hi i posted two weeks ago regarding pan resistant VRSA case that ended in patient death and NCDC involvement, unfortunately i have second patient.
we have admitted a second patient today presenting with confirmed VRSA bacteremia. I felt very scared after preliminary susceptibility result came back because profile is identical.
vancomycin, linezolid resistant, daptomycin non-susceptible and ceftaroline non responsive. we have not completed full panel but based on the first patient I am unoptimistic about telavancin, teicoplanin, or TMP-SMX combinations. reference lab has been contacted immediately and NCDC have been notified, they are treating as a priority escalation given the prior case.
clinical picture on admission:
patient is febrile, hemodynamically unstable, bacteremic on first draw. no confirmed endocarditis yet and TEE is being arranged. early signs of encephalopathy, no osteomyelitis confirmed yet but we are scanning aggressively because of how first case progressed. source appears again to be line-associated, but are not anchoring on that, VHF containment protocols are in place. discovered current patient works at same vancomycin hydrochloride manufacturing factory as the previous patient.
have formally reported this to NCDC and have requested an emergency occupational health and environmental investigation of factory. do not yet know whether if a point source contamination from factory environment, shared exposure to a colonised coworker, aerosolised/surface level antibiotic exposure creating selection pressure on commensal flora over time.
am concerned that factory introduces chronic low level environmental exposure to vancomycin and workers have absorbing subtherapeutic concentrations daily creating selection pressure environment within the factory and may have driven stepwise resistance acquisition in patients. we have asked whether any hospitals in mumbai or maharastra have seen unusual staph aureus resistance patterns in 18 months that may represent early or intermediate stages of phenotype.
initiated source control, all removable hardware removed and drainage of accessible collection and attempting fosfomycin combination strategy that was suggested too late in the first case, synergy testing is requested from the reference lab and have contacted AIIMS for phage therapy access but same 9 week wait
to my colleagues here who helped last time:
I recall your suggestion, fosfomycin plus vanc plus ceftaroline mechanism, quinupristin dalfopristin discussion but no longer available as have exhausted all supply from first patient and rifampin combination.
I am posting because I believe this is not a clinical question anymore and am concerned this may be an outbreak but also maybe occupational.
If you are in India and have seen anything resembling this resistance pattern in Staph aureus please comment or message me.
will update as the case develops. I hope I don't have to write third post.
Edit: patient history confirms he has worked at the facility with first patient both were in same production line handling raw vancomycin hydrochloride powder
Edit2: hi am very confused and need input.
existence of pan resistant vrsa doesn't make sense because vancomycin exposure by itself cannot produce what an seeing, as i understand vancomycin selects strongly for vanA mediated resistance, mechanism is highly specific and does not touch ribosome, so it cannot drive linezolid resistance, it does not alter membrane charge so cannot produce daptomycin non susceptibility???
they are independent cellular systems requiring entirely independent evolutionary event, we think maybe? the factory created sustained selection pressure that retained preassembled multiresistant genetic element likely plasmid or transposon carrying vanA alongside cfr or optrA for linezolid resistance in strain that already have compromised membrane phenotype then under vancomycin pressure the entire element is conserved even for genes conferring resistances vancomycin has no direct relationship to.
other possibility is that factory environment such as biofilms on production surface, coexisting enterococcal and staphylococcal colonisation on employees repeated subtherapeutic antibiotic exposure function as horizontal gene transfer incubator.
is likely we are not looking at two workers that independently evolved same phenotype under the same pressure but a preassembled strain being transmitted, harbored, or repeatedly reacquired from shared environmental reservoir
Edit 3: discovered factory also manufacture chloramphenicol on adjacent production line in same building with employees rotating lines, am suspect of vancomycin pressure driving vanA acquisition and chloramphenicol pressure coselecting and stabilizing cfr, both operating concurrently in same human hosts over years of daily exposure
Edit 4: rifampin trialed with delafloxacin as companion agent with no response as without functioning partner drug, rpoB mutations emerged. minocycline came back non susceptible on reference lab MICs, likely tet(M) or tet(K) efflux mediated with both highly mobile, likely coacquired on same element carrying other resistance determinants, given what we know about chloramphenicol line, am suspecting we have not fully characterised how many resistance genes plasmid is actually carrying.
Edit 5: hi, preliminary genomics confirmed compensatory mutations present in ddl, murF, cls and yycFG. cfr carrying plasmid is stable, conjugation competent and carrying additional uncharacterized open reading frames, have not yet matched to any registered sequence in GenBank or BV-BRC databases. vanA operon shows structural modifications beyond Tn1546 canonical architecture and growth curve analysis against reference MRSA demonstrates identical replication kinetics. low fitness cost detected under standard competition assays, organism also showing preliminary biofilm formation indices 340% above MRSA reference strain. patient creatinine is 6.8