Occurrence of multiple drug-resistant Shiga toxigenic Escherichia coli in raw milk samples collected from retail outlets in South India.

The prevalence of Shiga-toxigenic E. coli (STEC), harbouring multidrug-resistant genes in raw milk collected from household vendors and cooperative milk marketing societies in Ernakulam District, Kerala, India, has been investigated. A higher prevalence of STEC pathotypes, with 47.16% (20 out of 42 samples), was observed in raw milk. A total of 157 STEC isolates were identified, which included notorious pathoserotypes, E. coli O157 group (10.19%) and E. coli non-O157 group 5.73%). All of the tested STEC isolates were multidrug-resistant and showed resistance to at least six different antibiotics. Two of the isolates showed resistance to 14 different antibiotics tested. Cent percentage resistance was observed for Penicillin, Cefalexine, Rifampicin, Methicillin, and Novobiocin. We observed in phenotypic assays that 26.75% of STEC isolates are ESBL producers. The bla TEM gene, a characteristic marker for ESBL production, was detected in 42.85% of the isolates. The study points out the risk of virulent and multidrug-resistant STEC in raw milk and the need for stringent quality surveillance and assurance plans to alleviate the potential public health threat. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-021-05226-x.

Recent Advances in the Chemistry of Pentafulvenes.

Pentafulvenes are a unique class of compounds that originally attracted attention due to their propensity to display nonbenzenoid aromaticity. Subsequently, they were recognized as valuable synthons for the construction of a wide range of compounds by virtue of their ability to display multiple cycloaddition profiles. Naturally, this area of organic chemistry has experienced rapid growth over the last five decades, fueled by elegant work showcasing the unique reactivity of pentafulvenes in a plethora of cycloaddition reactions. In this Review, we have attempted to provide a systematic account of the methods for the generation of pentafulvenes, their rich and varied cycloaddition chemistry, organometallic reactions, and theoretical studies that support their versatility. Further, we have highlighted their applications in the synthesis of a variety of complex structural frameworks. It is our conviction that this Review will be useful to a wide range of chemists, and will spur further research in this promising area.

(+)-Camphor-mediated kinetic resolution of allylalanes: a strategy towards enantio-enriched cyclohex-2-en-1-ylalane.

An efficient (+)-camphor-mediated kinetic resolution of racemic cyclohex-2-en-1-ylalane is described. This approach provides an enantiomerically enriched form of the alane, in situ available for synthetic uses. Applied to the allylation of aldehydes, this protocol leads to the corresponding homoallylalcohols in a highly enantioselective manner.

Titanium and Zirconium Hydride-Catalyzed Regioselective Isomerization of 1,4-Dihydrofulvenes: Access to 1-Substituted 1,2-Dihydrofulvenes.

Zirconium hydride-catalyzed C═C double bond migration from nonconjugated to conjugated dienes is described. Applied to 1-substituted 1,4-dihydrofulvenes, the migration leads selectively to 1-substituted 1,2-dihydrofulvenes. The C═C double bond migration can also be catalyzed by titanium hydride, allowing a one-pot procedure to provide 1-substituted 1,2-dihydrofulvenes from pentafulvenes via two titanium-catalyzed steps. This sequence was proven to be temperature-dependent, allowing the selective access to a conjugated or nonconjugated adduct by a simple temperature tuning. The synthetic potential of the methodology was illustrated by the diastereoselective synthesis of a polyhydroxycyclopentane.

Titanium-catalyzed hydroalumination of conjugated dienes: access to fulvene-derived allylaluminium reagents and their diastereoselective reactions with carbonyl compounds.

The described titanium-catalyzed hydroalumination of conjugated dienes opens up a new way to allylaluminium reagents. The reaction is carried out by using diisobutylaluminium hydride (DIBAL-H) and a catalytic amount of [Cp2TiCl2] (Cp = cyclopentadienyl). When applied to mono- and disubstitued pentafulvenes, this reaction proceeds in a highly endocyclic manner. The formed allylaluminium compounds react regio- and stereoselectively with both aldehydes and ketones to afford homoallylic alcohols that are suitable synthons for functionalized cyclopentanones. An extension of this methodology to simple dienes was also investigated. In the proposed mechanism, the initially formed bimetallic species (Ti/Al) are involved in the two possible catalytic cycles with a direct hydroalumination or/and a hydrotitanation followed by a titanium to aluminium transmetallation.

Pentafulvene-derived η3-allyltitanocenes as intermediates for the stereoselective functionalization of 5-membered carbocycles.

Allyltitanocene complexes can be generated by reacting pentafulvenes with DIBAL-H and Cp2TiCl2. Their coupling with aldehydes affords homoallylic alcohols in a highly regio- and stereoselective manner. The potential of this method for the stereoselective synthesis of cyclopentane derivatives is illustrated.

