January 2019: General ID

If you’re treating P. falciparum malaria in someone coming from an area where both P. falciparum and P. vivax are present, maybe go ahead and give some primaquine.  Remember that both P. vivax and P. ovale have a hypnozoite phase (i.e. the parasites go have a quiet little party in the liver and can hang out there for months to years without producing symptoms), which is why malaria due to these organisms can result in relapsed infection far after treatment of the initial disease, and is why we treat these infections with a 14-day course of primaquine to prevent relapse.  OK, but what if your patient is coming from somewhere that has both falciparum and vivax malaria, but you only detect P. falciparum?  We know that co-infections can occur – so should you give primaquine empirically?

The authors performed a meta-analysis of studies published between 1960 and 2018 examining the efficacy of various drug regimens for uncomplicated P. falciparum malaria.  Specifically, they looked at only the studies that commented on the presence or absence of P. vivax parasitemia after treatment.  The researcher’s primary outcome of interest was the risk of post-treatment P. vivax parasitemia based on the antimalarial treatment used.

One hundred and fifty-three studies were included (total n=31,262); 85% were done in the Asia and the Pacific, 10% in the Americas, and 5% in Africa.  The risk of P. vivax parasitemia 6 weeks after treatment was higher with regimens using agents more rapidly eliminated from the body (15% for artemether-lumefantrine versus 5% each for dihydroartemisinin-piperaquine and artesunate-mefloquine).  However, while recurrent parasitemia was delayed in onset in the patients given piperaquine and mefloquine, by week 9 after treatment the rate of P. vivax parasitemia had reached 15% in all groups.  Hence, routine use of primaquine in areas where P. vivax is endemic has the potential to substantially reduce recurrent parasitemia even when P. vivax is not specifically identified. 30587297

Speaking of P. vivax, splenectomy seems to be a risk factor for malaria, and particularly vivax malaria.  In this retrospective case-control study, the authors compared all patients seen at a Papau New Guinea hospital over a 9-year period who underwent splenectomy to all patients hospitalized for some other reason; in addition, starting in 2015 they prospectively followed all patients who had splenectomy for trauma for a 14 month period.  A total 67 of 10774 patients hospitalized during the study period underwent splenectomy, and these patients had a higher rate of incident malaria in the twelve months following their admission (aHR 5.0; 95% CI 3.4-7.3; p < 0.001); this rate was higher for P. vivax (aHR 7.8; p<0.001) than P. falciparum (aHR 3.0; p<0.001).  In the prospective cohort, 11 patients underwent splenectomy, and they had a total 12 episodes of P. vivax and 6 episodes of P. falciparum in the following 14 months.  So, consider splenectomy a risk factor for malaria generally and for P. vivax specifically. 29771281

How well do patients with open reduction and internal fixation (ORIF) device infections fare when managed with implant retention? Quite well, actually – but only for infections that developed within 10 weeks of surgery.  The authors conducted a prospective observational study including all patients with ORIF infections at a single hospital over a 10-year period.  They classified the infections as early (within 2 weeks of surgery), delayed (within 3—10 weeks), and late (>10 weeks).  The standard approach to these infections at this medical center was to give 2 weeks of parenteral therapy followed by oral antimicrobials for a total of 12 weeks, ideally using a quinolone (for enterobacteriaceae) or quinolone-rifampin (for staphylococci) based regimen.

A total 229 patients were included, and the median duration of follow-up was just over 2 years.   S. aureus was the most common pathogen (found in 42%), though CONS, enterobacteriaceae, streptococci, and anaerobes were also frequently isolated.  Physicians attempted debridement and implant retention (DAIR) in 86% of early infections, 58% of delayed infections, and 10% of late infections; in these cases, the treatment failure rates were 14%, 12%, and 33% respectively.  Late infections had higher rates of treatment failure with the DAIR approach versus implant removal (33% vs 11%; p=0.05); when DAIR was attempted in late infections, use of rifampin was associated with lower rates of failure (8% vs 50%; p<0.01).

So, ORIF infections seem to behave more or less like prosthetic joint infection (PJI): the prospect for cure with antibiotics and implant retention is great in early infections and not-so-great in late infections, and if you are going to try to salvage a late infection you had better hope the organism is sensitive to rifampin. 29649599

While we’re on the topic of orthopedic infections, a retrospective cohort study published this month examined the effect of preoperative oral antibiotic use in the preceding 3 months on rates of PJI after knee or hip arthroplasty.  Over an 11-year period, 23,171 patients underwent arthroplasty at a single university medical center in Finland, of whom 158 (0.7%) developed PJI.  Preoperative antibiotic use emerged as a protective factor for PJI in a multivariate model (OR 0.4, 95% CI 0.22-0.73), an association that persisted after propensity score matching (OR 0.34, 95% 0.18-0.65).  The authors rightly point out that routine use of preoperative antibiotics in primary arthroplasty is unreasonable (that’s a huge degree of antibiotic exposure just to push the PJI rate down from 0.7% to 0.3%), but perhaps it would be a reasonable approach for some select group of patients at extremely high risk for PJI. 30625412

ID doctors are all over the place when it comes to the treatment of S.aureus bacteremia (SAB).  This should be more surprising than it is. Doesn’t SAB make up a good 10-20% of our consults?  Doesn’t our professional society have a clinical guideline for managing MRSA infections? 

