropriate TDM practices and methods of its optimisation are needed.

Apramycin has high in vitro activity against Mycobacterium tuberculosis.

Introduction. Aminoglycoside antibiotics such as amikacin and kanamycin are important components in the treatment of Mycobacterium tuberculosis (Mtb) infection. However, more and more clinical strains are found to be aminoglycoside antibiotic-resistant. Apramycin is another kind of aminoglycoside antibiotic that is commonly used to treat infections in animals.Hypothesis. Apramycin may have in vitro activity against Mtb.Aim. This study aims to evaluate the efficacy of apramycin against Mtb in vitro and determine its epidemiological cut-off (ECOFF) value.Methodology. One hundred Mtb isolates, including 17 pansusceptible and 83 drug-resistant tuberculosis (DR-TB) strains, were analysed for apramycin resistance using the MIC assay.Results. Apramycin exhibited significant inhibitory activity against Mtb clinical isolates, with an MIC50 of 0.5 µg ml-1 and an MIC90 of 1 µg ml-1. We determined the tentative ECOFF value as 1 µg ml-1 for apramycin. The resistant rates of multidrug-resistant tuberculosis (MDR-TB), pre-extensively drug-resistant (pre-XDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains were 12.12 % (4/33), 20.69 % (6/29) and 66.67 % (14/21), respectively. The rrs gene A1401G is associated with apramycin resistance, as well as the cross-resistance between apramycin and other aminoglycosides.Conclusion. Apramycin shows high in vitro activity against the Mtb clinical isolates, especially the MDR-TB clinical isolates. This encouraging discovery calls for more research on the functions of apramycin in vivo and as a possible antibiotic for the treatment of drug-resistant TB.

Clinical Outcomes in Patients Who Received a One-Time Aminoglycoside Dose for Extended-Spectrum Beta-Lactamase-Producing Enterobacterales or Pseudomonas aeruginosa Cystitis.

The Infectious Diseases Society of America (IDSA) recommends a single dose of an aminoglycoside for uncomplicated cystitis caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) and difficult-to-treat Pseudomonas aeruginosa. However, there is very little recent clinical evidence to support this recommendation. The objective of this study was to evaluate the safety and efficacy of a single-dose aminoglycoside for cystitis caused by ESBL-E or Pseudomonas aeruginosa. This was a multicenter, retrospective, cohort study. Patients who received ≥3 days of standard of care were compared to patients who received a one-time dose of an aminoglycoside with or without a short course of effective therapy before. The primary outcome was the rate of relapse defined as requiring escalation of antibiotics or starting new antibiotic therapy within 14 days after the completion of antibiotics. A total of 66 patients were included in this study, with 33 patients in each arm. There were more males and complicated cystitis patients in the standard-of-care group. There was no difference found in the rate of relapse. The length of stay was significantly shorter in the aminoglycoside group (4.5 ± 4.4 days vs. 14.1 ± 10.1 days, p < 0.0001). A one-time dose of an aminoglycoside did not increase the risk of relapse and was associated with a shorter length of stay when used to treat cystitis caused by ESBL-E or Pseudomonas aeruginosa.

Awareness and Attitude About Ototoxic Drugs Among Medical Doctors in Arar City, Saudi Arabia.

OBJECTIVES: The purpose of this study was to assess the awareness of ototoxicity among medical doctors in Arar City, Saudi Arabia. METHODS: This is a cross-sectional study based on a pre-formed validated questionnaire (Appendix) that included three sections covering participants' demographic data (three questions), their attitudes (five questions), and knowledge (13 questions) regarding drug-induced ototoxicity. RESULTS: After obtaining their informed consent, 213 physicians from government and private sector health facilities in Arar were enrolled in the study. Interns and general practitioners represented 57.8% of the participants; consultants represented 17.8%. Only 71.8% of participants were interested in drug-induced ototoxicity, while 26.3% considered ototoxicity a rare complication. Approximately 90% of the participants were knowledgeable about the adverse effects of drugs on the vestibulocochlear system, and 26.7% reported having experienced cases of drug-induced ototoxicity in their practice. Participants showed an overall knowledge score about ototoxicity of 9.3±3.27 (out of 14). The knowledge score was significantly higher (p-value=0.0007) for participants with more years of clinical experience. The most widely known ototoxic drug for participants was frusemide (72.3%), followed by aminoglycoside (68.5%), while acetaminophen (44.1%) ototoxicity was the least known among participants. CONCLUSION: Awareness of drug-induced ototoxicity is satisfactory among physicians in the Northern Borders region. However, workshops about all types of drugs with ototoxic effects and the main lines for the management of drug-induced ototoxicity are recommended to increase awareness.

