Impact of contusion injury on intramuscular emm1 group a streptococcus infection and lymphatic spread.

Invasive group A Streptococcus (iGAS) is frequently associated with emm1 isolates, with an attendant mortality of around 20%. Cases occasionally arise in previously healthy individuals with a history of upper respiratory tract infection, soft tissue contusion, and no obvious portal of entry. Using a new murine model of contusion, we determined the impact of contusion on iGAS bacterial burden and phenotype. Calibrated mild blunt contusion did not provide a focus for initiation or seeding of GAS that was detectable following systemic GAS bacteremia, but instead enhanced GAS migration to the local draining lymph node following GAS inoculation at the same time and site of contusion. Increased migration to lymph node was associated with emergence of mucoid bacteria, although was not specific to mucoid bacteria. In one study, mucoid colonies demonstrated a significant increase in capsular hyaluronan that was not linked to a covRS or rocA mutation, but to a deletion in the promoter of the capsule synthesis locus, hasABC, resulting in a strain with increased fitness for lymph node migration. In summary, in the mild contusion model used, we could not detect seeding of muscle by GAS. Contusion promoted bacterial transit to the local lymph node. The consequences of contusion-associated bacterial lymphatic migration may vary depending on the pathogen and virulence traits selected.

Severe septic-shock like reaction to co-trimoxazole in an HIV-positive man.

Adverse drug reactions occur at a greater frequency in HIV-infected individuals. A 38-year-old Eritrean man was treated with outpatient co-trimoxazole for confirmed Pneumocystis jirovecii pneumonia, but was switched to clindamycin and primaquine due to nausea and vomiting. Following development of methaemaglobinaemia, he was recommenced on prophylactic co-trimoxazole. He was later found moribund with features resembling septic shock and required invasive respiratory support. The diagnosis of a rare, but severe reaction to co-trimoxazole did not become apparent until he was rechallenged with prophylactic co-trimoxazole after recovery from his initial severe reaction. In an era of polypharmacy and an increasing availability of novel drugs, this case is a timely reminder to clinicians of the ongoing need for pharmacovigilance, especially in HIV-infected individuals who may have unusual presentations of an adverse drug reaction.

Reduced glomerular filtration rate but sustained virologic response in HIV/hepatitis B co-infected individuals on long-term tenofovir.

Reports have described a decrease in glomerular filtration rate (eGFR) associated with tenofovir disoproxil fumarate (TDF) use in HIV positive individuals. However, no study has examined renal function over a prolonged period in HIV/hepatitis B virus (HBV) co-infected patients. We assessed the long-term durability and toxicity of TDF in a cohort of 39 e antigen (eAg) positive co-infected patients commenced on TDF 245 mg daily either in addition to or as part of standard antiretroviral therapy. Immunological and virological parameters were followed to 260 weeks, with the median follow-up period being 251 weeks (range 69-290 weeks). eGFR was calculated using the Modification in Diet in Renal Disease equation. On treatment at 260 weeks, 88% (14/16) had HIV viral load <50 copies/mL, median CD4 count rose from 318 to 532 cells/mm(3), median alanine aminotransferase (ALT) fell from 61 IU/L to 42 IU/L, with 35% (7/20) having a normal ALT, median HBV DNA fell from 69 x 10(6) copies/mL to 500 copies/mL, with 75% (12/16) having an undetectable HBV DNA level and 55% (6/11) becoming eAg negative. Of those with detectable HBV DNA, none had TDF resistance mutations. The eGFR declined by 22.19 mL/min/1.73 mm(2) from baseline (P = 0.023) over this period, which was unaffected by protease inhibitor use, baseline CD4 count, ALT or HBV DNA level. Three patients discontinued TDF therapy due to renal dysfunction. In conclusion, TDF has sustained efficacy but is associated with a significant decline in eGFR. Further larger studies are required to clarify this observation.