Infectious Disease... PAUL SAX MD.

So what have we learned so far? Here are few items, ranging from obvious to obscure, inspired by a similar roundup last December.

• Here's a terrific review for all clinicians of contemporary hepatitis C treatment. Sofosbuvir/velpatasvir (SOF/VEL) and glecaprevir/pibrentasvir (GLE/PIB) are the best options for initial therapy — pangenotypic, highly effective (>95% cures), well tolerated. Why choose anything else? Also, most patients need minimal monitoring — test for cure 12 weeks after treatment stops and monitor for re-infection if at ongoing risk. Provided they don't have advanced liver disease (and referral to a hepatologist), that's pretty much it!
• Compared to other candida species, Candida glabrata has both more azole and echinocandin resistance. This is particularly the case in transplant and oncology centers that use extensive antifungal prophylaxis. In vitro, Candida parapsilosis also shows reduced susceptibility to echinocandins, but the clinical significance of this finding is uncertain.
• TMP/SMX is likely fine for treatment of HIV-related cerebral toxoplasmosis. Small caveat — there has never been a fully powered comparative trial versus pyrimethamine/sulfadiazine. However, there is extensive international experience with TMP/SMX, plus increasing clinical use in the U.S. since Shkreli/Turing Pharmaceuticals raised the price of pyrimethamine from $13.50 to $750 per dose.
• Asplenia or hyposplenism is an important risk factor for severe babesiosis. Others risk factors include older age (>50, ugh), receipt of cancer chemotherapy, advanced HIV disease, and treatment with TNF blockers or rituximab. The last of these is a particularly bad player in persistent infection.
• Among patients with HIV, those with poor adherence often have little or no resistance. They don't take enough of their medications to select for resistance. Further proof comes from several treatment-experienced trials of second-line therapy or beyond — baseline lack of resistance is associated with worse outcomes. Poor adherence carrying through to the second line therapy explains this apparent paradox.
• Doxycycline reduces the risk of C. diff in hospitalized patients. This is one of many reasons it remains many ID doctor's favorite antibiotic.
• In treatment-naive patients, dolutegravir plus lamivudine is non-inferior to dolutegravir plus TDF/FTC. Full results to be presented soon. This should mean that prices for HIV drugs come down — but it won't be so simple, as explained in this excellent perspective from the NEJM.
• Carbamazepine and phenobarbital induce the metabolism of dolutegravir. For phenobarbital, the effect is likely to be substantial enough to make co-administration with dolutegravir contraindicated.
• Cefiderocol is an investigational cephalosporin with activity versus highly resistant gram negative infections. This includes many carbapenem-resistant isolates. It is a novel "siderophore cephalosporin", meaning it's transported through the outer membrane of bacteria through iron transporters (at least I think that's what it means).
• Obesity and diabetes are risk factors for invasive group B strep infections. This is now a more common pathogen in older adults than it is in newborns, a fact that surprises many medical students.
• Prednisone reduces the risk of immune reconstitution inflammatory syndrome (IRIS) in patients with HIV-related TB. IRIS was diagnosed in 47% of those in the placebo arm, versus 33% in prednisone arm. There was no difference in mortality.
• Corynebacterium striatum, commonly found as part of normal skin flora, can cause clinically significant infections. Vancomycin is the preferred initial therapy, as the organism is increasingly resistant to beta-lactams and quinolones. Other options include linezolid and daptomycin, based on susceptibility testing. Device, hardware and line-related infections are most commonly reported, along with respiratory tract infections in immunocompromised hosts and patients with COPD.

Special Staph aureus section — hey, this is inpatient ID, remember?

• Oxacillin is marginally better tolerated than nafcillin. Nafcillin has more renal-related adverse effects. However, cefazolin is better tolerated than both of them — but is it as active? Let the debate rage on.
• Penicillin-susceptible Staph aureus (PSSA) can be treated with penicillin. This presumes that the laboratory has definitively concluded it's susceptible; since not all labs do this, however, the endocarditis guidelines recommend oxacillin or nafcillin for PSSA even though penicillin is more active in vitro. (We tend to use penicillin at our hospital.)
• Adjunctive rifampin does not improve outcomes in Staph aureus bacteremia. Rifampin still has a role in prosthetic valve endocarditis, as it targets bacteria in biofilms which could induce late relapse. However, there is no need to use rifampin to clear the initial bacteremia, and giving it with a high burden of infection could select for resistance.
• There is an ongoing clinical trial comparing IV to oral antibiotics in uncomplicated Staph aureusbacteremia. Called SABATO (for "Staph aureus Bacteremia Treatment Options" — clever!), the trial will enroll patients after 5-7 days of IV therapy, randomizing them to continued IV versus oral TMP/SMX. If they have sulfa allergies, MSSA patients will get clindamycin, MRSA patients will get linezolid.
• Mortality from Staph aureus pneumonia remains high. This is especially true when it's a complication of influenza. And if it's pneumonia due to MRSA, linezolid may be preferable to vancomycin.
• For surgical prophylaxis when concerned about MRSA, vancomycin alone isn't enough.Vancomycin plus cefazolin is recommended. And count this as additional evidence that vancomycin has many weaknesses.