ABSTRACT
The aim of this study was to compare the in vitro activity of delafloxacin with other fluoroquinolones against bacterial pathogens recovered from inpatients with osteomyelitis, Acute Bacterial Skin and Skin-Structure Infections (ABSSSI). In total, 100 bacterial isolates (58 % Gram-negative and 42 % Gram-positive) recovered from inpatients between January and April 2021, were reidentified at species level by MALDI-TOF MS. Antimicrobial susceptibility testing was conducted using the broth microdilution method and the detection of biofilm formation was assessed through the microtiter plate assay. The screening for mecA was carried out by PCR, while mutations in the Quinolone Resistance Determining Regions (QRDR), specifically gyrA and parC, were analyzed using PCR followed by Sanger sequencing. Results showed that delafloxacin exhibited greater in vitro potency (at least 64-times) than the other tested fluoroquinolones (levofloxacin and ciprofloxacin) when evaluating Staphylococcus aureus (MIC50 ≤0.008 mg/L) and coagulase-negative Staphylococcus (MIC50 0.06 mg/L). Furthermore, delafloxacin (MIC50 0.25 mg/L) was at least 4 times more potent than other tested fluoroquinolones (MIC50 1 mg/L) against P. aeruginosa. No difference in delafloxacin activity (MIC50 0.03 mg/L) was observed against Enterobacter cloacae when compared with ciprofloxacin (MIC50 0.03 mg/L). Despite presenting low activity against K. pneumoniae isolates (22.2 %), delafloxacin exhibited twice the activity compared to both levofloxacin and ciprofloxacin. Delafloxacin also exhibited a strong activity (71.4 %â85.7 %.) against biofilm producing bacterial pathogens tested in this study. Interestingly, 82.14 % of the staphylococci tested in this study harbored mecA gene. In addition, the gyrA and parC genes in fluoroquinolone-resistant Gram-negative isolates displayed different mutations (substitutions and deletions). Herein, we showed that delafloxacin was the most active fluoroquinolone against staphylococci (including MRSA) and P. aeruginosa when compared to other fluoroquinolones such as ciprofloxacin and levofloxacin.
ABSTRACT
BACKGROUND: Treating complicated skin and skin structure infections (cSSSIs) can be challenging. Tigecycline was compared to vancomycin/aztreonam in patients with cSSSIs in a multinational trial; this article reports on the Latin American (LA) population. METHODS: Patients were randomly assigned to receive tigecycline or vancomycin/ aztreonam. Primary endpoint was clinical cure rate at test-of-cure (TOC). Several secondary endpoints and safety were also assessed. RESULTS: A subtotal of 167 LA patients from the multinational trial (N = 573) received ≥ 1 dose of study drug. At TOC, cure rates were similar between tigecycline and vancomycin/aztreonam in the clinically evaluable population.) Noninferiority of tigecycline could not be demonstrated (insufficient sample sizes). Tigecycline-treated patients had higher incidences of nausea, vomiting, anorexia; vancomycin/aztreonam-treated patients had higher incidences of pruritus and rash. CONCLUSIONS: Efficacy results in the LA population were consistent with the multinational study suggesting that tigecycline is noninferior to vancomycin/aztreonam in treating patients with cSSSI.
INTRODUCCIÓN: El tratamiento de infecciones complicadas de piel y tejidos blandos (ICPTB) puede representar un desafío. Se comparó la eficacia de tigeciclina versus vancomicina/aztreonam en pacientes con ICPTB en un estudio multicéntrico; este artículo se refiere a la experiencia en Latinoamérica (LA). MÉTODO: Se asignaron, en forma randomizada, los pacientes a dos grupos de tratamiento: tigeciclina o vancomicina/aztreonam. La meta a evaluar (outcome) primaria fue la curación clínica, denominada test de curación (TC). Se establecieron, además, metas secundarias y la evaluación de seguridad del fármaco. RESULTADOS: Un subtotal de 167 pacientes procedentes de LA, de un estudio multinacional que incluyó 573 pacientes, recibieron ≥ 1 dosis del fármaco en estudio. Al TC, los porcentajes de curación fueron similares entre tigeciclina y vanco-micina/aztreonam en los pacientes clínicamente evaluables). La no inferioridad de tigeciclina no pudo ser demostrada (tamaño de muestra insuficiente). Los pacientes tratados con tigeciclina tuvieron mayor incidencia de náuseas, vómitos y anorexia; los pacientes que recibieron vancomicina/aztreonam tuvieron mayor incidencia de prurito y rash. CONCLUSIONES: Los resultados de eficacia en LA fueron consistentes con el estudio multinacional sugiriendo que tigeciclina no es inferior a vancomicina/aztreonam en el tratamiento de pacientes con ICPTB.