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Biomedical subjects

Oren Zimhony

Publications and source records attributed to Oren Zimhony.

15 recordsLinked to original sources

Pyrazinoic acid and its n-propyl ester inhibit fatty acid synthase type I in replicating tubercle bacilli.

The activity of different analogs of pyrazinamide on Mycobacterium tuberculosis fatty acid synthase type I (FASI) in replicating bacilli was studied. Palmitic acid biosynthesis was diminished by 96% in bacilli treated with n-propyl pyrazinoate, 94% in bacilli treated with 5-chloro-pyrazinamide, and 97% in bacilli treated with pyrazinoic acid, the pharmacologically active agent of pyrazinamide. We conclude that the minimal structure of pyrazine ring with an acyl group is sufficient for FASI inhibition and antimycobacterial activity.

Bacterial Proteins↗

Endocarditis caused by extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae: emergence of resistance to ciprofloxacin and piperacillin-tazobactam during treatment despite initial susceptibility.

Three episodes of bacteremia occurred in the course of prosthetic valve endocarditis caused by an extended-spectrum-beta-lactamase (ESBL)-producing Klebsiella pneumoniae strain. The second isolate developed resistance to ciprofloxacin and the third isolate to piperacillin-tazobactam (PIP-TZ) following sequential therapy with each agent. The first isolate was resistant to PIP-TZ only at high inocula, the second isolate acquired increased transcription of the acrA gene, and the third isolate became resistant to PIP-TZ due to loss of beta-lactamase inhibition by TZ. We question if and how PIP-TZ susceptibility should be reported for ESBL-producing Enterobacteriaceae.

Ciprofloxacin↗

Aspergillus peritonitis in a lupus patient on chronic peritoneal dialysis.

A woman on continuous ambulatory peritoneal dialysis (CAPD) due to renal failure in systemic lupus erythematosus (SLE) developed fungal peritonitis and survived following treatment with amphotericin B and removal of the dialysis catheter. The causative organism, Aspergillus fumigatus is very rare in fungal peritonitis and may be related in this case to the combination of SLE, end-stage renal disease (ESRD) and their treatment.

Amphotericin B↗

A "fishy remedy": an unusual transmission of Vibrio vulnificus infection.

This case report describes a unique transmission of Vibrio vulnificus infection. A 38-year-old woman with recurrent cellulitis and chronic ulcer on her leg developed necrotizing cellulitis and sepsis caused by V. vulnificus. Meticulous history investigation revealed the link to contaminated fish blood that had been applied on the ulcer by a traditional healer. Through this case, it may be stressed that a traditional remedy can sometimes be harmful and life-threatening.

Adult↗

Characterization of Mycobacterium smegmatis expressing the Mycobacterium tuberculosis fatty acid synthase I (fas1) gene.

Unlike most other bacteria, mycobacteria make fatty acids with the multidomain enzyme eukaryote-like fatty acid synthase I (FASI). Previous studies have demonstrated that the tuberculosis drug pyrazinamide and 5-chloro-pyrazinamide target FASI activity. Biochemical studies have revealed that in addition to C(16:0), Mycobacterium tuberculosis FASI synthesizes C(26:0) fatty acid, while the Mycobacterium smegmatis enzyme makes C(24:0) fatty acid. In order to express M. tuberculosis FASI in a rapidly growing Mycobacterium and to characterize the M. tuberculosis FASI in vivo, we constructed an M. smegmatis Deltafas1 strain which contained the M. tuberculosis fas1 homologue. The M. smegmatis Deltafas1 (attB::M. tuberculosis fas1) strain grew more slowly than the parental M. smegmatis strain and was more susceptible to 5-chloro-pyrazinamide. Surprisingly, while the M. smegmatis Deltafas1 (attB::M. tuberculosis fas1) strain produced C(26:0), it predominantly produced C(24:0). These results suggest that the fatty acid elongation that produces C(24:0) or C(26:0) in vivo is due to a complex interaction among FASI, FabH, and FASII and possibly other systems and is not solely due to FASI elongation, as previously suggested by in vitro studies.

Bacterial Proteins↗

Bartonella koehlerae, a new cat-associated agent of culture-negative human endocarditis.

Bartonella koehlerae is reported for the first time to be a human pathogen that causes culture-negative endocarditis. It is also shown that this species, isolated twice before from domestic cats, can be recovered as well from a stray cat population in Israel. This work follows a recent report of the same case in which the causative agent was misidentified as B. henselae, based on serology and PCR-restriction fragment length polymorphism (RFLP) analysis (A. Schattner, O. Zimhony, B. Avidor, and M. Gilad, Lancet 361:1786, 2003). B. koehlerae was identified in the valvular tissue of an endocarditis patient by DNA sequencing of the PCR products of two Bartonella genes: the genes for citrate synthase (gltA) and riboflavin synthase (ribC). The commonly used PCR-RFLP analysis of the TaqI-digested gltA PCR product did not distinguish between B. koehlerae and B. quintana or between B. elizabethae and B. clarridgeiae. PmlI digestion of the gltA amplification product failed to differentiate between B. quintana, B. clarridgeiae, and B. elizabethae. RFLP analysis of the heat shock protein (htrA) gene by TaqI digestion misidentified B. koehlerae as B. henselae. However, RFLP analysis of the ribC PCR product, digested with TaqI, was able to distinguish between the human endocarditis-associated Bartonella species tested, B. henselae, B. quintana, B. elizabethae, and B. koehlerae, as well as between the cat-associated Bartonella species, B. henselae and B. clarridgeiae. Given the expanding number of Bartonella species emerging as human pathogens, it is suggested that PCR-RFLP analysis for the diagnosis of Bartonella infections target several genes and be coupled with DNA sequencing to avoid species identification.

Bartonella↗

Enteroviruses and sudden deafness.

A young, healthy man presented with sudden severe sensorineural hearing loss and tinnitus. The results of the workup and neuroimaging were normal, as were the auditory brain stem responses. Methylprednisolone pulse therapy was associated with significant hearing improvement within 10 days. A history of a short self-limited febrile illness preceding admission (with headache, photophobia, myalgia and fatigue), a raised serum C-reactive protein level and transient leukopenia suggested an infectious cause. Lumbar puncture revealed a mononuclear pleocytosis of the cerebrospinal fluid, with negative cultures but positive polymerase chain reaction test results for enterovirus, which was later cultured from the patient's stool. The patient's wife and baby had had a similar febrile illness without hearing loss 10 days earlier, and an outbreak of enterovirus meningitis was identified in the area, which was associated with familial clustering and echovirus serotype 4 infection. The varied causes of sudden sensorineural hearing loss, which should include enterovirus, are reviewed here.

Adult↗

Treatment of Clostridium difficile-associated diarrhea.

OBJECTIVE: To review the literature related to the treatment and infection control of Clostridium difficile-associated diarrhea (CDAD). DATA SOURCES: A MEDLINE search (1966-August 2001) of the English literature was conducted. DATA SYNTHESIS: C. difficile is a leading cause of antibiotic-related diarrhea. The clinical spectrum extends from simple diarrhea to fulminant colitis. Cessation of antibiotic therapy alone is sufficient for mild cases; however, the majority of cases require oral metronidazole as the drug of choice. Vancomycin orally is reserved for patients who have failed to respond to metronidazole, are pregnant, or are severely ill. There is an important role for infection control interventions. CONCLUSIONS: CDAD is a common infection. Appropriate antibiotic treatment and infection control policies can prevent the spread and reduce the morbidity associated with this disease.

Anti-Bacterial Agents↗