[Pharmacogenetics of aminoglycoside ototoxicity: State of knowledge and practices - Recommendations of the Francophone Network of Pharmacogenetics (RNPGx)]. / Pharmacogénétique de l'ototoxicité des aminosides : état des connaissances et des pratiques ­ recommandations du Réseau francophone de pharmacogénétique (RNPGx).

The administration of aminoglycosides can induce nephrotoxicity or ototoxicity, which can be monitored through pharmacological therapeutic drug monitoring. However, there are cases of genetic predisposition to ototoxicity related to the MT-RNR1 gene, which may occur from the first administrations. Pharmacogenetic analysis recommendations have recently been proposed by the Clinical Pharmacogenetics Implementation Consortium (CPIC). The Francophone Pharmacogenetics Network (RNPGx) provides a bibliographic synthesis of this genetic predisposition, as well as professional recommendations. The MT-RNR1 gene codes for mitochondrial 12S rRNA, which constitutes the small subunit of the mitochondrial ribosome. Three variants can be identified: the variants m.1555A>G and m.1494C>T of the MT-RNR1 gene have a 'high' level of evidence regarding the risk of ototoxicity. The variant m.1095T>C has a 'moderate' level of evidence. The search for these variants can be performed in the laboratory if the administration of aminoglycosides can be delayed after obtaining the result. However, if the treatment is urgent, there is currently no rapid test available in France (a 'point-of-care' test is authorized in Great Britain). RNPGx considers: (1) the search for the m.1555A>G, m.1494C>T variants as 'highly recommended' and the m.1095T>C variant as 'moderately recommended' before the administration of an aminoglycoside (if compatible with the medical context). It should be noted that the level of heteroplasmy detected does not modify the recommendation; (2) pharmacogenetic analysis is currently not feasible in situations of short-term aminoglycoside administration, in the absence of an available analytical solution (rapid test to be evaluated in France); (3) the retrospective analysis in case of aminoglycoside-induced ototoxicity is 'recommended'; (4) analysis of relatives is 'recommended'. Through this summary, RNPGx proposes an updated review of the MT-RNR1-aminoglycoside gene-drug pair to serve as a basis for adapting practices regarding pharmacogenetic analysis related to aminoglycoside treatment.

α-Ketoglutarate downregulates thiosulphate metabolism to enhance antibiotic killing.

Potentiation of the effects of currently available antibiotics is urgently required to tackle the rising antibiotics resistance. The pyruvate (P) cycle has been shown to play a critical role in mediating aminoglycoside antibiotic killing, but the mechanism remains unexplored. In this study, we investigated the effects of intermediate metabolites of the P cycle regarding the potentiation of gentamicin. We found that α-ketoglutarate (α-KG) has the best synergy with gentamicin compared to the other metabolites. This synergistic killing effect was more effective with aminoglycosides than other types of antibiotics, and it was effective against various types of bacterial pathogens. Using fish and mouse infection models, we confirmed that the synergistic killing effect occurred in vivo. Furthermore, functional proteomics showed that α-KG downregulated thiosulphate metabolism. Upregulation of thiosulphate metabolism by exogenous thiosulphate counteracted the killing effect of gentamicin. The role of thiosulphate metabolism in antibiotic resistance was further confirmed using thiosulphate reductase knockout mutants. These mutants were more sensitive to gentamicin killing, and less tolerant to antibiotics compared to their parental strain. Thus, our study highlights a strategy for potentiating antibiotic killing by using a metabolite that reduces antibiotic resistance.

Tobramycin Systemic Absorption in Lung Transplant Recipients Treated With Inhaled Tobramycin: A Cohort Study.

Inhaled tobramycin treatment has been associated with nephrotoxicity in some case reports, but limited data are available about serum levels and its possible systemic absorption in lung transplant recipients (LTR). We conducted a single-center, observational and retrospective study of all adult (>18 years old) LTR treated with inhaled tobramycin for at least 3 days between June 2019 and February 2022. Trough serum levels were collected and >2 µg/mL was considered a high drug level. The primary outcome assessed the presence of detectable trough levels, while the secondary outcome focused on the occurrence of acute kidney injury (AKI) in individuals with detectable trough levels. Thirty-four patients, with a median age of 60 years, were enrolled. The primary indications for treatment were donor bronchial aspirate bacterial isolation (18 patients) and tracheobronchitis (15 patients). In total, 28 patients (82%) exhibited detectable serum levels, with 9 (26%) presenting high levels (>2 µg/mL). Furthermore, 9 patients (26%) developed acute kidney injury during the treatment course. Median trough tobramycin levels were significantly elevated in invasively mechanically ventilated patients compared to non-ventilated individuals (2.5 µg/mL vs. 0.48 µg/mL) (p < 0.001). Inhaled tobramycin administration in LTRs, particularly in those requiring invasive mechanical ventilation, may result in substantial systemic absorption.

Maribacter halichondriae sp. nov., isolated from the marine sponge Halichondria panicea, displays features of a sponge-associated life style.

