Antimicrobial resistance among common bacterial pathogens in Indonesia: a systematic review.

Background: The WHO Global Antimicrobial Resistance Surveillance System (GLASS) aims to describe antimicrobial resistance (AMR) patterns and trends in common bacterial pathogens, but data remain limited in many low and middle-income countries including Indonesia. Methods: We systematically searched Embase, PubMed and Global Health Database and three Indonesian databases for original peer-reviewed articles in English and Indonesian, published between January 1, 2000 and May 25, 2023, that reported antimicrobial susceptibility for the 12 GLASS target pathogens from human samples. Pooled AMR prevalence estimates were calculated for relevant pathogen-antimicrobial combinations accounting for the sampling weights of the studies (PROSPERO: CRD42019155379). Findings: Of 2182 search hits, we included 102 papers, comprising 19,517 bacterial isolates from hospitals (13,647) and communities (5870). In hospital settings, 21.6% of Klebsiella pneumoniae isolates, 18.3% of Escherichia coli isolates, 35.8% of Pseudomonas aeruginosa isolates and 70.7% of Acinetobacter baumannii isolates were carbapenem-resistant; 29.9% of Streptococcus pneumoniae isolates were penicillin-resistant; and 22.2% of Staphylococcus aureus isolates were methicillin-resistant. Hospital prevalence of carbapenem-resistant K. pneumoniae and E. coli, and penicillin-resistant S. pneumoniae increased over time. In communities, 28.3% of K. pneumoniae isolates and 15.7% of E. coli isolates were carbapenem-resistant, 23.9% of S. pneumoniae isolates were penicillin-resistant, and 11.1% of S. aureus isolates were methicillin-resistant. Data were limited for the other pathogens. Interpretation: AMR prevalence estimates were high for critical gram-negative bacteria. However, data were insufficient to draw robust conclusions about the full contemporary AMR situation in Indonesia. Implementation of national AMR surveillance is a priority to address these gaps and inform context-specific interventions. Funding: Wellcome Africa Asia Programme Vietnam.

Evaluation of SARS-CoV-2 quantification from oropharyngeal swabs, nasopharyngeal swabs, and naso-oropharyngeal swabs: A cross-sectional study.

The current naso-oropharyngeal swab for SARS-CoV-2 detection faces several problems, such as waste issues and its use for quantitative studies. This study aimed to evaluate the total RNA and viral loads from different upper respiratory tract swabs types and whether SARS-CoV-2 quantification can use the current internal control for normalization. This cross-sectional study collected positive specimens with single oropharyngeal or nasopharyngeal swabs and naso-oropharyngeal swabs. The samples were extracted, tested with qualitative RT‒PCR, and then tested with quantitative RT‒PCR. The RNA eluate was measured for the total RNA concentration. The total RNA concentration, viral load, and RNaseP Ct values were collected and analysed statistically. The positive results came from 41 oropharyngeal swabs, 34 nasopharyngeal swabs, and 36 naso-oropharyngeal swabs. The total RNA increased significantly from oropharyngeal swabs to nasopharyngeal swabs to naso-oropharyngeal swabs. Significant differences in RNaseP Ct values between groups and their correlations with total RNA were found. In addition, the increase in the total RNA and the RNaseP Ct values were unrelated to the viral load. The physical features in the naso-oropharyngeal area and the swabbing procedures could affect the total RNA but not the viral load. However, since the virus particles could present inside and outside human cells, the increase in collected human cells may not always be followed by the viral load increase. Normalization using the RNaseP Ct value became unnecessary due to the factors mentioned above. Therefore, a careful approach is needed in viral load studies of swab specimens.

COVID-19 Screening Score for Patients without Acute Respiratory Symptoms Undergoing Emergency Medical Procedures in Indonesia.

