METHODS: A retrospective observational study was performed on consecutive adult cases of ESBL and AmpC bacteremia at the Alfred Hospital from 2014 through April 2018.
RESULTS: Among 110 patients with ESBL (88.2%) and AmpC (14.5%) bacteremia episodes, 96.4% had comorbidities such as hematological malignancy (30%). Approximately 45% were on immunosuppressive drugs, while 69% had recent antibiotic exposure. Over 84% of bacteremias were hospital acquired or healthcare associated. Urinary tract was the main source of infection (40%) with E. coli being the commonest organism (66.4%). The isolates were least resistant to gentamicin (21.8%), which was often appropriately used in empirical therapy. About 34% of patients presented with severe sepsis or shock. The 30-day mortality rate was 20% with no correlation with inappropriate empirical antibiotics (52%). There was no significant mortality difference between carbapenem use in empirical and definitive therapy. Respiratory source [OR 11.77, 95% CI 1.30-106.85; p = 0.03], severe sepsis or shock [OR 5.17, 95% CI 1.37-19.55; p = 0.02] and inappropriate definitive therapy [OR 27.93, 95%CI 3.69-211.35; p = 0.001] were independent predictors for mortality.
CONCLUSION: The choice and appropriateness of empirical therapy were not associated with mortality in ESBL and AmpC bacteremia. Prudent use of carbapenem is reasonable with gentamicin as alternative. Emphasis should be on prompt resuscitation in severe sepsis and early detection of ESBL and AmpC to facilitate appropriate switch to definitive therapy.
METHODS: A retrospective analytical cross-sectional study was conducted over 2 years. The cumulative antibiograms were constructed in accordance with current guidelines.
RESULTS: A total of 976 first isolate cultures were obtained from ICUs of the different referral hospitals. K. pneumoniae (8.8%, 8.1%) was a predominant pathogen in Windhoek Central hospital ICU in 2017 and 2018. In Oshakati intermediate hospital ICU, Enterobacter sp. (22.2%) and P. aeruginosa (37.5%) were the common pathogens in 2017 and 2018, respectively. A. baumannii isolates were >90% susceptibility to colistin, carbapenems, and tigecycline in 2017. In 2017, K. pneumoniae isolates were more susceptible to carbapenems (94% and 93.8% among isolates), amikacin (89.3%), and tigecycline (88.7%). In 2018, K. pneumoniae isolates were 100% susceptible amikacin, colistin, and carbapenems. S. maltophilia isolates were more than 80% susceptible to all the tested antibiotics. S. aureus isolates were 100% susceptible to linezolid, rifampicin, teicoplanin, and vancomycin in 2017 and in 2018. Its susceptibility to these antibiotics did not change.
CONCLUSION: The susceptibility patterns of the common isolated gram-negative pathogens were highly variable. Meropenem in combination with gentamicin is now the recommended antibiotic combination for empiric therapy for patients with LRTIs in Windhoek Central Hospital ICU.
Methods: Two complementary approaches, saturated transposon mutagenesis and spontaneous mutation induction with high concentrations of colistin and polymyxin B, were employed to select for mutations associated with resistance to polymyxins. Mutants were identified using transposon-directed insertion-site sequencing or Illumina WGS. A resistance phenotype was confirmed by MIC and further investigated using RT-PCR. Competitive growth assays were used to measure fitness cost.
Results: A transposon insertion at nucleotide 41 of the pmrB gene (EC958pmrB41-Tn5) enhanced its transcript level, resulting in a 64- and 32-fold increased MIC of colistin and polymyxin B, respectively. Three spontaneous mutations, also located within the pmrB gene, conferred resistance to both colistin and polymyxin B with a corresponding increase in transcription of the pmrCAB genes. All three mutations incurred a fitness cost in the absence of colistin and polymyxin B.
Conclusions: This study identified the pmrB gene as the main chromosomal target for induction of colistin and polymyxin B resistance in E. coli.
Methods: We searched PubMed, Embase and the Cochrane register of trials systematically for studies that examined treatment options for patients with MDR- and XDR-AB infections until April 2016. Network meta-analysis (NMA) was performed to estimate the risk ratio (RR) and 95% CI from both direct and indirect evidence. Primary outcomes were clinical cure and microbiological cure. Secondary outcomes were all-cause mortality and nephrotoxic and non-nephrotoxic adverse events.
Results: A total of 29 studies with 2529 patients (median age 60 years; 65% male; median APACHE II score 19.0) were included. Although there were no statistically significant differences between treatment options, triple therapy with colistin, sulbactam and tigecycline had the highest clinical cure rate. Colistin in combination with sulbactam was associated with a significantly higher microbiological cure rate compared with colistin in combination with tigecycline (RR 1.23; 95% CI 1.03-1.47) and colistin monotherapy (RR 1.21; 95% CI 1.06-1.38). No significant differences in all-cause mortality were noted between treatment options. Tigecycline-based therapy also appeared less effective for achieving a microbiological cure and is not appropriate for treating bloodstream MDR- and XDR-AB infections.
