Plasma and tissue concentrations of 2 g prophylactic cefazolin prior to lower extremity surgery.

Surgical site infections (SSIs) are among the most clinically relevant complications and the use of prophylactic cefazolin is common practice. However, the knowledge about the pharmacological aspects of prophylactic cefazolin in the lower extremities remains limited. In this prospective cohort, a sub-study of the WIFI-2 randomized controlled trial, adults between 18 and 75 years of age who were scheduled for implant removal below the level of the knee and randomized for cefazolin, was included. A maximum of two venous plasma, target-site plasma, and target-site tissue samples were taken during surgery. The primary outcomes were the cefazolin concentrations in venous plasma, target-site plasma, and target-site tissue. A total of 27 patients [median (interquartile range) age, 42 (29-59) years; 17 (63%) male] with 138 samples were included in the study. A minimum of 6 weeks follow-up was available for all patients. The mean (SD) venous plasma, target-site plasma, and target-site tissue concentrations were 36 (13) µg/mL, 29 (13) µg/mL, and 28 (13) µg/g, respectively, and the cefazolin concentrations between the different locations of surgery did not differ significantly in both target-site plasma and target-site tissue (P = 0.822 and P = 0.840). In conclusion, 2 g of prophylactic cefazolin demonstrates adequacy in maintaining coverage for a duration of at least 80 minutes of surgery below the level of the knee, significantly surpassing the MIC90 required to combat the most prevalent microorganisms. This study represents the first of its kind to assess cefazolin concentrations in the lower extremities by examining both plasma and tissue samples in this magnitude.

Fusariosis in patients with hematological malignancies: Two case reports.

Immunosuppressed patients with hematological malignancies are at risk for invasive fungal infections (IFI), including infections with Fusarium species (spp.), which are increasingly reported. Particularly at risk are patients with acute myeloid leukemia (AML) treated with high-dose cytarabine as remission-induction therapy. Whether cytarabine increases the risk of IFI in comparison to other chemotherapy remains not fully determined. Additionally, no clear correlation between the in vitro established minimal inhibitory concentrations (MICs) of antifungal agents and clinical outcome has been established for fusariosis. To increase awareness and knowledge of invasive fusariosis, we report two cases of Fusarium spp. infections in neutropenic patients following treatment with cytarabine for AML. Despite high MICs for azoles both patients were treated with an azole in combination with liposomal amphotericin B. The combination therapy was successful in one patient, however the other patient did not survive the disseminated Fusarium infection.

Population Pharmacokinetics and Probability of Target Attainment of Different Dosing Regimens of Ceftazidime in Critically Ill Patients with a Proven or Suspected Pseudomonas aeruginosa Infection.

Altered pharmacokinetics (PK) of hydrophilic antibiotics in critically ill patients is common, with possible consequences for efficacy and resistance. We aimed to describe ceftazidime population PK in critically ill patients with a proven or suspected Pseudomonas aeruginosa infection and to establish optimal dosing. Blood samples were collected for ceftazidime concentration measurement. A population PK model was constructed, and probability of target attainment (PTA) was assessed for targets 100% T > MIC and 100% T > 4 × MIC in the first 24 h. Ninety-six patients yielded 368 ceftazidime concentrations. In a one-compartment model, variability in ceftazidime clearance (CL) showed association with CVVH. For patients not receiving CVVH, variability in ceftazidime CL was 103.4% and showed positive associations with creatinine clearance and with the comorbidities hematologic malignancy, trauma or head injury, explaining 65.2% of variability. For patients treated for at least 24 h and assuming a worst-case MIC of 8 mg/L, PTA was 77% for 100% T > MIC and 14% for 100% T > 4 × MIC. Patients receiving loading doses before continuous infusion demonstrated higher PTA than patients who did not (100% T > MIC: 95% (n = 65) vs. 13% (n = 15); p < 0.001 and 100% T > 4 × MIC: 20% vs. 0%; p = 0.058). The considerable IIV in ceftazidime PK in ICU patients could largely be explained by renal function, CVVH use and several comorbidities. Critically ill patients are at risk for underexposure to ceftazidime when empirically aiming for the breakpoint MIC for P. aeruginosa. A loading dose is recommended.