To rule out coronavirus disease-2019 (COVID-19) in patients scheduled to undergo emergency medical procedures, SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) must be performed. In developing countries, the use of SARS-CoV-2 RT-PCR has been limited by its unavailability and long processing time. Hence, a quick screening score to predict COVID-19 may help healthcare practitioners determine which patients without acute respiratory symptoms can safely undergo an emergency medical procedure. We conducted a cross-sectional study of adult patients without acute respiratory symptoms who were admitted to the emergency department and underwent an emergency medical procedure within 24 hours after admittance. We collected baseline demographic data, COVID-19 screening variables, and SARS-CoV-2 RT-PCR as the gold standard for COVID-19 diagnosis. Bivariate and multivariate analyses were performed, and a scoring system was developed using statistically significant variables from the multivariate analysis. With data from 357 patients, multivariate backward stepwise logistic regression analysis resulted in two significant COVID-19 predictors: the presence of SARS-CoV-2-IgM antibody (adjusted odds ratio [aOR]: 7.02 [95% CI: 1.49-32.96]) and typical chest x-ray (aOR: 23.21 [95% CI: 10.01-53.78]). A scoring system was developed using these predictors with an area under the receiver operating characteristic curve of 0.71 (95% CI: 0.64-0.78). For a cutoff point of ≥ 2, the scoring system showed 42.5% sensitivity and 97.1% specificity but had poor calibration (Hosmer-Lemeshow test P value < 0.001). We believe that the development of this COVID-19 quick screening score may be helpful in a resource-limited clinical setting, but its moderate discrimination and poor calibration hinder its use as a replacement for the SARS-CoV-2 RT-PCR test for COVID-19 screening.

Application of a sepsis flow chip (SFC) assay for the molecular diagnosis of paediatric sepsis.

A delay in detecting sepsis pathogens is a problematic issue for determining definitive antibiotic therapy for the causative pathogens. The gold standard method for sepsis is blood culture but this requires 3 days to detect the definitive pathogen. Molecular methods offer rapid identification of pathogens. We evaluated the use of sepsis flow chip (SFC) assay for identifying pathogens from children with sepsis. Blood samples from children with sepsis were collected and incubated in a culture device. Positive samples were subjected to amplification-hybridization using SFC assay and culture. A total of 94 samples from 47 patients were recovered, from which 25 isolates were recovered, including Klebsiella pneumoniae (11) and Staphylococcus epidermidis (6). From 25 positive blood culture bottles subjected to SFC assay, 24 genus/species and 18 resistance genes were detected. The sensitivity, specificity and conformity was 80, 94.2 and 94.68 % respectively. SFC assay offers promise to identify pathogens from positive blood culture in paediatric patients with sepsis and may support the antimicrobial stewardship programme in hospitals.

Whole Genome Multi-Locus Sequence Typing and Genomic Single Nucleotide Polymorphism Analysis for Epidemiological Typing of Pseudomonas aeruginosa From Indonesian Intensive Care Units.

We have previously studied carbapenem non-susceptible Pseudomonas aeruginosa (CNPA) strains from intensive care units (ICUs) in a referral hospital in Jakarta, Indonesia (Pelegrin et al., 2019). We documented that CNPA transmissions and acquisitions among patients were variable over time and that these were not significantly reduced by a set of infection control measures. Three high risk international CNPA clones (sequence type (ST)235, ST823, ST357) dominated, and carbapenem resistance was due to carbapenemase-encoding genes and mutations in the porin OprD. Pelegrin et al. (2019) reported core genome analysis of these strains. We present a more refined and detailed whole genome-based analysis of major clones represented in the same dataset. As per our knowledge, this is the first study reporting Single Nucleotide Polymorphisms (wgSNP) analysis of Pseudomonas strains. With whole genome-based Multi Locus Sequence Typing (wgMLST) of the 3 CNPA clones (ST235, ST357 and ST823), three to eleven subgroups with up to 200 allelic variants were observed for each of the CNPA clones. Furthermore, we analyzed these CNPA clone clusters for the presence of wgSNP to redefine CNPA transmission events during hospitalization. A maximum number 35350 SNPs (including non-informative wgSNPs) and 398 SNPs (ST-specific_informative-wgSNPs) were found in ST235, 34,570 SNPs (including non-informative wgSNPs) and 111 SNPs (ST-specific_informative-wgSNPs) in ST357 and 26,443 SNPs (including non-informative SNPs) and 61 SNPs (ST-specific_informative-wgSNPs) in ST823. ST-specific_Informative-wgSNPs were commonly noticed in sensor-response regulator genes. However, the majority of non-informative wgSNPs was found in conserved hypothetical proteins or in uncharacterized proteins. Of note, antibiotic resistance and virulence genes segregated according to the wgSNP analyses. A total of 8 transmission chains for ST235 strains followed by 9 and 4 possible transmission chains for ST357 and ST823 were traceable on the basis of pairwise distances of informative-wgSNPs (0 to 4 SNPs) among the strains. The present study demonstrates the value of detailed whole genome sequence analysis for highly refined epidemiological analysis of P. aeruginosa.