A new member of the family Flavobacteriaceae (termed Hal144T) was isolated from the marine breadcrumb sponge Halichondria panicea. Sponge material was collected in 2018 at Schilksee which is located in the Kiel Fjord (Baltic Sea, Germany). Phylogenetic analysis of the full-length Hal144T 16S rRNA gene sequence revealed similarities from 94.3 to 96.6% to the nearest type strains of the genus Maribacter. The phylogenetic tree of the 16S rRNA gene sequences depicted a cluster of strain Hal144T with its closest relatives Maribacter aestuarii GY20T (96.6%) and Maribacter thermophilus HT7-2T (96.3%). Genome phylogeny showed that Maribacter halichondriae Hal144T branched from a cluster consisting of Maribacter arenosus, Maribacter luteus, and Maribacter polysiphoniae. Genome comparisons of strain Maribacter halichondriae Hal144T with Maribacter sp. type strains exhibited average nucleotide identities in the range of 75-76% and digital DNA-DNA hybridisation values in the range of 13.1-13.4%. Compared to the next related type strains, strain Hal144T revealed unique genomic features such as phosphoenolpyruvate-dependent phosphotransferase system pathway, serine-glyoxylate cycle, lipid A 3-O-deacylase, 3-hexulose-6-phosphate synthase, enrichment of pseudogenes and of genes involved in cell wall and envelope biogenesis, indicating an adaptation to the host. Strain Hal144T was determined to be Gram-negative, mesophilic, strictly aerobic, flexirubin positive, resistant to aminoglycoside antibiotics, and able to utilize N-acetyl-ß-D-glucosamine. Optimal growth occurred at 25-30 °C, within a salinity range of 2-6% sea salt, and a pH range between 5 and 8. The major fatty acids identified were C17:0 3-OH, iso-C15:0, and iso-C15:1 G. The DNA G + C content of strain Hal144T was 41.4 mol%. Based on the polyphasic approach, strain Hal144T represents a novel species of the genus Maribacter, and we propose the name Maribacter halichondriae sp. nov. The type strain is Hal144T (= DSM 114563T = LMG 32744T).

Stop codon readthrough as a treatment option for epidermolysis bullosa-Where we are and where we are going.

In the context of rare genetic diseases caused by nonsense mutations, the concept of induced stop codon readthrough (SCR) represents an attractive avenue in the ongoing search for improved treatment options. Epidermolysis bullosa (EB)-exemplary for this group of diseases-describes a diverse group of rare, blistering genodermatoses. Characterized by extreme skin fragility upon minor mechanical trauma, the most severe forms often result from nonsense mutations that lead to premature translation termination and loss of function of essential proteins at the dermo-epidermal junction. Since no curative interventions are currently available, medical care is mainly limited to alleviating symptoms and preventing complications. Complementary to attempts of gene, cell and protein therapy in EB, SCR represents a promising medical alternative. While gentamicin has already been examined in several clinical trials involving EB, other potent SCR inducers, such as ataluren, may also show promise in treating the hitherto non-curative disease. In addition to the extensively studied aminoglycosides and their derivatives, several other substance classes-non-aminoglycoside antibiotics and non-aminoglycoside compounds-are currently under investigation. The extensive data gathered in numerous in vitro experiments and the perspectives they reveal in the clinical setting will be discussed in this review.

In vivo screening for toxicity-modulating drug interactions identifies antagonism that protects against ototoxicity in zebrafish.

Introduction: Ototoxicity is a debilitating side effect of over 150 medications with diverse mechanisms of action, many of which could be taken concurrently to treat multiple conditions. Approaches for preclinical evaluation of drug-drug interactions that might impact ototoxicity would facilitate design of safer multi-drug regimens and mitigate unsafe polypharmacy by flagging combinations that potentially cause adverse interactions for monitoring. They may also identify protective agents that antagonize ototoxic injury. Methods: To address this need, we have developed a novel workflow that we call Parallelized Evaluation of Protection and Injury for Toxicity Assessment (PEPITA), which empowers high-throughput, semi-automated quantification of ototoxicity and otoprotection in zebrafish larvae via microscopy. We used PEPITA and confocal microscopy to characterize in vivo the consequences of drug-drug interactions on ototoxic drug uptake and cellular damage of zebrafish lateral line hair cells. Results and discussion: By applying PEPITA to measure ototoxic drug interaction outcomes, we discovered antagonistic interactions between macrolide and aminoglycoside antibiotics that confer protection against aminoglycoside-induced damage to lateral line hair cells in zebrafish larvae. Co-administration of either azithromycin or erythromycin in zebrafish protected against damage from a broad panel of aminoglycosides, at least in part via inhibiting drug uptake into hair cells via a mechanism independent from hair cell mechanotransduction. Conversely, combining macrolides with aminoglycosides in bacterial inhibition assays does not show antagonism of antimicrobial efficacy. The proof-of-concept otoprotective antagonism suggests that combinatorial interventions can potentially be developed to protect against other forms of toxicity without hindering on-target drug efficacy.