The impact of trimethoprim-sulfamethoxazole as Pneumocystis jiroveci pneumonia prophylaxis on the occurrence of asymptomatic bacteriuria and urinary tract infections among renal allograft recipients: a retrospective before-after study.

BACKGROUND: The international guidelines recommend the administration of trimethoprim-sulfamethoxazole (TMP-SMX) as Pneumocystis jiroveci pneumonia (PJP) prophylaxis for six months after transplantation. The aim of this study is to evaluate the influence of TMP-SMX prophylaxis on the occurrence of asymptomatic bacteriuria (ASB) and urinary tract infections (UTIs) as cystitis and allograft pyelonephritis (AGPN) and its impact on the antimicrobial resistance pattern of causative microorganisms. METHODS: We have conducted a retrospective before-after study in adult renal allograft recipients with one year follow-up after transplantation. We compared the ("after") group that received TMP-SMX as PJP prophylaxis to the ("before") group that did not receive it. RESULTS: In total, 343 renal allograft recipients were analysed, of whom 212 (61.8 %) received TMP-SMX as PJP prophylaxis. In this study, 63 (18.4 %) did only develop ASB without UTI, 26 (7.6 %) developed cystitis and 43 (12.5 %) developed AGPN. The remaining 211 (61.5 %) renal allograft recipients did not develop any bacteriuria at all. Multivariable Cox proportional regression analysis indicated that TMP-SMX as PJP prophylaxis was not associated with reduced prevalence of ASB (Hazard ratio (HR) = 1.52, 95 % CI = 0.79-2.94, p = 0.213), nor with reduced incidence of cystitis (HR = 2.21, 95 % CI = 0.76-6.39, p = 0.144), nor AGPN (HR = 1.12, 95 % CI = 0.57-2.21, p = 0.751). Among the group receiving TMP-SMX as PJP prophylaxis there was a trend was observed in increase of both amoxicillin (86 % versus 70 %) and TMP-SMX (89 % versus 48 %) resistance which already appeared within the first 30 days after TMP-SMX exposure. CONCLUSIONS: Among renal allograft recipients, administration of TMP-SMX as PJP prophylaxis does not prevent ASB nor UTI, however it is associated with tendency towards increased amoxicillin and TMP-SMX resistance.

[Chagas disease in the Netherlands: an estimate of the number of patients]. / De ziekte van Chagas in Nederland: een schatting van het aantal patiënten.

A total of 8-10 million persons are infected worldwide with Trypanosoma cruzi, the causative parasite of Chagas disease, most of whom are inhabitants of Latin America. Due to the increased migration of peoples, Chagas disease has been on the uprise outside Latin America, including in Europe. The course of Chagas, also called American trypanosomiasis, runs in 2 phases: an acute phase lasting approximately 2 months, and a chronic phase in which symptoms may appear years after infection. Without treatment, the patient will remain infected for life. The acute phase is usually asymptomatic; in the chronic phase of American trypanosomiasis, severe gastro-intestinal and cardiac abnormalities may develop, finally with fatal course. In the Netherlands, the number of immigrants who would serologically test positive for American trypanosomiasis is estimated to be between 726 and 2929. Healthcare providers in the Netherlands may encounter patients who have Chagas disease more and more frequently. The screening of pregnant women and blood donors at risk for American trypanosomiasis should be considered.

Multiple-azole-resistant Aspergillus fumigatus osteomyelitis in a patient with chronic granulomatous disease successfully treated with long-term oral posaconazole and surgery.

We describe a patient with chronic granulomatous disease and proven Aspergillus fumigatus osteomyelitis of the midfoot, while receiving itraconazole-prophylaxis. The isolate proved resistant to itraconazole as well as voriconazole, and showed reduced susceptibility to posaconazole. Although molecular analysis demonstrated the presence of a 53 base pair tandem repeat in the promoter region for cyp51A, i.e., the gene coding for the target enzyme of the azole antifungals, there were no mutations in the cyp51A gene. Since transformation of the promoter region into wild-type strains did not result in an azole resistant phenotype, a yet unknown mutation was suspected. The patient was treated with extensive surgery and two weeks of caspofungin therapy, followed by one year of posaconazole therapy. He made a complete recovery and did not experience any side effects. Long-term posaconazole proved to be a safe and effective treatment for multi-azole resistant A. fumigatus osteomyelitis in this immunocompromised patient.