Distribution of Carbapenemase Genes among Carbapenem-Non-Susceptible Acinetobacter baumanii Blood Isolates in Indonesia: A Multicenter Study.

Carbapenem non-susceptible Acinetobacter baumannii (CNSAB) is an important pathogen that causes nosocomial bacteremia among critically ill patients worldwide. The magnitude of antibiotic resistance of A. baumanii in Indonesia is expected to be significant; however, the data available are limited. The aim of this study was to analyze the genetic profiles of CNSAB isolates from patients with bacteremia in Indonesia. CNSAB isolates from blood cultures of bacteremia patients in 12 hospitals in Indonesia were included. The blood cultures were conducted using the BacT/Alert or BACTEC automated system. The CNSAB were identified with either Vitek 2 system or Phoenix platform followed by a confirmation test using a multiplex polymerase chain reaction (PCR) assay, targeting the specific gyrB gene. The carbapenemase genes were detected by multiplex PCR. In total, 110 CNSAB isolates were collected and were mostly resistant to nearly all antibiotic classes. The majority of CNSAB isolates were susceptible to tigecycline and trimethoprim-sulfamethoxazole (TMP-SMX), 45.5% and 38.2%, respectively. The blaOXA-51-like gene was identified in all CNSAB isolates. Out of the total, 83.6% of CNSAB isolates had blaOXA-23-like gene, 37.3% blaOXA-24-like gene, 4.5% blaNDM-1 gene, 0.9% blaIMP-1 gene, and 0.9% blaVIM gene. No blaOXA-48-like gene was identified. The blaOXA-23-like gene was the predominant gene in all except two hospitals. The presence of the blaOXA-24-like gene was associated with resistance to tigecycline, amikacin, TMP-SMX and cefoperazone-sulbactam, while blaOXA-23-like gene was associated with resistance to TMP-SMX and cefoperazone-sulbactam. In conclusion, the blaOXA-23-like gene was the predominant gene among CNSAB isolates throughout Indonesia. A continuous national surveillance system needs to be established to further monitor the genetic profiles of CNSAB in Indonesia.

Multimodal intervention to reduce acquisition of carbapenem-non-susceptible Gram-negative bacteria in intensive care units in the National Referral Hospital of Indonesia: An interrupted time series study.

PURPOSE: To evaluate a low-cost multimodal intervention on the acquisition of carbapenem-non-susceptible Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa by patients in low-resource intensive care units. MATERIALS AND METHODS: We performed a quasi-experimental study in a referral hospital in Jakarta, Indonesia: pre-intervention phase 1 (2013-2014), intervention phase 2 (2014-2015) and post-intervention phase 3 (2015-2016). The intervention was hand hygiene promotion and environmental cleaning and disinfection combined with patient disinfection and cohorting. The primary outcome was acquisition of resistant bacteria per 100 patient-days at risk, which was assessed by active microbiological surveillance and analysed with a multilevel Poisson segmented regression model. RESULTS: In phase 1 (387 patients), the acquisition rate was 4.3/100 days for carbapenem-non-susceptible A. baumannii versus 1.1/100 days for both K. pneumoniae and P. aeruginosa. There was a significant step change from phase 1 to phase 3 (361 patients) in the acquisition of carbapenem-non-susceptible strains, the incidence rate ratio (IRR) was 0.343 (99%CI: 0.164-0.717). This significant change was mainly due to reduced acquisitions of resistant A. baumannii (IRR 0.4, 99%CI: 0.181-1.061). Negative confounding was observed. CONCLUSION: A multimodal intervention to prevent acquisition of resistant pathogens is feasible and may be effective in ICUs in lower-middle income countries.

