Dalbavancin and Selected Comparison Agents Tested Against Indicated Gram-positive Isolates in European Medical Centers (Italy): Results from the DECIDE Program

tetracycline (96.4%) and gentamicin (99.3%). Staphylococci included MRSA (35.7%) and MR-CoNS (68.4%); and MRSA isolates were resistant to levofloxacin (96%) and erythromycin (74%). All clindamycin-susceptible SA had inducible resistance. Dalbavancin (MIC90; 0.047mg/L) was 10-fold more potent than vancomycin (MIC90; 0.5mg/L) against BHS. Erythromycin susceptibility was 82% with a 25% inducible clindamycin resistance. Conclusions: The DECIDE study demonstrated in UK and Ireland that dalbavancin has excellent activity and was more potent when directly compared to vancomycin. Dalbavancin was active against all MRSA, although the current susceptibility profiles for other antimicrobial classes tested were of great concern, particularly inducible clindamycin resistance (100%). Monitoring dalbavancin activity should be continued as this newer long-acting agent is introduced into EU clinical practice

Persistent Organic Pollutants and Mercury in Genetically Identified Inner Estuary Bottlenose Dolphin (Tursiops truncatus) Residents of the Guayaquil Gulf, Ecuador: Ecotoxicological Science in Support of Pollutant Management and Cetacean Conservation

The bottlenose dolphin is one of the most common cetaceans found in the coastal waters, estuaries, and mangroves of Ecuador. However, its population size is gradually declining in the Gulf of Guayaquil, and anthropogenic factors including habitat degradation, uncontrolled dolphin watching, dredging activities, increasing maritime traffic, underwater noise, bycatch, and marine pollution have been implicated in their decline. Very little is known about contamination by persistent organic pollutants (POPs) and mercury in bottlenose dolphins from the Pacific coast of South America. To address this research gap, the first assessment of total mercury (THg) and POPs, including polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs), in free-ranging bottlenose dolphins in mangroves (El Morro Mangrove Wildlife Refuge) of the Gulf of Guayaquil, was conducted in Ecuador in 2018. Dolphin samples (i.e., skin and blubber; n = 9), were obtained using dart biopsy field methods for contaminant analysis. POP concentrations ranged from 0.56 to 13.0 mg/kg in lipid weight, while THg ranged from 1.92 to 3.63 mg/kg in dry weight. The predominant POPs were OCPs (50% of ΣPOP), followed by PCBs (46%) and PBDEs (6.0%); particularly, p,p′-DDE, the main DDT metabolite and a potent anti-androgenic, accounting for 42% of ΣPOP, ranging from 0.12 to ∼7.0 mg/kg lw, followed by PCB 153 (8.0%) and PCB 180 (5.0%). PBDE 47 accounted for 2.0% of ΣPOP. While the POP concentrations are lower than those found in dolphins from many other regions of the world, some of the THg concentrations are within the concentration range found in dolphins from the southeastern coast of the United States. The ecotoxicological risk assessment showed that some of the sampled dolphins are exposed to immunotoxic and endocrine disruption effects by POPs and mercury. The low genetic diversity of this distinctive dolphin population, likely exhibiting genetic isolation and a unique evolutionary heritage, could be lost if the population continues to decline in the face of anthropogenic threats, including chemical pollution. Our finding shows that bottlenose dolphins in coastal Ecuador are exposed to environmental contaminants and can be used as sentinel species for ecosystem health to monitor pollution in the region and to support ecotoxicological risk assessment and regional pollutant management

Termoreverzibilni mukoadhezivni in situ hidrogel za oftalmičku primjenu: dizajniranje i optimizacija koristeći kombinaciju polimera

