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  1. von Delft A, Dramowski A, Sifumba Z, Mosidi T, Xun Ting T, von Delft D, et al.
    Clin Infect Dis, 2016 05 15;62 Suppl 3:S275-80.
    PMID: 27118858 DOI: 10.1093/cid/ciw037
    "Occupational MDR-TB"  …  "XDR-TB"  …  "Treatment-induced hearing loss": 3 life-changing messages imparted over the phone. Three personal accounts are shared highlighting the false belief held by many healthcare workers (HCWs) and students in low-resource settings-that they are immune to tuberculosis despite high levels of occupational tuberculosis exposure. This misconception reflects a lack of awareness of tuberculosis transmission and disease risk, compounded by the absence of accurate occupational tuberculosis estimates. As the global problem of drug-resistant (DR) tuberculosis evolves, HCWs are increasingly infected and suffer considerable morbidity and mortality from occupational DR tuberculosis disease. Similarly, healthcare students are emerging as a vulnerable and unprotected group. There is an urgent need for improved detection, vaccines, preventive therapy, treatment, and support for affected HCWs and those they care for, as well as destigmatization of all forms of tuberculosis. Finally, efforts to protect HCWs and prevent DR tuberculosis transmission by universal implementation of tuberculosis infection control measures should be prioritized.
  2. del Amo J, Moreno S, Bucher HC, Furrer H, Logan R, Sterne J, et al.
    Clin Infect Dis, 2012 May;54(9):1364-72.
    PMID: 22460971 DOI: 10.1093/cid/cis203
    BACKGROUND: The lower tuberculosis incidence reported in human immunodeficiency virus (HIV)-positive individuals receiving combined antiretroviral therapy (cART) is difficult to interpret causally. Furthermore, the role of unmasking immune reconstitution inflammatory syndrome (IRIS) is unclear. We aim to estimate the effect of cART on tuberculosis incidence in HIV-positive individuals in high-income countries.

    METHODS: The HIV-CAUSAL Collaboration consisted of 12 cohorts from the United States and Europe of HIV-positive, ART-naive, AIDS-free individuals aged ≥18 years with baseline CD4 cell count and HIV RNA levels followed up from 1996 through 2007. We estimated hazard ratios (HRs) for cART versus no cART, adjusted for time-varying CD4 cell count and HIV RNA level via inverse probability weighting.

    RESULTS: Of 65 121 individuals, 712 developed tuberculosis over 28 months of median follow-up (incidence, 3.0 cases per 1000 person-years). The HR for tuberculosis for cART versus no cART was 0.56 (95% confidence interval [CI], 0.44-0.72) overall, 1.04 (95% CI, 0.64-1.68) for individuals aged >50 years, and 1.46 (95% CI, 0.70-3.04) for people with a CD4 cell count of <50 cells/μL. Compared with people who had not started cART, HRs differed by time since cART initiation: 1.36 (95% CI, 0.98-1.89) for initiation <3 months ago and 0.44 (95% CI, 0.34-0.58) for initiation ≥3 months ago. Compared with people who had not initiated cART, HRs <3 months after cART initiation were 0.67 (95% CI, 0.38-1.18), 1.51 (95% CI, 0.98-2.31), and 3.20 (95% CI, 1.34-7.60) for people <35, 35-50, and >50 years old, respectively, and 2.30 (95% CI, 1.03-5.14) for people with a CD4 cell count of <50 cells/μL.

    CONCLUSIONS: Tuberculosis incidence decreased after cART initiation but not among people >50 years old or with CD4 cell counts of <50 cells/μL. Despite an overall decrease in tuberculosis incidence, the increased rate during 3 months of ART suggests unmasking IRIS.

  3. Zelenev A, Li J, Shea P, Hecht R, Altice FL
    Clin Infect Dis, 2021 03 01;72(5):755-763.
    PMID: 32060534 DOI: 10.1093/cid/ciaa142
    BACKGROUND: Hepatitis C virus (HCV) treatment as prevention (TasP) strategies can contribute to HCV microelimination, yet complimentary interventions such as opioid agonist therapies (OAT) with methadone or buprenorphine and syringe services programs (SSPs) may improve the prevention impact. This modeling study estimates the impact of scaling up the combination of OAT and SSPs with HCV TasP in a network of people who inject drugs (PWID) in the United States.

    METHODS: Using empirical data from Hartford, Connecticut, we deployed a stochastic block model to simulate an injection network of 1574 PWID. We used a susceptible-infected model for HCV and human immunodeficiency virus to evaluate the effectiveness of several HCV TasP strategies, including in combination with OAT and SSP scale-up, over 20 years.