Consideration of the Cycle Threshold Values from Real-Time RT-PCR SARS-CoV-2 Interpretation for the Clinicians: Analysis of 339 Positive Cases from a Referral Laboratory in Jakarta, Indonesia.

BACKGROUND: real-time RT-PCR was recommended by WHO for COVID-19 diagnosis. The cycle threshold (Ct) values were expected to have an association with clinical manifestation. However, the diagnostic modalities such as quantitative molecular detection and virus isolation were not yet available for the routine test. This study has been conducted to analyze the relationship between the Ct values of qualitative rRT-PCR and the clinical manifestation and to describe the factors determining the result. METHODS: from March to April 2020, specimens were sent to our laboratory from different healthcare centers in Jakarta. The patient's characteristic and clinical manifestation were extracted from the specimen's epidemiology forms. The specimens extracted and tested using rRT-PCR, and the Ct value were collected. The data were analyzed using the appropriate statistic test. RESULTS: from 339 positive results, the mild to moderate case was 176 (52%) and the severe cases was 163 (48%). Female was dominant in the mild to moderate cases (58%), while the male was prevalent in the severe cases (60%). The median age for mild to moderate case was 35 years old and severe cases was 49 years old. Statistical analysis found relationship between both group with gender (p = 0.001) and age (p < 0.001), but not with the Ct value. CONCLUSION: many variables in specimen sampling and processing could affect the Ct value result. In addition, the disease's severity was depended with the host immune response, regardless the number of virus. There was suggested no significant difference between the Ct values of mild-moderate and severe COVID-19, and thus should not be loosely interpreted.

Infections and antimicrobial resistance in intensive care units in lower-middle income countries: a scoping review.

BACKGROUND: Intensive care units (ICUs) in lower-middle income countries (LMICs) are suspected to constitute a special risk for patients of acquiring infection due to multiple antibiotic resistant organisms. The aim of this systematic scoping review was to present the data published on ICU-acquired infections and on antimicrobial resistance observed in ICUs in LMICs over a 13-year period. A systematic scoping review was conducted according to the PRISMA extension guideline for scoping reviews and registered in the Open Science Framework. Articles were sought that reported on ICU-acquired infection in LMICs between 2005 and 2018. Two reviewers parallelly reviewed 1961 titles and abstracts retrieved from five data banks, found 274 eligible and finally included 51. Most LMICs had not produced reports in Q1 or Q2 journals in this period, constituting a large gap in knowledge. However, from the reported evidence it is clear that the rate of ICU-acquired infections was comparable, albeit approximately 10% higher, in LMICs compared to high income countries. In contrast, ICU mortality was much higher in LMICs (33.6%) than in high income countries (< 20%). Multidrug-resistant Gram-negative species, especially Acinetobacter baumannii and Pseudomonas aeruginosa, and Klebsiella pneumoniae played a much more dominant role in LMIC ICUs than in those in high income countries. However, interventions to improve this situation have been shown to be feasible and effective, even cost-effective. CONCLUSIONS: Compared to high income countries the burden of ICU-acquired infection is higher in LMICs, as is the level of antimicrobial resistance; the pathogen distribution is also different. However, there is evidence that interventions are feasible and may be quite effective in these settings. Protocol Registration The protocol was registered with Open Science Framework ( https://osf.io/c8vjk ).

Clinical impact of endemic NDM-producing Klebsiella pneumoniae in intensive care units of the national referral hospital in Jakarta, Indonesia.