The authors engaged with the Emerging Infection Network (EIN) listserv, an online group of ID docs that includes mostly US and Canadian practitioners and serves a “consult club” for sharing challenging cases.  Researchers gave the EIN members a 11-item multiple choice survey about their management of SAB, distributed by email with two reminders, then reviewed the results. Of EIN’s 1286 members, 723 (56%) responded to the survey; compared to the non-responders, responders were more likely to have >25 years of ID experiences (30% vs 21%; p<0.001); otherwise, the groups were similar.  

Most ID doctors indicated they routinely obtain repeat blood cultures (92%) and an echocardiogram (75%), whereas <5% each indicated they routinely obtain spinal MRIs, CT scans of the abdomen and pelvis, or dilated eye exams.  Of those who obtain echocardiograms, about a fifth obtain a transesophageal echo (TEE) in every case, whereas the majority (71%) only obtain a TEE under select clinical circumstances.  Most ID docs considered persistent bacteremia (86%) and lack of clinical improvement (81%) as appropriate indications for a TEE; no other factors were supported by a majority of respondents.  Practitioners in the American Midwest, Northeast, and South were more likely to always order a TEE than practitioners in other regions.

When treating MSSA bacteremia, the respondents were equally split between preferring nafcillin, preferring cefazolin, and not having a strong preference between the two.  The most common rationales were what you’d expect (cefazolin: cost and safety; nafcillin: inoculum effect, “gold standard”), and ID docs with >15 versus <15 years of experience were more likely to use nafcillin than cefazolin (37% vs 26%; p=0.048).  When treating MRSA bacteremia with a vancomycin MIC of 2, a majority of respondents (51%) suggested continuing vancomycin so long as the patient is clinically improving; of those who would switch therapy, most (76%) preferred daptomycin.  A majority of respondents (75%) recommended switching therapy at day 6 of persistent bacteremia on vancomycin; of these, those who would change to monotherapy and those who would change to combination therapy were about evenly split, and again daptomycin was the overwhelmingly favored alternate therapy.  Interestingly, combination antibiotic therapy, and specifically the combination of daptomycin and ceftaroline, was more likely to be used by docs in the Northeast and West than by docs in other regions (15% vs 5%; p=0.004).  When choosing daptomycin, respondents from the Northeast and West were also more likely than their peers elsewhere to recommend higher doses (10-12mg/kg vs 6-8 mg/kg daily). 

As for total duration of therapy, 73% of ID docs indicated they would treat an uncomplicated MRSA bacteremia with 14 days of IV antibiotics, whereas 13% were willing to transition to oral antibiotics to complete a 14 day course; minorities indicated they would treat for a week or less (4%) or 3-4 weeks (7%), respectively.  Opinions regarding the duration of therapy for septic thrombophlebitis proved more variable, with 25% of respondents recommending 6 weeks, 52% recommending 4 weeks, and 19% recommending 2 weeks of antibiotics.

A randomized control trial of so many differences in management is probably infeasible, bur this degree of variability in practice seems ripe for a multicenter cohort study of S. aureus bacteremia.  Any takers? 30601989

Infectious zika virus can persist in semen for over a month after acute infection.  I don’t have much to say about this article, but felt it was important to guide ID clinician’s recommendations regarding abstinence after Zika virus infection to prevent Zika virus transmission.  Zika virus infection is known to be sexually transmitted, and previous recommendations about abstinence to prevent sexual transmission have been based on detectable levels of Zika in serum and semen.  However, viral RNA is often detectable in the host long after the disappearance of infectious particles; hence, the authors sought to determine the frequency and duration of infection virus isolation in semen in men infected with Zika.

The authors conducted a prospective cohort study of patients with Zika virus infection in Puerto Rico.  Active surveillance of patients presenting to a hospital and its clinic with an acute febrile illness captured all patients enrolled in the study.  The researchers used observation of cytopathic effect, increase in viral RNA, and flow cytometry to determine whether cell cultures became infected with Zika virus from clinical samples.  Thirty-two patients submitted semen specimens; researchers were able to isolate infectious Zika virus from a total 8 of 78 specimens (10% of the submitted samples; 25% of participants).  Virus was isolated at only one time point in each case.  Infectious Zika virus was isolated in samples collected between 15 and 38 days after the onset of symptoms; notably, all but one specimen was collected within 30 days.  So, it seems reasonable to expect that a 60-90 day period of abstinence after the onset of Zika symptoms would be adequate to prevent sexual transmission of the virus.  30059980

When might we consider treating osteomyelitis with less than four weeks of therapy?  In light of OVIVA’s publication, I want to point out a meta-analysis on the duration of antimicrobial therapy for osteomyelitis published in the International Journal of Antimicrobial Agents this month.  The authors reviewed PubMed and Embase for RTCs, cohort studies, and case-control studies comparing antibiotic durations for osteomyelitis, comparing short course therapy (less than 4-6 weeks) to standard durations.  A total 15 studies (5 RTCs and 10 observational studies, total N=3598) were included in the meta-analysis.  Short course therapy was associated with treatment failure (OR 1.5; 95% CI 0.97-2.34), primarily driven by increased rates of failure in vertebral osteomyelitis (OR 2.1 95% 1.18-3.57); in contrast, short duration of antibiotic treatment was not associated with treatment failure in acute osteomyelitis of childhood.  Meta-regression identified S. aureus as being associated with treatment failure in vertebral osteomyelitis.  So based on these data, less than four weeks of antibiotic treatment is not appropriate for vertebral osteomyelitis, particularly when the causative organism is S. aureus, but (pending further research) may be appropriate in other clinical settings.  30639627