    RESULTS: At the highest HCV prevalence (75%), when OAT coverage is increased from 10% to 40%, combined with HCV treatment of 10% per year and SSP scale up to 40%, the time to achieve microelimination is reduced from 18.4 to 11.6 years. At the current HCV prevalence (60%), HCV TasP strategies as low as 10% coverage per year may achieve HCV microelimination within 10 years, with minimal impact from additional OAT scale-up. Strategies based on mass initial HCV treatment (50 per 100 PWID the first year followed by 5 per 100 PWID thereafter) were most effective in settings with HCV prevalence of 60% or lower.

    CONCLUSIONS: Scale-up of HCV TasP is the most effective strategy for microelimination of HCV. OAT scale-up, however, scale-up may be synergistic toward achieving microelimination goals when HCV prevalence exceeds 60% and when HCV treatment coverage is 10 per 100 PWID per year or lower.

  4. Vlasova AN, Diaz A, Damtie D, Xiu L, Toh TH, Lee JS, et al.
    Clin Infect Dis, 2022 02 11;74(3):446-454.
    PMID: 34013321 DOI: 10.1093/cid/ciab456
    BACKGROUND: During the validation of a highly sensitive panspecies coronavirus (CoV) seminested reverse-transcription polymerase chain reaction (RT-PCR) assay, we found canine CoV (CCoV) RNA in nasopharyngeal swab samples from 8 of 301 patients (2.5%) hospitalized with pneumonia during 2017-2018 in Sarawak, Malaysia. Most patients were children living in rural areas with frequent exposure to domesticated animals and wildlife.

    METHODS: Specimens were further studied with universal and species-specific CoV and CCoV 1-step RT-PCR assays, and viral isolation was performed in A72 canine cells. Complete genome sequencing was conducted using the Sanger method.

    RESULTS: Two of 8 specimens contained sufficient amounts of CCoVs as confirmed by less-sensitive single-step RT-PCR assays, and 1 specimen demonstrated cytopathic effects in A72 cells. Complete genome sequencing of the virus causing cytopathic effects identified it as a novel canine-feline recombinant alphacoronavirus (genotype II) that we named CCoV-human pneumonia (HuPn)-2018. Most of the CCoV-HuPn-2018 genome is more closely related to a CCoV TN-449, while its S gene shared significantly higher sequence identity with CCoV-UCD-1 (S1 domain) and a feline CoV WSU 79-1683 (S2 domain). CCoV-HuPn-2018 is unique for a 36-nucleotide (12-amino acid) deletion in the N protein and the presence of full-length and truncated 7b nonstructural protein, which may have clinical relevance.

    CONCLUSIONS: This is the first report of a novel canine-feline recombinant alphacoronavirus isolated from a human patient with pneumonia. If confirmed as a pathogen, it may represent the eighth unique coronavirus known to cause disease in humans. Our findings underscore the public health threat of animal CoVs and a need to conduct better surveillance for them.

  5. Toller Erausquin J, Tan RKJ, Uhlich M, Francis JM, Kumar N, Campbell L, et al.
    Clin Infect Dis, 2022 Aug 24;75(1):e991-e999.
    PMID: 35136960 DOI: 10.1093/cid/ciac102
    BACKGROUND: There is limited evidence to date about changes to sexual and reproductive health (SRH) during the initial wave of coronavirus disease 2019 (COVID-19). To address this gap, our team organized a multicountry, cross-sectional online survey as part of a global consortium.

    METHODS: Consortium research teams conducted online surveys in 30 countries. Sampling methods included convenience, online panels, and population-representative. Primary outcomes included sexual behaviors, partner violence, and SRH service use, and we compared 3 months prior to and during policy measures to mitigate COVID-19. We conducted meta-analyses for primary outcomes and graded the certainty of the evidence.

    RESULTS: Among 4546 respondents with casual partners, condom use stayed the same for 3374 (74.4%), and 640 (14.1%) reported a decline. Fewer respondents reported physical or sexual partner violence during COVID-19 measures (1063 of 15 144, 7.0%) compared to before COVID-19 measures (1469 of 15 887, 9.3%). COVID-19 measures impeded access to condoms (933 of 10 790, 8.7%), contraceptives (610 of 8175, 7.5%), and human immunodeficiency virus/sexually transmitted infection (HIV/STI) testing (750 of 1965, 30.7%). Pooled estimates from meta-analysis indicate that during COVID-19 measures, 32.3% (95% confidence interval [CI], 23.9%-42.1%) of people needing HIV/STI testing had hindered access, 4.4% (95% CI, 3.4%-5.4%) experienced partner violence, and 5.8% (95% CI, 5.4%-8.2%) decreased casual partner condom use (moderate certainty of evidence for each outcome). Meta-analysis findings were robust in sensitivity analyses that examined country income level, sample size, and sampling strategy.