OBJECTIVE: A prospective observational study was performed to assess the epidemiology and clinical impact of carbapenem-non-susceptible Klebsiella pneumoniae (CNKP) in intensive care units (ICUs) of the national referral hospital in Jakarta, Indonesia. MATERIALS/METHODS: Adult patients consecutively hospitalized for > 48 h in two ICUs of the national referral hospital were included from April until October 2013 and from April until August 2014. K. pneumoniae from clinical cultures and standardized screening of rectum and throat on admission, discharge and weekly if hospitalized > 7 days were collected. Environmental niches and healthcare workers (HCWs) were also screened. Susceptibility was determined phenotypically and the presence of carbapenemase genes by PCR. Raman spectroscopy as well as multiple-locus variable number tandem repeat analysis (MLVA) were used for typing. RESULTS: Twenty-two out of 412 (5.3%) patients carried CNKP on admission and 37/390 (9.5%) acquired CNKP during ICU stay. The acquisition rate was 24.7/1000 patient-days at risk. One out of 31 (3.2%) environmental isolates was a CNKP. None of the HCWs carried CNKP. Acquisition of CNKP was associated with longer ICU stay (adjusted Hazard Ratio: 2.32 [CI99: 1.35-3.68]). ICU survival was lower among patients with CNKP compared to patients with carbapenem-susceptible K. pneumoniae (aHR 2.57, p = 0.005). Ninety-six of the 100 (96%) CNKP isolates carried a carbapenemase gene, predominantly blaNDM. Raman typing revealed three major clusters among 48 Raman types identified, whereas MLVA distinguished six major clusters among a total of 30 different genotypes. CONCLUSIONS: NDM-producing CNKP are introduced into these ICUs and some strains expand clonally among patients and the environment, resulting in endemic CNKP. CNKP acquisition was associated with prolonged ICU stay and may affect ICU survival. TRIAL REGISTRATION: The study was registered at Netherlands Trial Register http://www.trialregister.nl. Candidate number: 23527, NTR number: NTR5541, NL number: NL5425 (https://www.trialregister.nl/trial/5424), Retrospectively registered: NTR: 22 December 2015.

High-Risk International Clones of Carbapenem-Nonsusceptible Pseudomonas aeruginosa Endemic to Indonesian Intensive Care Units: Impact of a Multifaceted Infection Control Intervention Analyzed at the Genomic Level.

Infection control effectiveness evaluations require detailed epidemiological and microbiological data. We analyzed the genomic profiles of carbapenem-nonsusceptible Pseudomonas aeruginosa (CNPA) strains collected from two intensive care units (ICUs) in the national referral hospital in Jakarta, Indonesia, where a multifaceted infection control intervention was applied. We used clinical data combined with whole-genome sequencing (WGS) of systematically collected CNPA to infer the transmission dynamics of CNPA strains and to characterize their resistome. We found that the number of CNPA transmissions and acquisitions by patients was highly variable over time but that, overall, the rates were not significantly reduced by the intervention. Environmental sources were involved in these transmissions and acquisitions. Four high-risk international CNPA clones (ST235, ST823, ST357, and ST446) dominated, but the distribution of these clones changed significantly after the intervention was implemented. Using resistome analysis, carbapenem resistance was explained by the presence of various carbapenemase-encoding genes (blaGES-5, blaVIM-2-8, and blaIMP-1-7-43) and by mutations within the porin OprD. Our results reveal for the first time the dynamics of P. aeruginosa antimicrobial resistance (AMR) profiles in Indonesia and additionally show the utility of WGS in combination with clinical data to evaluate the impact of an infection control intervention. (This study has been registered at www.trialregister.nl under registration no. NTR5541).IMPORTANCE In low-to-middle-income countries such as Indonesia, work in intensive care units (ICUs) can be hampered by lack of resources. Conducting large epidemiological studies in such settings using genomic tools is rather challenging. Still, we were able to systematically study the transmissions of carbapenem-nonsusceptible strains of P. aeruginosa (CNPA) within and between ICUs, before and after an infection control intervention. Our data show the importance of the broad dissemination of the internationally recognized CNPA clones, the relevance of environmental reservoirs, and the mixed effects of the implemented intervention; it led to a profound change in the clonal make-up of CNPA, but it did not reduce the patients' risk of CNPA acquisitions. Thus, CNPA epidemiology in Indonesian ICUs is part of a global expansion of multiple CNPA clones that remains difficult to control by infection prevention measures.

