This Week in Infectious Disease — Sep 11, 2026

Welcome to This Week in Infectious Disease. This week we're covering 10 notable papers spanning antibacterial therapy and resistance, antimicrobial and antifungal dosing decisions, and prevention — from influenza vaccines to pre-exposure prophylaxis in pregnancy. Let's dive in.

We start with two papers that speak directly to what you prescribe on the ward. In Antimicrobial Agents and Chemotherapy, Ramsamy and colleagues used the international TriNetX platform to compare cefazolin with antistaphylococcal penicillins in methicillin-susceptible Staph aureus bacteraemia [1]. From more than a hundred thousand patients with MSSA bloodstream infection, just under four thousand met their criteria, and after propensity score matching they analysed roughly two thousand patients per arm. Ninety-day all-cause mortality was about ten percent with cefazolin versus about fifteen percent with antistaphylococcal penicillins — a reduction of roughly a third in the hazard of death. C. difficile infection was also less frequent with cefazolin, about five percent versus seven percent. This is retrospective and observational, so confounding by indication and by source control almost certainly remains, and the fact that only three and a half percent of identified patients were eligible tells you the analytic cohort is highly selected. Still, it adds to a consistent body of real-world data favouring cefazolin as the workhorse for MSSA bacteraemia outside central nervous system infection. Alongside that, the BMJ published a clinical review by Long and colleagues on skin and soft tissue infections [2], which is worth keeping for reference. The practical messages are that laboratory testing adds little in most patients, that point-of-care ultrasound is genuinely useful when you cannot tell cellulitis from abscess, that drainage — not antibiotics — is the primary treatment for an abscess, and that decolonisation for recurrent disease remains controversial. Newer agents such as tedizolid, delafloxacin, omadacycline and ceftaroline are positioned as selective options, not first-line.

The second theme is Gram-negative resistance, and here two papers fit together nicely. In the International Journal of Antimicrobial Agents, Sader and colleagues report five years of surveillance — just over twelve thousand Enterobacterales from medical centres across Asia Pacific and Latin America, collected before aztreonam-avibactam entered clinical use in those regions [6]. Aztreonam-avibactam was active against essentially all isolates, and against carbapenem-resistant Enterobacterales it retained susceptibility of about 97 percent in Asia Pacific and above 99 percent in Latin America. Contrast that with ceftazidime-avibactam, meropenem-vaborbactam and imipenem-relebactam, which covered only about half to two thirds of carbapenem-resistant isolates in Latin America and under forty percent in Asia Pacific — a direct reflection of metallo-beta-lactamase predominance in Asia Pacific versus KPC predominance in Latin America. Cefiderocol covered about ninety-one percent. The clinical message is that your local carbapenemase epidemiology, not the label, should drive empiric choice. And in Antimicrobial Agents and Chemotherapy, Du and colleagues show what happens when we lean on ceftazidime-avibactam [7]. Studying thirty-five clonally related ST11 KPC-producing Klebsiella isolates from eight hospitalised patients, they found the KPC-33 variant emerging repeatedly under ceftazidime-avibactam pressure — in four of the seven treated patients, and notably also in one patient who had never received the drug. Importantly, KPC-33 did not carry a uniform fitness cost; fitness was strain-background dependent. So we should not assume these resistant variants will simply fade away once drug pressure is removed. Repeat cultures and repeat susceptibility testing during prolonged ceftazidime-avibactam therapy are warranted.

