This report describes a case of ciprofloxacin treatment failure in a patient with enteric fever caused by Salmonella enterica serotype Paratyphi A. The organism was isolated from a blood culture from a patient who was treated with oral ciprofloxacin (500 mg every 12 h) for 13 days. The organism showed reduced susceptibility to ciprofloxacin (MIC 0.75 mg ml "1 ) and was resistant to nalidixic acid. The patient was then placed on intravenous ceftriaxone (1 g every 12 h) and responded within 3 days. The patient was discharged after 9 days on ceftriaxone with no relapse on follow-up. This case adds to the increasing incidence of treatment failures with ciprofloxacin in typhoid fever caused by typhoid salmonellae with reduced susceptibility to ciprofloxacin. It also highlights the inadequacy of current laboratory methods for fluoroquinolone susceptibility testing in adequately predicting in vivo activity of ciprofloxacin against typhoid salmonellae and supports calls for new guidelines for fluoroquinolone susceptibility testing of these organisms.

It is very important to keep searching for new mutations and continuously monitor drug resistance in different parts of the world in order to efficiently manage cases with enteric fever.

Mutations associated with resistance to antiretroviral therapy are a major cause of failure to treatment, and surveillance for the emergence of HIV resistance became a component of all antiretroviral treatment programs. As transmission of resistant viruses to newly infected persons is possible, we aimed to determine the prevalence of primary mutations associated with antiretroviral resistance among treatment-naïve patients, with respect to HIV subtype. Viral RNA was extracted from plasma samples of 43 treatment-naïve patients. Protease (PR) and reverse transcriptase (RT) regions were amplified and sequenced using the TRUGENE HIV-1 Genotyping Assay. A phylogenetic analysis was performed for HIV subtype assignment. Complete sequence information could be obtained for 35 patients. A total of ten different HIV-1 subtypes and recombinant forms were found in Kuwait with predominance of subtypes B, C, and CRF01_AE. A62V and A98G were non-polymorphic resistance-associated mutations (RAMs) detected in the RT region of two and three patients, respectively. Non-polymorphic mutations associated with resistance to protease inhibitors were not detected. Our results support continuous surveillance of RAMs in newly infected individuals to assess the effectiveness of first-line antiretroviral regimen available in Kuwait.

Objectives: Resistance-associated mutations (RAMs) in the integrase of different HIV-1 subtypes were investigated in a cohort of patients never exposed to integrase strand transfer inhibitors (INSTIs). Methods: The viral RNA was extracted from plasma samples of 53 INSTI-naïve patients, and the integrase genetic region was sequenced and analyzed for subtype assignment and drug resistance. Results: The median viral load at sampling was 5.28 × 10⁴ RNA copies/mL. Bayesian phylogenetic analysis showed 85% of the HIV-1 isolates were non-B subtypes, with a predominance of subtypes C (22.6%) and CRF01_AE (26.4%). A total of 52 and 110 mutations were found in the integrase region of HIV-1 B and non-B subtypes, respectively. Nonpolymorphic INSTI-RAMs were not detected in this study. However, the accessory mutation E157Q was found in 1 patient with CRF02_AG, and the polymorphic mutations L74M/I that may contribute to a reduced susceptibility to INSTIs in the presence of major mutations were observed in 6 (13.3%) patients with non-B subtypes and 1 (12.5%) patient with the B subtype. Polymorphic mutations at positions known to harbor primary and accessory RAMs were also detected in this study. Conclusion: Our results highlight the importance of monitoring the emergence of INSTI-RAMS before and after the initiation of INSTI-based therapy.

Objectives: To investigate the prevalence of nonpolymorphic resistance-associated mutations (RAM) in HIV-1 patients on first-line antiretroviral therapy in Kuwait. Subjects and Methods: Total RNA was isolated from plasma samples of 42 patients who received a first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. HIV-1 protease and reverse transcriptase genetic regions were then amplified by nested reverse transcription-polymerase chain reaction and directly sequenced. The HIV-1 subtype was identified using the Bayesian phylogenetic method, and RAM were identified using the Stanford University genotypic resistance interpretation algorithm. Results: The HIV-1 viral load at sampling ranged from < 20 to 8.25 × 10⁴ copies/ml. CRF01_AE, C, and B were the most predominant HIV-1 subtypes. Nonpolymorphic mutations associated with resistance to antiretroviral drugs were detected in 11 (26.2%) of the 42 patients; 5 (11.9%) patients had mutations associated with a high-level resistance to nucleoside reverse transcriptase inhibitors (NRTI), 4 (9.5%) patients had mutations associated with resistance to NNRTI, 1 (2.4%) patient had mutations associated with resistance to both NRTI and NNRTI, and 1 (2.4%) patient had mutations potentially associated with low-level resistance to both protease inhibitors and NNRTI. All patients with RAM had a detectable plasma HIV-1 RNA level. Conclusion: Our results indicate the development of RAM during an NNRTI-based regimen and highlight the importance of considering other regimens to avoid treatment failure.