    CONCLUSIONS: Open science methods are feasible to organize research studies as part of emergency responses. The initial COVID-19 wave impacted SRH behaviors and access to services across diverse global settings.

  6. Teerawattanapong N, Kengkla K, Dilokthornsakul P, Saokaew S, Apisarnthanarak A, Chaiyakunapruk N
    Clin Infect Dis, 2017 May 15;64(suppl_2):S51-S60.
    PMID: 28475791 DOI: 10.1093/cid/cix112
    Background: This study evaluated the relative efficacy of strategies for the prevention of multidrug-resistant gram-negative bacteria (MDR-GNB) in adult intensive care units (ICUs).

    Methods: A systematic review and network meta-analysis was performed; searches of the Cochrane Library, PubMed, Embase, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) included all randomized controlled trials and observational studies conducted in adult patients hospitalized in ICUs and evaluating standard care (STD), antimicrobial stewardship program (ASP), environmental cleaning (ENV), decolonization methods (DCL), or source control (SCT), simultaneously. The primary outcomes were MDR-GNB acquisition, colonization, and infection; secondary outcome was ICU mortality.

    Results: Of 3805 publications retrieved, 42 met inclusion criteria (5 randomized controlled trials and 37 observational studies), involving 62068 patients (median age, 58.8 years; median APACHE [Acute Physiology and Chronic Health Evaluation] II score, 18.9). The majority of studies reported extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and MDR Acinetobacter baumannii. Compared with STD, a 4-component strategy composed of STD, ASP, ENV, and SCT was the most effective intervention (rate ratio [RR], 0.05 [95% confidence interval {CI}, .01-.38]). When ENV was added to STD+ASP or SCT was added to STD+ENV, there was a significant reduction in the acquisition of MDR A. baumannii (RR, 0.28 [95% CI, .18-.43] and 0.48 [95% CI, .35-.66], respectively). Strategies with ASP as a core component showed a statistically significant reduction the acquisition of ESBL-producing Enterobacteriaceae (RR, 0.28 [95% CI, .11-.69] for STD+ASP+ENV and 0.23 [95% CI, .07-.80] for STD+ASP+DCL).

    Conclusions: A 4-component strategy was the most effective intervention to prevent MDR-GNB acquisition. As some strategies were differential for certain bacteria, our study highlighted the need for further evaluation of the most effective prevention strategies.

  7. Sungkanuparph S, Oyomopito R, Sirivichayakul S, Sirisanthana T, Li PC, Kantipong P, et al.
    Clin Infect Dis, 2011 Apr 15;52(8):1053-7.
    PMID: 21460324 DOI: 10.1093/cid/cir107
    Of 682 antiretroviral-naïve patients initiating antiretroviral therapy in a prospective, multicenter human immunodeficiency virus type 1 (HIV-1) drug resistance monitoring study involving 8 sites in Hong Kong, Malaysia, and Thailand, the prevalence of patients with ≥1 drug resistance mutation was 13.8%. Primary HIV drug resistance is emerging after rapid scaling-up of antiretroviral therapy use in Asia.
  8. Song JH, Lee NY, Ichiyama S, Yoshida R, Hirakata Y, Fu W, et al.
    Clin Infect Dis, 1999 Jun;28(6):1206-11.
    PMID: 10451154
    Antimicrobial susceptibility of 996 isolates of Streptococcus pneumoniae from clinical specimens was investigated in 11 Asian countries from September 1996 to June 1997. Korea had the greatest frequency of nonsusceptible strains to penicillin with 79.7%, followed by Japan (65.3%), Vietnam (60.8%), Thailand (57.9%), Sri Lanka (41.2%), Taiwan (38.7%), Singapore (23.1%), Indonesia (21.0%), China (9.8%), Malaysia (9.0%), and India (3.8%). Serotypes 23F and 19F were the most common. Pulsed-field gel electrophoresis (PFGE) of 154 isolates from Asian countries showed several major PFGE patterns. The serotype 23F Spanish clone shared the same PFGE pattern with strains from Korea, Japan, Singapore, Taiwan, Thailand, and Malaysia. Fingerprinting analysis of pbp1a, pbp2x, and pbp2b genes of 12 strains from six countries also showed identical fingerprints of penicillin-binding protein genes in most strains. These data suggest the possible introduction and spread of international epidemic clones into Asian countries and the increasing problems of pneumococcal drug resistance in Asian countries for the first time.
  9. Roberts JA, Joynt GM, Lee A, Choi G, Bellomo R, Kanji S, et al.
    Clin Infect Dis, 2021 04 26;72(8):1369-1378.
    PMID: 32150603 DOI: 10.1093/cid/ciaa224
    BACKGROUND: The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets.