Anidulafungin: a drug evaluation of a new echinocandin.

BACKGROUND: Over the past two decades, the frequency and type of invasive fungal infections have increased greatly and thus have driven the need for new antifungal agents. Anidulafungin is the newest addition to the echinocandin armamentarium. OBJECTIVE: The intention of this review is to provide a drug evaluation of anidulafungin, including its spectrum of activity, pharmacokinetics, pharmacodynamics, clinical efficacy, adverse event profile, and its role in the treatment of invasive candidiasis. METHODS: A PubMed search was performed to gather the most current and pertinent articles. CONCLUSIONS: Clinical trials have demonstrated anidulafungin's efficacy and tolerability in invasive candidiasis. Anidulafungin is not associated with any drug-drug interactions and does not require dosage adjustment in patients with renal and/or hepatic impairment.

Cephalosporin-induced leukopenia following rechallenge with cefoxitin.

OBJECTIVE: To describe a case of cefazolin-induced leukopenia in a critically ill patient who developed this adverse reaction upon rechallenge with cefoxitin. CASE SUMMARY: A 22-year-old male was admitted after a motor vehicle crash. beta-Lactam therapy was initiated with vancomycin, cefepime, and metronidazole and, upon identification of methicillin-sensitive Staphylococcus aureus bacteremia 4 days later, therapy was narrowed to cefazolin 1 g every 12 hours. The dose was adjusted to 1 g every 12 hours during continuous venovenous hemodialysis. Imipenem was given for 2 days, resulting in a total of 18 days of beta-lactam treatment, at which time he developed significant leukopenia (white blood cell [WBC] count 0.9 x 10(3)/microL). Antimicrobial treatment was changed to tigecycline and continued for suspected pleural space infection. The patient's WBC count recovered within 4 days after the change in therapy. He was taken to surgery 8 days after cefazolin was discontinued and received perioperative prophylaxis with cefoxitin (total dose 3 g). Subsequently, the patient again became severely leukopenic (WBC count 2.4 x 10(3)/microL). Within a week after surgery, the patient developed septic shock secondary to multidrug-resistant Escherichia coli bacteremia and died. DISCUSSION: beta-Lactam-induced leukopenia is a rare but well-described adverse drug reaction. It is a cumulative dose-dependent phenomenon reported to occur most often after 2 weeks of therapy. The mechanism of leukopenia is thought to be secondary to either an immune-mediated response or direct bone marrow toxicity. Rechallenge with a different beta-lactam antibiotic has not been shown to consistently cause recurrent leukopenia. The case described here suggests an immune-related mechanism for the development of leukopenia. Use of the Naranjo probability scale determined the association between cephalosporin use and leukopenia to be probable. CONCLUSIONS: Cefazolin was a probable cause of this patient's leukopenia. It is important for clinicians to recognize beta-lactam-induced leukopenia and maybe recommend use of a drug from a different antibiotic class if continued treatment is indicated.

The role of carbapenems in the treatment of severe nosocomial respiratory tract infections.

The prevalence of antibiotic-resistant bacteria continues to increase, particularly in patients in the intensive care unit with nosocomial pneumonia. The intention of this review is to provide an overview of severe nosocomial pneumonia, carbapenems and the problem of bacterial resistance to antimicrobial agents. Attention was focused on the efficacy, safety and pharmacodynamics of imipenem, meropenem, ertapenem and doripenem. Issues on the impact of appropriate empiric antibiotic therapy for nosocomial pneumonia patients considered at risk for resistant pathogens are discussed. Critical decision making regarding the use of carbapenems for treating severe nosocomial pneumonia requires careful consideration of the four Ds of optimal antimicrobial therapy: right Drug, right Dose, De-escalated to pathogen-directed therapy and right Duration of therapy.

Micafungin: a new echinocandin antifungal.

The echinocandins represent the newest class of antifungals to combat infections caused by Candida sp. Micafungin is an echinocandin recently approved by the United States Food and Drug Administration. It is indicated in adults for esophageal candidiasis and prophylaxis against candidal infections in hematopoietic stem cell transplant recipients. Micafungin exhibits in vitro fungicidal activity against Candida sp, including fluconazole-resistant isolates. Its in vivo efficacy is comparable to that of fluconazole in the treatment of esophageal candidiasis and superior to that of fluconazole for prophylaxis of invasive candidal infections. Because it is not significantly metabolized by the cytochrome P450 3A system, micafungin is associated with few drug interactions. Micafungin does not require adjustment in patients with renal and/or hepatic impairment, and it has been shown to be well tolerated in both adult and pediatric patients. Its efficacy against Candida sp, coupled with its overall safety and drug interaction profiles, makes it an attractive option in the treatment against esophageal candidiasis and prophylaxis against invasive candidal infections.