Third, dosing and drug exposure — where three papers converge on individualisation. Also in Antimicrobial Agents and Chemotherapy, Gautier-Veyret and colleagues built a multiparametric algorithm to set the initial voriconazole maintenance dose [8], drawing on nearly a thousand trough measurements in 277 patients and validating externally in a small independent cohort. The final model combined daily dose, CYP2C19 genotype, C-reactive protein, age and underlying disease, explaining roughly seventy percent of the variability in trough concentrations — though it tended to underestimate the lowest troughs and overestimate the highest, which is exactly where clinicians most need accuracy. It is a promising tool awaiting prospective evaluation, and it does not replace therapeutic drug monitoring. That pairs with a narrative review in the International Journal of Antimicrobial Agents from Zhu and colleagues on isavuconazole in special populations [9] — children, older adults, pregnancy, renal and hepatic impairment, transplant and haematology patients. The argued advantages are fewer neurovisual side effects than voriconazole, no cyclodextrin vehicle for the intravenous formulation, and a favourable QT profile. The authors are clear that routine therapeutic drug monitoring is not supported by any validated universal exposure target, but selective monitoring makes sense with altered pharmacokinetics, extracorporeal support, suspected failure or major interactions. The third exposure paper is in the Journal of Infectious Diseases, where Wu and colleagues addressed a long-standing worry about tenofovir-based pre-exposure prophylaxis in pregnancy [10]. Using directly observed daily dosing over eight weeks in eighteen pregnant and eighteen non-pregnant Kenyan women — with essentially every dose witnessed — they confirmed that dried blood spot tenofovir diphosphate concentrations were about forty percent lower in pregnancy. But concentrations inside peripheral blood mononuclear cells, the cells that actually matter for HIV protection, were not meaningfully different between pregnant and non-pregnant women. The practical implication is important: lower dried blood spot levels in pregnancy reflect altered red cell kinetics and higher renal clearance, not inadequate target-site drug. Do not read a pregnant patient's dried blood spot result against non-pregnant adherence thresholds and conclude she is non-adherent or under-dosed.

Finally, prevention and end-of-life care. In The Lancet Infectious Diseases, Essink and colleagues report a phase 3 trial of an MF59-adjuvanted, cell-derived, higher-dose quadrivalent influenza vaccine in nearly seven thousand seven hundred adults aged fifty and over [3]. Lot-to-lot consistency was met, and the new vaccine was both non-inferior and superior to standard adjuvanted egg-derived vaccine for all four strains, with seroconversion advantages ranging from about ten to twenty-four percentage points. Against recombinant vaccine, though, the result was mixed: non-inferiority was met for three strains but not for A H3N2, where the new vaccine performed worse — and H3N2 is the strain that drives most severe seasons in older adults. Reactogenicity was higher but mostly mild to moderate. Immunogenicity is not efficacy, so treat this as a promising but incomplete case. Two other papers round out the week. In Clinical Infectious Diseases, Crowley and colleagues examined antibiotic prescribing in more than six thousand outpatient hospice patients [4]; about one in five received an antimicrobial, and in time-dependent models antibiotic use was associated with roughly a fifty percent higher hazard of death, strongest in patients with cancer as the hospice-qualifying condition. There was, however, an apparent survival benefit in the subgroup whose qualifying condition was infectious. This is observational and confounding by indication is the obvious explanation — antibiotics are started when patients deteriorate — but it is useful evidence for the goals-of-care conversation, that antibiotics near the end of life rarely prolong it. And in Antimicrobial Agents and Chemotherapy, Rabinovich and colleagues report forty years of benznidazole treatment for Chagas disease in Argentina, covering 464 patients, most of them children [5]. All patients cleared parasitaemia by the end of treatment, and at one year close to forty percent of patients showed a meaningful fall in antibody titres while roughly thirty percent of patients had seroreverted, with younger patients converting fastest — a strong argument for treating early.

If you only have time for one paper this week, make it the TriNetX comparison of cefazolin versus antistaphylococcal penicillins in MSSA bacteraemia [1]. It addresses a decision most of us make every month, and it adds substantial real-world weight to the case for cefazolin as the default.

Here are the key takeaways from this week in Infectious Disease. First, in MSSA bacteraemia, large real-world data again favour cefazolin over antistaphylococcal penicillins for both mortality and C. difficile risk. Second, for carbapenem-resistant Enterobacterales, aztreonam-avibactam retained near-universal activity across Asia Pacific and Latin America where the older beta-lactamase inhibitor combinations did not, and ceftazidime-avibactam exposure repeatedly selects the KPC-33 variant with no reliable fitness penalty — so re-culture and retest during prolonged therapy. Third, in pregnancy, dried blood spot tenofovir diphosphate is about forty percent lower but intracellular concentrations in mononuclear cells are preserved; do not misinterpret this as non-adherence. Fourth, the new adjuvanted cell-derived higher-dose influenza vaccine beat adjuvanted egg-derived vaccine on immunogenicity but fell short of recombinant vaccine for A H3N2. And fifth, in hospice, antibiotics were associated with higher, not lower, mortality outside of infectious qualifying conditions — worth remembering when families ask.

That's your roundup for This Week in Infectious Disease. The full transcript and references are available on the episode page in your AudioScholar library. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.

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