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BackgroundFluoroquinolones are some of the most used antimicrobial agents for the treatment of Pseudomonas aeruginosa. This study aimed at exploring the differential activity of ciprofloxacin and levofloxacin on the selection of resistance among P. aeruginosa isolates at our medical center.Methods233 P. aeruginosa clinical isolates were included in this study. Antimicrobial susceptibility testing (AST) was done using disk diffusion and broth microdilution assays. Random Amplification of Polymorphic DNA (RAPD) was done to determine the genetic relatedness between the isolates. Induction of resistance against ciprofloxacin and levofloxacin was done on 19 isolates. Fitness cost assay was done on the 38 induced mutants and their parental isolates. Finally, whole genome sequencing was done on 16 induced mutants and their 8 parental isolates.ResultsAST results showed that aztreonam had the highest non-susceptibility. RAPD results identified 18 clusters. The 19 P. aeruginosa isolates that were induced against ciprofloxacin and levofloxacin yielded MICs ranging between 16 and 256 μg/mL. Levofloxacin required fewer passages in 10 isolates and the same number of passages in 9 isolates as compared to ciprofloxacin to reach their breakpoints. Fitness cost results showed that 12 and 10 induced mutants against ciprofloxacin and levofloxacin, respectively, had higher fitness cost when compared to their parental isolates. Whole genome sequencing results showed that resistance to ciprofloxacin and levofloxacin in sequenced mutants were mainly associated with alterations in gyrA, gyrB and parC genes.ConclusionUnderstanding resistance patterns and risk factors associated with infections is crucial to decrease the emerging threat of antimicrobial resistance.

BackgroundThe coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Secondary bacterial infections are associated with unfavorable outcomes in respiratory viral infections. This study aimed at determining the prevalence of secondary bacterial infections in COVID-19 patients admitted at a tertiary medical center in Lebanon.MethodologyFrom May till November, 2020, a total of 26 Gram-negative isolates were recovered from 16 patients during the course of their COVID-19 infection with Escherichia coli being the most prevalent. The isolates were assessed for their antimicrobial susceptibility by broth microdilution against 19 antimicrobial agents from different classes. Whole genome sequencing of 13 isolates allowed the mining of antimicrobial resistance (AMR) determinants as well as mobile genetic elements and sequence types (ST). Finally, broth microdilution with three different efflux pump inhibitors [theobromine, conessine and PheArg-β-naphthylamide (PAβN)] was done.ResultsAntimicrobial susceptibility testing showed that out of the 26 Gram-negative isolates, 1 (4%) was extensively drug resistant and 14 (54%) were multi-drug resistant (MDR). Whole genome sequencing results revealed a plethora of AMR determinants among the 13 sequenced isolates. Moreover, the 9 Enterobacterales and 4 Pseudomonas aeruginosa sequenced isolates belonged to 9 and 2 different ST, respectively. Using a variety of efflux pump inhibitors we demonstrated that only PAβN had a significant effect when combined with levofloxacin, and the latter regained its activity against two P. aeruginosa isolates.ConclusionThe identification of carbapenem and colistin resistant Gram-negative bacilli causing secondary bacterial infections in critical patients diagnosed with COVID-19 should be of high concern. Additionally, it is crucial to monitor and track AMR, post-COVID pandemic, in order to better understand the effect of this disease on AMR exacerbation.

PurposeThe use of carbapenem before and after implementation of an antimicrobial stewardship-led carbapenem-sparing strategy at a tertiary care center in Lebanon was evaluated.MethodsA retrospective, observational chart review was performed on all hospitalized pediatric and adult patients who received carbapenem therapy during January 2019 and January 2020. Patients who started their regimen before January or received carbapenems for less than 24 hours were excluded. Primary outcomes included the appropriateness of physician prescribing patterns and pharmacists’ interventions, as well as appropriateness and response rates of the latter. Secondary outcomes included the carbapenem defined daily dose (DDD) and days of therapy (DOT). Descriptive statistics were used in the analysis and a p-value < 0.05 was considered to be statistically significant.ResultsA total of 157 and 150 patients charts were reviewed in January 2019 and January 2020, respectively. There was no difference in baseline characteristics except for inpatient services and rates of isolated multidrug-resistant organisms. When comparing the two timelines, the appropriateness of physicians’ prescribing patterns increased in terms of empirical therapy, targeted therapy, and duration of therapy but the results were not statistically significant. Pharmacists’ interventions significantly increased with regards to the duration of therapy (p=

Monotherapeutic options for carbapenem resistant infections are limited. Studies suggest that combination therapy may be associated with better outcomes than monotherapies. However, this is still controversial. This study assessed, the efficacy of combination therapy against carbapenem resistant Enterobacteriaceae harboring singly various ESBL or carbapenemase encoding genes. Thus, four isolates harboring either blaCTXM-15, blaCTXM-15 and blaOXA-48, blaNDM-1, or blaKPC-2 genes were selected for testing. Minimal Inhibitory Concentration (MIC) was determined by broth dilution method. Gene transcript levels on single and combined treatments were done in vitro and in vivo by q RT-PCR. Assessment of treatments was done in BALB/c mice according to a specific protocol. As such, the qRT-PCR revealed a significant decrease of transcript levels in all isolates upon using rifampicin or tigecycline, singly or in combination with colistin. However, variable levels were obtained using colistin singly or in combination with meropenem or fosfomycin. In vivo assessment showed that all combinations used were effective against isolates harboring blaCTXM-15, blaOXA-48, and blaNDM-1. Conversely, the most significant combination against the isolate harboring blaKPC-2 gene was colistin with carbapenem, fosfomycin, or kanamycin. As a conclusion, combination therapy selected based on the type of carbapenemase produced, appeared to be non-toxic and might be effective in BALB/c mice. Therefore, the use of a rationally optimized combination therapy might lead to better results than monotherapy, however, clinical trials are needed for human consumption.

Surgical site infection (SSI) following spine surgery is a dreaded complication with significant morbidity and economic burden. SSIs following spine surgery can be superficial, characterized by obvious wound drainage, or deep-seated with a healed wound. Staphylococcus aureus remains the principal causal agent. There are certain pre-operative risk factors that increase the risk of SSI, mainly diabetes, smoking, steroids, and peri-operative transfusions. Additionally, intra-operative risk factors include surgical invasiveness, type of fusion, implant use, and traditional instead of minimally invasive approach. A high level of suspicion is crucial to attaining an early definitive diagnosis and initiating appropriate management. The most common presenting symptom is back pain, usually manifesting 2 to 4 weeks and up to 3 months after a spinal procedure. Scheduling a follow-up visit between weeks 2 to 4 after surgery is therefore necessary for early detection. Inflammatory markers are important diagnostic tools, and comparing pre-operative with post-operative levels should be done when suspecting SSIs following spine surgery. Particularly, Serum Amyloid A (SAA) is a novel inflammatory marker that can expedite the diagnosis of SSIs. Magnetic resonance imaging remains the diagnostic modality of choice when suspecting a SSI following spine surgery. While 18F-fluorodeoxyglucose-positron emission tomography is not widely used, it may be useful in challenging cases. Despite their low yield, blood cultures should be collected before initiating antibiotic therapy. Samples from wound drainage should be sent for Gram stain and cultures. When there is a high clinical suspicion of SSI and in the absence of superficial wound drainage, CT guided aspiration of paraspinal collections is warranted. Unless the patient is hemodynamically compromised, antibiotics should be deferred until proper specimens for culture are secured.