    METHODS: We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations.

    RESULTS: We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4-8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35-65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P < .05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9-18.8), piperacillin was 78.6 mg/L (49.5-127.3), tazobactam was 9.5 mg/L (6.3-14.2), and vancomycin was 14.3 mg/L (11.6-21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively.

    CONCLUSIONS: In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.

  10. Rao M, Rashid FA, Sabri FSAH, Jamil NN, Zain R, Hashim R, et al.
    Clin Infect Dis, 2021 05 04;72(9):e352-e356.
    PMID: 32761244 DOI: 10.1093/cid/ciaa1156
    BACKGROUND: The ideal severe acute respiratory syndrome coronavirus 2 (SARs-CoV-2) testing method would be accurate and also be patient-performed to reduce exposure to healthcare workers. The aim of this study was to compare patient-performed testing based on a morning saliva sample with the current standard testing method, healthcare worker-collected sampling via a nasopharyngeal swab (NPS).

    METHODS: This was a prospective single center study which recruited 217 asymptomatic adult male participants in a coronavirus disease 2019 (COVID-19) quarantine center who had tested positive for SARS-CoV-2 8-10 days prior to isolation. Paired NPS and saliva specimens were collected and processed within 5 hours of sample collection. Real time reverse transcription polymerase chain reaction (RT-PCR) targeting Envelope (E) and RNA-dependent RNA polymerase (RdRp) genes was performed and the results were compared.

    RESULTS: Overall, 160 of the 217 (74%) participants tested positive for COVID-19 based on saliva, NPS, or both testing methods. The detection rate for SARS-CoV-2 was higher in saliva compared to NPS testing (93.1%, 149/160 vs 52.5%, 84/160, P < .001). The concordance between the 2 tests was 45.6% (virus was detected in both saliva and NPS in 73/160), whereas 47.5% were discordant (87/160 tested positive for 1 whereas negative for the other). The cycle threshold (Ct) values for E and RdRp genes were significantly lower in saliva specimens compared to NP swab specimens.

    CONCLUSIONS: Our findings demonstrate that saliva is a better alternative specimen for detection of SARS-CoV-2. Taking into consideration, the simplicity of specimen collection, shortage of PPE and the transmissibility of the virus, saliva could enable self-collection for an accurate SARS-CoV-2 surveillance testing.

  11. Rajahram GS, Cooper DJ, William T, Grigg MJ, Anstey NM, Barber BE
    Clin Infect Dis, 2019 10 30;69(10):1703-1711.
    PMID: 30624597 DOI: 10.1093/cid/ciz011
    BACKGROUND: Plasmodium knowlesi causes severe and fatal malaria, and incidence in Southeast Asia is increasing. Factors associated with death are not clearly defined.

    METHODS: All malaria deaths in Sabah, Malaysia, from 2015 to 2017 were identified from mandatory reporting to the Sabah Department of Health. Case notes were reviewed, and a systematic review of these and all previously reported fatal P. knowlesi cases was conducted. Case fatality rates (CFRs) during 2010-2017 were calculated using incidence data from the Sabah Department of Health.

    RESULTS: Six malaria deaths occurred in Sabah during 2015-2017, all from P. knowlesi. Median age was 40 (range, 23-58) years; 4 cases (67%) were male. Three (50%) had significant cardiovascular comorbidities and 1 was pregnant. Delays in administering appropriate therapy contributed to 3 (50%) deaths. An additional 26 fatal cases were included in the systematic review. Among all 32 cases, 18 (56%) were male; median age was 56 (range, 23-84) years. Cardiovascular-metabolic disease, microscopic misdiagnosis, and delay in commencing intravenous treatment were identified in 11 of 32 (34%), 26 of 29 (90%), and 11 of 31 (36%) cases, respectively. The overall CFR during 2010-2017 was 2.5/1000: 6.0/1000 for women and 1.7/1000 for men (P = .01). Independent risk factors for death included female sex (odds ratio, 2.6; P = .04), and age ≥45 years (odds ratio, 4.7; P < .01).