A comparison of aminoglycoside antibiotic serum concentrations collected by peripheral veins and peripherally inserted central catheters in adults with cystic fibrosis.

BACKGROUND: People with cystic fibrosis (PwCF) are frequently hospitalized for treatment of pulmonary exacerbation. The Cystic Fibrosis Foundation Pulmonary Guidelines support the use of intravenous aminoglycosides with therapeutic drug monitoring for the treatment of pulmonary exacerbation due to Pseudomonas aeruginosa. Serum intravenous tobramycin concentrations are commonly collected by peripheral venipuncture (PV). Discomfort associated with collection of samples by PV prompts collection via PICC, but the accuracy of intravenous tobramycin serum levels collected by PICC has not been documented in adult PwCF. The primary study objective was to evaluate the difference between intravenous tobramycin serum levels collected by PV and PICC in adult PwCF. METHODS: The authors conducted a prospective case-control study of adult PwCF admitted to University of Utah Health for a pulmonary exacerbation receiving tobramycin by a single lumen PICC. The authors compared tobramycin peak and random serum levels collected by PV and PICC using a detailed flush and waste protocol. RESULTS: The authors analyzed a total of 19 patients with peripheral and PICC samples. The mean tobramycin peak collected by PV (27.2 mcg/mL) was similar to the mean peak collected by PICC (26.9 mcg/mL) (paired samples Wilcoxon signed-rank test, p = .94). The correlation coefficient was 0.88 (95% CI = 0.85-0.91, p < .001). CONCLUSION: Tobramycin serum samples collected by PICC appear to be similar in value to PV collections. Collecting aminoglycoside levels by PICC rather than PV may reduce patient discomfort and improve quality of life. Additional multicenter studies are needed to confirm these results.

A Study of Resistome in Mexican Chili Powder as a Public Health Risk Factor.

Chili powder is an important condiment around the world. However, according to various reports, the presence of pathogenic microorganisms could present a public health risk factor during its consumption. Therefore, microbiological quality assessment is required to understand key microbial functional traits, such as antibiotic resistance genes (ARGs). In this study, metagenomic next-generation sequencing (mNGS) and bioinformatics analysis were used to characterize the comprehensive profiles of the bacterial community and antibiotic resistance genes (ARGs) in 15 chili powder samples from different regions of Mexico. The initial bacterial load showed aerobic mesophilic bacteria (AMB) ranging between 6 × 103 and 7 × 108 CFU/g, sporulated mesophilic bacteria (SMB) from 4.3 × 103 to 2 × 109 CFU/g, and enterobacteria (En) from <100 to 2.3 × 106 CFU/g. The most representative families in the samples were Bacillaceae and Enterobacteriaceae, in which 18 potential pathogen-associated species were detected. In total, the resistome profile in the chili powder contained 68 unique genes, which conferred antibiotic resistance distributed in 13 different classes. Among the main classes of antibiotic resistance genes with a high abundance in almost all the samples were those related to multidrug, tetracycline, beta-lactam, aminoglycoside, and phenicol resistance. Our findings reveal the utility of mNGS in elucidating microbiological quality in chili powder to reduce the public health risks and the spread of potential pathogens with antibiotic resistance mechanisms.

Pangenomic analyses of tuberculosis strains to identify resistomes using computational approaches.

Objective: To locate resistomes in tuberculosis strains, to determine the severity of drug resistance, and to infer its implications with respect to high tuberculosis prevalence in a Third World setting. METHODS: The pangenomic study was conducted from October 2022 to January 2023 in Sir Syed University of Engineering and Technology, Karachi, and comprised 2012-22 data on multiple sequence alignment to assess the genetic evolution of tuberculosis strains. Antibiotic resistance drug classes were identified using the Canadian Antibiotic Resistance Database, which entailed multidrug-resistant and extremely drug-resistant strains. Also, GenBank was used for tuberculosis genome FASTA (fast-all; nucleotide and protein sequence representation) files, prediction of resistome sequences on the basis of Canadian Antibiotic Resistance Database, and multiple sequence alignment was done in Mauve. RESULTS: Evolutionarily, the 6 strains identified were structurally similar with polymorphisms in their core chromosomal regions. Their resistome genes showed perfect hits for isoniazid, rifamycin, cephalosporin, fluoroquinolone, aminoglycosides, penem, penam and cephamycin. Conclusion: Drugs discovered in antibiotic resistance genes are now less effective in treatment, and have the potential to develop into more dangerous bacteria, if not monitored. For treatment, staying long durations in hospitals for quality healthcare and supervision in third world countries is unaffordable.