Conclusions: Combination therapy of colistin with sulbactam demonstrates superiority in terms of microbiological cure with a safety profile similar to that of colistin monotherapy. Thus, our findings support the use of this combination as a treatment for MDR- and XDR-AB infections.
METHODS: We did a systematic review and meta-analysis of primary antibiotic resistance to H pylori and the efficacy of first-line regimens in the Asia-Pacific region. We searched PubMed, Embase, and the Cochrane Library for articles published between Jan 1, 1990, and Sept 30, 2016; we also searched abstracts from international conferences. Both observational studies and randomised controlled trials were eligible for inclusion in the analysis of primary antibiotic resistance, but only randomised controlled trials were eligible for inclusion in the analysis of efficacy of first-line therapies. Meta-analysis was by the random-effects model to account for the substantial variations in resistance across the region. We did subgroup analyses by country and study period (ie, before 2000, 2001-05, 2006-10, and 2011-15) to establish country-specific prevalences of primary antibiotic resistance and first-line eradication rates. This study is registered with PROSPERO, number CRD42017057905.
FINDINGS: 176 articles from 24 countries were included in our analysis of antibiotic resistance. The overall mean prevalences of primary H pylori resistance were 17% (95% CI 15-18) for clarithromycin, 44% (95% CI 39-48) for metronidazole, 18% (95% CI 15-22) for levofloxacin, 3% (95% CI 2-5) for amoxicillin, and 4% (95% CI 2-5) for tetracycline. Prevalence of resistance to clarithromycin and levofloxacin rose significantly over time during the period investigated, whereas resistance to other antibiotics remained stable. 170 articles from 16 countries were included in analysis of efficacy of first-line therapies. We noted unsatisfactory efficacy (ie, <80%) with clarithromycin-containing regimens in countries where the clarithromycin resistance rates were higher than 20%.
INTERPRETATION: The prevalence of primary antibiotic resistance varied greatly among countries in the Asia-Pacific region, and thus treatment strategy should be adapted relative to country-specific resistance patterns. Clarithromycin-containing regimens should be avoided in countries where the prevalence of clarithromycin resistance is higher than 20%.
FUNDING: Ministry of Health and Welfare of Taiwan, Ministry of Science and Technology of Taiwan, and Amity University.
METHODS: A total of 210 Aeromonas clinical isolates were investigated: 116 from Singapore General Hospital and 94 archived clinical isolates from University of Malaya Medical Center, Malaysia. The isolates were genetically identified based on the gcat gene screening and the partial sequences of the rpoD housekeeping gene. Genetic relatedness, distribution of 15 virulence genes and 4 beta-lactamase resistance genes, and susceptibility patterns to 11 antimicrobial agents were compared.
RESULTS: Of the 210 Aeromonas isolates, A. dhakensis-94 (45%) was the dominant species in Singapore and Malaysia. Species composition was similar and enterobacterial repetitive intergenic consensus-PCR did not show genetic relatedness between strains from the two countries. Of the 15 virulence genes, A. dhakensis and A. hydrophila harbored the most compared with other species. Different combinations of 9 virulence genes (exu, fla, lip, eno, alt, dam, hlyA, aexU, and ascV) were present in A. dhakensis, A. hydrophila, and A. veronii from both the countries. Distribution of virulence genes was species and anatomic site related. Majority (>80%) of the strains were susceptible to all antimicrobial agents tested, except amoxicillin and cephalothin. A. dhakensis strains from Malaysia significantly harbored the cphA gene compared with A. dhakensis from Singapore. Multidrug resistance was mostly detected in strains from peritoneal fluids of dialysis patients.
CONCLUSION: This study revealed A. dhakensis as the dominant species isolated in both geographic regions, and that it carried a high number of virulence genes. It also highlights the geographic-related differences of virulence gene distribution and antimicrobial resistance profiles of clinical Aeromonas strains from Singapore and Malaysia.
DATA SOURCES: A PubMed search was completed in Clinical Queries using the key terms "Staphylococcal scalded skin syndrome" and "Ritter disease".
RESULTS: SSSS is caused by toxigenic strains of Staphylococcus aureus. Hydrolysis of the amino-terminal extracellular domain of desmoglein 1 by staphylococcal exfoliative toxins results in disruption of keratinocytes adhesion and cleavage within the stratum granulosum which leads to bulla formation. The diagnosis is mainly clinical, based on the findings of tender erythroderma, bullae, and desquamation with a scalded appearance especially in friction zones, periorificial scabs/crusting, positive Nikolsky sign, and absence of mucosal involvement. Prompt empiric treatment with intravenous anti-staphylococcal antibiotic such as nafcillin, oxacillin, or flucloxacillin is essential until cultures are available to guide therapy. Clarithromycin or cefuroxime may be used should the patient have penicillin allergy. If the patient is not improving, critically ill, or in communities where the prevalence of methicillin-resistant S. aureus is high, vancomycin should be used.
CONCLUSION: A high index of suspicion is essential for an accurate diagnosis to be made and treatment promptly initiated.