The purpose of the study was to develop an optimized thermoreversible in situ gelling ophthalmic drug delivery system based on Pluronic F 127, containing moxifloxacin hydrochloride as a model drug. A 32 full factorial design was employed with two polymers Pluronic F 68 and Gelrite as independent variables used in combination with Pluronic F 127. Gelation temperature, gel strength, bioadhesion force, viscosity and in vitro drug release after 1 and 10 h were selected as dependent variables. Pluronic F 68 loading with Pluronic F 127 was found to have a significant effect on gelation temperature of the formulation and to be of importance for gel formation at temperatures 3336 ºC. Gelrite loading showed a positive effect on bioadhesion force and gel strength and was also found helpful in controling the release rate of the drug. The quadratic mathematical model developed is applicable to predicting formulations with desired gelation temperature, gel strength, bioadhesion force and drug release properties.Cilj rada bio je razvoj i optimizacija termoreverzibilnog sustava za isporuku lijekova koji gelira in situ. Sustav je napravljen na bazi Pluronic F 127, a sadrži moksifloksacin hidroklorid kao modelni lijek. U radu je primjenjeno 32 potpuno faktorijsko dizajniranje s dva polimera, Pluronic F 68 i Gelrite kao nezavisnim varijablama koji su kombinirani s Pluronic F 127. Kao zavisne varijable odabrane su temperatura geliranja, čvrstoća gela, jačina bioadhezije, viskoznost i in vitro oslobađanje lijeka nakon 1 i 10 h. Pronađeno je da Pluronic F 68 u kombinaciji s Pluronic F 127 ima značajan učinak na temperaturu geliranja u rasponu od 33 do 36 C. S druge strane, Gelrite ima povoljan učinak na jačinu bioadhezije, čvrstoću gela i oslobađanje lijeka. Razvijen je kvadratni matematički model pomoću kojeg se može predvidjeti temperatura geliranja, čvrstoća gela, jačina bioadhezije i oslobađanje ljekovite tvari

Risk of surgical site infection and efficacy of antibiotic prophylaxis: a cohort study of appendectomy patients in Thailand

BACKGROUND: No data currently exist about use of antibiotics to prevent surgical site infections (SSI) among patients undergoing appendectomy in Thailand. We therefore examined risk factors, use, and efficacy of prophylactic antibiotics for surgical site infection SSI among patients with uncomplicated open appendectomy. METHODS: From July 1, 2003 to June 30, 2004 we conducted a prospective cohort study in eight hospitals in Thailand. We used the National Nosocomial Infection Surveillance (NNIS) system criteria to identify SSI associated with appendectomy. We used logistic regression analysis to obtain relative risk estimates for predictors of SSI. RESULTS: Among 2139 appendectomy patients, we identified 26 SSIs, yielding a SSI rate of 1.2 infections/100 operations. Ninety-two percent of all patients (95% CI, 91.0–93.3) received antibiotic prophylaxis. Metronidazole and gentamicin were the two most common antibiotic agents, with a combined single dose administered in 39% of cases. In 54% of cases, antibiotic prophylaxis was administered for one day. We found that a prolonged duration of operation was significantly associated with an increased SSI risk. Antibiotic prophylaxis was significantly associated with a decreased risk of SSI regardless of whether the antibiotic was administered preoperatively or intraoperatively. Compared with no antibiotic prophylaxis, SSI relative risks for combined single-dose of metronidazole and gentamicin, one-day prophylaxis, and multiple-day antibiotic prophylaxis were 0.28 (0.09–0.90), 0.30 (0.11–0.88) and 0.32 (0.10–0.98), respectively. CONCLUSION: Single-dose combination of metronidazole and gentamicin seems sufficient to reduce SSIs in uncomplicated appendicitis patients despite whether the antibiotic was administered preoperatively or intraoperatively

Daptomycin antimicrobial activity tested against methicillin-resistant staphylococci and vancomycin-resistant enterococci isolated in European medical centers (2005)