    CONCLUSIONS: Earlier presentation, more rapid diagnosis, and administration of intravenous artesunate may avoid fatal outcomes, particularly in females, older adults, and patients with cardiovascular comorbidities.

  12. Ooi MH, Lewthwaite P, Lai BF, Mohan A, Clear D, Lim L, et al.
    Clin Infect Dis, 2008 Aug 15;47(4):458-68.
    PMID: 18616397 DOI: 10.1086/590008
    BACKGROUND: Japanese encephalitis is a major public health problem in Asia. However, there is little data on the long-term outcome of Japanese encephalitis survivors.

    METHODS: We prospectively evaluated children with serologically confirmed Japanese encephalitis over an 8.3-year period. The patients were assessed and their outcomes were graded with a functional outcome score at hospital discharge and at follow-up appointments. We examined how patient outcome at hospital discharge compared with that at long-term follow-up visits, when changes in outcome occurred, and the prognostic indicators of the eventual outcome.

    RESULTS: One hundred and eighteen patients were recruited into the study, and 10 (8%) died during the acute phase of illness. At hospital discharge, 44 (41%) of the 108 patients who survived had apparent full recovery; 3 (3%) had mild, 28 (26%) had moderate, and 33 (31%) had severe neurological sequelae. Eighty six of the 108 patients were followed up for a median duration of 52.9 months (range, 0.9-114.9 months). During follow-up, 31 patients experienced improvement, but 15 patients experienced deterioration in their outcome grade. In most cases, assessment during the first 3-6 months after hospital discharge was predictive of the long-term outcome. More than one-half of the patients continued to experience neuropsychological sequelae and behavioral disorders. A combination of poor perfusion, Glasgow coma score < or =8, and > or =2 witnessed seizures predicted a poor long-term outcome with 65% sensitivity and 92% specificity.

    CONCLUSIONS: Neurological assessment of Japanese encephalitis survivors at hospital discharge does not predict long-term outcome. Seizures and shock are treatable risk factors for a poor outcome at hospital discharge and at long-term follow-up visits.

  13. Ooi MH, Wong SC, Podin Y, Akin W, del Sel S, Mohan A, et al.
    Clin Infect Dis, 2007 Mar 01;44(5):646-56.
    PMID: 17278054
    BACKGROUND: Human enterovirus (HEV)-71 causes large outbreaks of hand-foot-and-mouth disease with central nervous system (CNS) complications, but the role of HEV-71 genogroups or dual infection with other viruses in causing severe disease is unclear.

    METHODS: We prospectively studied children with suspected HEV-71 (i.e., hand-foot-and-mouth disease, CNS disease, or both) over 3.5 years, using detailed virological investigation and genogroup analysis of all isolates.

    RESULTS: Seven hundred seventy-three children were recruited, 277 of whom were infected with HEV-71, including 28 who were coinfected with other viruses. Risk factors for CNS disease in HEV-71 included young age, fever, vomiting, mouth ulcers, breathlessness, cold limbs, and poor urine output. Genogroup analysis for the HEV-71-infected patients revealed that 168 were infected with genogroup B4, 68 with C1, and 41 with a newly emerged genogroup, B5. Children with HEV-71 genogroup B4 were less likely to have CNS complications than those with other genogroups (26 [15%] of 168 vs. 30 [28%] of 109; odds ratio [OR], 0.48; 95% confidence interval [CI], 0.26-0.91; P=.0223) and less likely to be part of a family cluster (12 [7%] of 168 vs. 29 [27%] of 109; OR, 0.21; 95% CI, 0.10-0.46; P