Epidemiology and characterisation of carbapenem-non-susceptible Pseudomonas aeruginosa in a large intensive care unit in Jakarta, Indonesia.

The aim of this study was to describe the epidemiology and clinical impact of carbapenem-non-susceptible Pseudomonas aeruginosa (CNPA) in intensive care units (ICUs) of the national referral hospital of Indonesia. Adult patients admitted to ICUs were prospectively included. Pseudomonas aeruginosa were from clinical cultures and systematic screening. Environmental niches and healthcare workers (HCWs) were also screened. Susceptibility was determined phenotypically and the presence of carbapenemase genes was determined by PCR. Multiple loci variable-number tandem repeat analysis (MLVA) and multilocus sequence typing (MLST) were used for genotyping. Of the patients included in the study, 17/412 (4.1%) carried CNPA on admission and 34/395 (8.6%) became positive during their ICU stay. The acquisition rate was 18/1000 patient-days at risk. Of 16 environmental isolates, 12 (75.0%) were CNPA. HCWs screened negative. Acquisition of CNPA was associated with longer ICU stay (adjusted hazard ratio = 1.89, 99% confidence interval 1.12-3.13). Mortality was >40% among patients with CNPA versus <30% among those without CNPA (P = 0.019). Moreover, 83/119 (69.7%) CNPA carried either blaVIM (n = 36), blaIMP (n = 23) or blaGES-5 (n = 24). Four sequence types (STs) dominated (ST235, ST823, ST446 and ST357). Five major MLVA clusters were distinguished, two belonging to ST235 and the other three to ST823, ST446 and ST357. CNPA are introduced into these ICUs and some strains expand clonally among patients and the environment, creating endemic CNPA. VIM-, IMP- and GES-5 genes are prevalent. CNPA acquisition was associated with prolonged ICU stay and may affect ICU survival.

A multifaceted hand hygiene improvement program on the intensive care units of the National Referral Hospital of Indonesia in Jakarta.

Background: Hand hygiene (HH) is considered to be the single most effective measure in preventing healthcare-associated infections. However, HH compliance rates among nurses and doctors in hospitals are often very low. Few studies have addressed HH compliance in Indonesia, performed interventions to increase HH compliance, and none have had long-term follow-up. We, therefore, addressed this issue by performing long-term follow-up after a multifaceted intervention in the intensive care unit (ICU) setting. Methods: This was an observational, prospective, before-and-after intervention study (May-September 2014, February-April 2017). We measured HH knowledge and HH compliance before (at baseline) and directly after a multifaceted improvement program (post-intervention) and performed a re-evaluation three years later. The multifaceted improvement program included education, feedback, reminders, interviews and the use of role models. The study involved nurses and physicians working in two ICUs of the Dr. Cipto Mangunkusumo Hospital in Jakarta. Results: A total of 97 at baseline, and 72 at post-intervention HH knowledge questionnaires were completed. There was a statistically significant improvement in the median overall HH knowledge score at post-intervention (from 15 to 22, p < 0.001). There was no significant difference between the two ICUs. The overall HH compliance was 27% at baseline and significantly improved to 77% post-intervention (p < 0.001). For all five HH moments, the compliance of nurses and physicians separately improved significantly from the baseline phase to the post-intervention phase (p < 0.001), except for 'moment 3' (after body fluid exposure), for which baseline rates were already high. Most of the compliance rates were significantly lower in both groups of healthcare workers upon follow-up three years later. Overall, the HH compliance of the nurses was significantly better than the physicians' compliance (p = 0.005). Conclusions: Our multifaceted improvement program, for nurses and physicians of the ICUs in the largest hospital of Indonesia, resulted in a significant improvement of the HH knowledge and HH compliance, but HH compliance levels waned over time after the intervention, indicating a need for continued monitoring and repeated interventions. Trial registration: The study was registered at www.trialregister.nl (No: 5541). Candidate number: 23527, NTR number: NTR5541, Date registered NTR: 22-DECEMBER-2015.