BACKGROUND: Daptomycin is a cyclic lipopeptide with potent activity and broad spectrum against Gram-positive bacteria currently used for the treatment of complicated skin and skin structure infections and bacteremia, including right sided endocarditis. We evaluated the in vitro activity of this compound and selected comparator agents tested against clinical strains of staphylococci and enterococci collected in European medical centers in 2005. METHODS: A total of 4,640 strains from 23 medical centers located in 10 European countries, Turkey and Israel (SENTRY Program platform) were tested for susceptibility by reference broth microdilution methods according to Clinical and Laboratory Standards Institute guidelines and interpretative criteria. Mueller-Hinton broth was supplemented to 50 mg/L Ca(++ )for testing daptomycin. Results for oxacillin (methicillin)-resistant staphylococci and vancomycin-resistant enterococci were analyzed separately. RESULTS: Oxacillin resistance rates among Staphylococcus aureus varied from 2.1% in Sweden to 42.5% in the United Kingdom (UK) and 54.7% in Ireland (29.1% overall), while vancomycin resistance rates varied from 0.0% in France, Sweden and Switzerland to 66.7% in the UK and 71.4% in Ireland among Enterococcus faecium (17.9% overall). All S. aureus strains were inhibited at daptomycin MIC of 1 mg/L (MIC(50/90), 0.25/0.5 mg/L; 100.0% susceptible) and only one coagulase-negative staphylococci strain (0.1%) showed an elevated (>1 mg/L) daptomycin MIC value (4 mg/L). Among E. faecalis (MIC(50/90), 0.5/1 mg/L; 100% susceptible) the highest daptomycin MIC value was 2 mg/L; while among E. faecium (MIC(50/90), 2/4 mg/L; 100% susceptible) the highest MIC result was 4 mg/L. CONCLUSION: Daptomycin showed excellent in vitro activity against staphylococci and enterococci collected in European medical centers in 2005 and resistance to oxacillin, vancomycin or quinupristin/dalfopristin did not compromise its activity overall against these pathogens. Based on these results and those of previous publications, daptomycin appears to be an excellent therapeutic option for serious infections caused by oxacillin-resistant staphylococci and vancomycin-resistant enterococci in Europe

Real-Life Evidence for Tedizolid Phosphate in the Treatment of Cellulitis and Wound Infections: A Case Series

Introduction Tedizolid phosphate 200 mg, once daily for 6 days, has recently been approved for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSIs) in several countries; however, clinical experience in real-life settings is currently limited. Here, we report on the use of tedizolid with an extended treatment duration for complex and severe ABSSSIs in real-world clinical settings. Methods Two patients with cellulitis and two patients with surgical site infection (SSI), aged 26–60 years, were treated with tedizolid phosphate 200 mg, intravenous/oral (IV/PO) or IV only, once daily at four different institutions. Results Two morbidly obese patients had non-necrotizing, non-purulent severe cellulitis, which were complicated by sepsis or systemic inflammatory response syndrome plus myositis. One female patient failed on first-line empiric therapy with IV cefalotin, clindamycin and imipenem (3–4 days), and was switched to IV/PO tedizolid (7 + 5 days). One male patient received IV clindamycin plus IV/PO tedizolid (5 + 5 days), but clindamycin was discontinued on Day 3 due to an adverse event. For both patients, clinical signs and symptoms improved within 72 h, and laboratory results were normalized by Days 7 and 8, respectively. Two other patients (one obese, diabetic female with chronic hepatitis and chronic obstructive pulmonary disease) had complicated SSIs occurring 10 days after hernia repair with mesh or 3 months after spinal fusion surgery with metal implant. First patient with previous methicillin-resistant Staphylococcus aureus (MRSA) bacteremia received a 7-day tedizolid IV course empirically. The second patient with culture-confirmed MRSA infection received a 14-day IV course. Both patients responded within 72 h, and local and systemic signs normalized by end of treatment. There were no reports of thrombocytopenia. Conclusion Tedizolid phosphate 200 mg for 7–14 days was a favored treatment option for patients with severe/complex ABSSSIs, and was effective following previous treatment failure or in late-onset infections