  14. Ooi MH, Wong SC, Clear D, Perera D, Krishnan S, Preston T, et al.
    Clin Infect Dis, 2003 Mar 1;36(5):550-9.
    PMID: 12594634
    We report the virological and clinical features of 8 children who presented with adenovirus-associated acute flaccid paralysis (AFP) during an epidemic of enterovirus type 71 (EV71)-associated hand-foot-and-mouth disease (HFMD) in Sarawak, Malaysia, in 1997. Neutralization tests and phylogenetic analysis revealed adenovirus type 21 (Ad21), although DNA restriction digests suggested that this virus was different from the prototype Ad21. Four children had upper-limb monoparesis, 2 had lower-limb monoparesis (one of whom had changes in the anterior spinal cord noted on magnetic resonance imaging), and 2 had flaccid paraparesis. At follow-up, 4 children were noted to have made full recoveries and 3 had residual flaccid weakness and wasting. Neurophysiological investigation revealed a mixture of axonal and demyelinating features in motor and sensory nerves, with denervation. These findings suggest that Ad21 might cause AFP by anterior horn cell damage or neuropathy of the brachial or lumbosacral plexus. The occurrence of these unusual adenovirus infections during an outbreak of EV71-associated HFMD suggests that an interaction between the 2 viruses may have occurred.
  15. Ooi MH, Ngu SJ, Chor YK, Li J, Landersdorfer CB, Nation RL
    Clin Infect Dis, 2019 11 13;69(11):1962-1968.
    PMID: 30722017 DOI: 10.1093/cid/ciz067
    BACKGROUND: Intravenous colistin is widely used to treat infections in pediatric patients. Unfortunately, there is a paucity of pharmacological information to guide the selection of dosage regimens. The daily dose recommended by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) is the same body weight-based dose traditionally used in adults. The aim was to increase our understanding of the patient factors that influence the plasma concentration of colistin, and assess the likely appropriateness of the FDA and EMA dosage recommendations.

    METHODS: There were 5 patients, with a median age of 1.75 (range 0.1-6.25) years, a median weight of 10.7 (2.9-21.5) kg, and a median creatinine clearance of 179 (44-384) mL/min/1.73m2, who received intravenous infusions of colistimethate each 8 hours. The median daily dose was 0.21 (0.20-0.21) million international units/kg, equivalent to 6.8 (6.5-6.9) mg of colistin base activity per kg/day. Plasma concentrations of colistimethate and formed colistin were subjected to population pharmacokinetic modeling to explore the patient factors influencing the concentration of colistin.

    RESULTS: The median, average, steady-state plasma concentration of colistin (Css,avg) was 0.88 mg/L; individual values ranged widely (0.41-3.50 mg/L), even though all patients received the same body weight-based daily dose. Although the daily doses were ~33% above the upper limit of the FDA- and EMA-recommended dose range, only 2 patients achieved Css,avg ≥2mg/L; the remaining 3 patients had Css,avg <1mg/L. The pharmacokinetic covariate analysis revealed that clearances of colistimethate and colistin were related to creatinine clearance.

    CONCLUSIONS: The FDA and EMA dosage recommendations may be suboptimal for many pediatric patients. Renal functioning is an important determinant of dosing in these patients.

  16. Noushad M, Al-Awar MS, Al-Saqqaf IS, Nassani MZ, Alrubaiee GG, Rastam S
    Clin Infect Dis, 2022 Nov 14;75(10):1827-1833.
    PMID: 35134160 DOI: 10.1093/cid/ciac088
    BACKGROUND: Vaccine hesitancy and vaccine inequity are 2 major hurdles toward achieving population immunity to coronavirus disease 2019 (COVID-19). Although several studies have been published on vaccine hesitancy among numerous populations, there is inadequate information on any potential correlation between vaccine acceptance and lack of access to vaccines. Our cross-sectional study in a low-income country aimed to fill this gap.

    METHODS: We conducted a nation-wide cross-sectional survey among the general population in Yemen, a low-income conflict country. Participants from all provinces in Yemen were included in the study. We evaluated factors that influence agreement to accept a COVID-19 vaccine and any potential correlation between vaccine hesitancy and lack of access to vaccines.

    RESULTS: Overall, 50.1% of the 5329 respondents agreed to accept a COVID-19 vaccine. Only 39.9% of participants agreed that they had access to a COVID-19 vaccine, with females indicating lower access than males. Potential determinants of vaccine acceptance included being male, updating self on the development of vaccines against COVID-19, opinion about severity of COVID-19, anxiety about contracting COVID-19, concerns about the safety of COVID-19 vaccines, and lack of access to vaccines.

    CONCLUSIONS: Our results indicate that the immediate threat in Yemen toward achieving population immunity is the severe shortage and lack of access to vaccines, rather than vaccine hesitancy.

  17. Ng KT, Ng KY, Chen JH, Ng OT, Kamarulzaman A, Tee KK
    Clin Infect Dis, 2014 Sep 15;59(6):910-1.
    PMID: 24944233 DOI: 10.1093/cid/ciu480
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