Endemic carbapenem-nonsusceptible Acinetobacter baumannii-calcoaceticus complex in intensive care units of the national referral hospital in Jakarta, Indonesia.

Background: Carbapenem-nonsusceptible A. baumannii-calcoaceticus complex have emerged worldwide, but the epidemiology in Indonesian hospitals has not been studied. Methods: A prospective observational study was performed on the intensive care units (ICUs) of the national referral hospital in Jakarta-Indonesia, in 2013 and 2014. All consecutive adult patients admitted and hospitalized for >48 h in ICUs were included. Basic and clinical data at admission were recorded. Carbapenem-nonsusceptible A. baumannii-calcoaceticus complex from clinical cultures and standardized screening were included. Environmental niches and healthcare workers (HCWs) were also screened. PCR was used to detect carbapenemase genes, and Raman spectroscopy as well as multilocus sequence typing (MLST) for typing. Results: Of 412 included patients, 69 (16.7%) carried carbapenem-nonsusceptible A. baumannii-calcoaceticus complex on admission, and 89 (25.9%) became positive during ICU stay. The acquisition rate was 43 per 1000 patient-days at risk. Six isolates were cultured from environment and one from a HCW. Acquisition of carbapenem-nonsusceptible A. baumannii-calcoaceticus complex was associated with longer ICU stay (median interquartile range [IQR]: 11 days [5-18], adjusted hazard ratio [aHR]: 2.56 [99% confidence interval (CI):1.76-3.70]), but not with mortality (adjusted odds ratio: 1.59 [99%CI: 0.74-3.40] at the chosen level of significance). The blaOXA-23-like gene was detected in 292/318 (91.8%) isolates, including isolates from the environment and HCW. Typing revealed five major clusters. Sequence types (ST)195, ST208, ST218, ST642 as well as new STs were found. The dominant clone consisted of isolates from patients and environment throughout the study period. Conclusions: Carbapenem-nonsusceptible A. baumannii-calcoaceticus complex are endemic in this setting. Prevention requires source control and limiting transmission of strains. Trial registration: The study was retrospectively registered at www.trialregister.nl (No:5541). Candidate number: 23,527, NTR number: NTR5541, Date registered NTR: 22nd December 2015.

Efficacy of Intravitreal Levofloxacin 0.5% Ophthalmic Solution in Treating Pseudomonas Aeruginosa Endophthalmitis on a Rabbit Model.

PURPOSE: To evaluate the efficacy of intravitreal levofloxacin 0.5% ophthalmic solution as treatment of Pseudomonas aeruginosa endophthalmitis in a rabbit model. DESIGN: This is a parallel randomized experimental study. METHODS: Twenty-six New Zealand white rabbits were enrolled. P. aeruginosa was inoculated intravitreally on the right eyes of all rabbits, which were further categorized into 2 groups, the treatment group (Group A) receiving 0.1 mL intravitreal injection levofloxacin 0.5% 24 hours after inoculation and the control group (Group B), which had 0.1 mL intravitreal aqua destilata (placebo). Clinical observation of the eyes in each group was performed on the first until the sixth day after the inoculation using clinical grading scale. On the sixth day, the eyes were examined for microbiological and histopathologic evaluations. RESULTS: The total clinical grading scores of each group were similar 24 hours after P. aeruginosa inoculation (P > 0.05). The total clinical grading scores of Group A on the sixth day and the difference in total clinical scores on the first and the sixth day were shown to be significantly lower than that of Group B (P < 0.05). Microbiological analysis revealed that there was a lower bacterial count in Group A (mean = 1.18 ± 0.93 logCFU/0.1 mL) compared with Group B (mean = 4.09 ± 1.51 logCFU/0.1 mL), and the histopathologic scores of both groups were also significantly different (P < 0.05). CONCLUSIONS: Intravitreal levofloxacin 0.5% ophthalmic solution at 0.1 mL dose appeared to be effective in treating P. aeruginosa endophthalmitis in rabbits.