Indonesia Pdf Novel

[Faith Lienhard]

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SAVAGE SON explores the dark side of man, incorporating much of what I experienced as both the hunter and hunted in Iraq and Afghanistan. By experienced, I do not mean simply the art and science of manhunting, but rather the emotions attached to building a pattern of life on a targeted individual and then executing the mission to capture or kill him. Also woven into the fabric of the story are the feelings associated with being the hunted; what it feels like to be on the receiving end of the ambush.

Though a completely fictional novel, if the emotions and feelings the protagonist experiences through the course of the narrative ring true, that is because they come from a real place. They come from my experience hunting the most dangerous of game.

Information regarding Helicobacter pylori antibiotic resistance in Indonesia was previously inadequate. We assessed antibiotic susceptibility for H. pylori in Indonesia, and determined the association between virulence genes or genetic mutations and antibiotic resistance. We recruited 849 dyspeptic patients who underwent endoscopy in 11 cities in Indonesia. E-test was used to determine the minimum inhibitory concentration of five antibiotics. PCR-based sequencing assessed mutations in 23S rRNA, rdxA, gyrA, gyrB, and virulence genes. Next generation sequencing was used to obtain full-length sequences of 23S rRNA, infB, and rpl22. We cultured 77 strains and identified 9.1% with clarithromycin resistance. Low prevalence was also found for amoxicillin and tetracycline resistance (5.2% and 2.6%, respectively). In contrast, high resistance rates to metronidazole (46.7%) and levofloxacin (31.2%) were demonstrated. Strains isolated from Sumatera Island had significantly higher metronidazole resistance than those from other locations. Metronidazole resistant strains had highly distributed rdxA amino acid substitutions and the 23S rRNA A2143G mutation was associated with clarithromycin resistance (42.9%). However, one strain with the highest MIC value had a novel mutation in rpl22 without an A2143G mutation. Mutation at Asn-87 and/or Asp-91 of gyrA was associated with levofloxacin-resistance and was related to gyrB mutations. In conclusions, although this is a pilot study for a larger survey, our current data show that Indonesian strains had the high prevalence of metronidazole and levofloxacin resistance with low prevalence of clarithromycin, amoxicillin, and tetracycline resistance. Nevertheless, clarithromycin- or metronidazole-based triple therapy should be administered with caution in some regions of Indonesia.

Copyright: 2016 Miftahussurur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

The understanding of H. pylori antibiotic resistance mechanisms, which primarily occur because of mutations in chromosomal genes, is important as a premise for the establishment of rational antibiotic combinations. Critically, although numerous point mutations have appeared, the positions of such mutations were not uniform for every topographical area [18,19]. For example, although two nucleotide substitutions, specifically, A2142G or A2142C and A2143G in the peptidyl transferase loop of 23S rRNA, cause primary CAM resistance in H. pylori strains isolated in Western countries [20], they account for only 23% of resistant strains in Asia [20]. Our previous report demonstrated the synergic effect of mutated sequences in hp1048 (infB), hp1314 (rpl22), and A2143G, which resulted in higher MICs [21]. Unlike the mutational patterns of 23S rRNA, the mechanisms of MNZ resistance are complex and largely associated with inactivating mutations in rdxA, through frameshift mutations, insertions, and deletions [22]. Moreover mutations in the sequences of gyrase subunit A (gyrA) and gyrB, encoding translational proteins, greatly reduce the antimicrobial ability of fluoroquinolones [23].

In this study, we aimed to determine the antibiotic susceptibility of H. pylori in 11 cities, covering the five largest islands, of Indonesia. We also analyzed the association between virulence genes and antibiotic resistance rates. Furthermore, we determined the presence of genetic mutations that are associated with antibiotic resistance.

We conducted a prospective study from August 2012 to November 2015. This study included 849 adult dyspeptic patients who underwent endoscopy examinations in 11 cities including cities on the five largest islands of Indonesia. Patients with bleeding related to esophageal varices, a history of partial gastric resection and previous H. pylori eradication therapy were excluded from this study. Included were patients from Surabaya (296 patients), Jakarta (31), and Malang (97) on Java Island, Aceh (38) and Medan (93) on Sumatera Island, Pontianak (90) on Kalimantan Island, Makassar (30) and Manado (57) on Sulawesi Island, Jayapura (21) on Papua Island, Bangli (61) on Bali Island, and Kupang (35) on Timor Island. Peptic ulcer diseases were diagnosed by endoscopic observation, whereas chronic gastritis was determined by histologic examination. All procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. There were no minors or children enrolled in our study, therefore not needed informed consent from the next of kin, caretakers, or guardians on behalf of them. Written informed consent was obtained from all participants, and the study protocol was approved by the Institutional Review Board or the Ethics Committee of Dr. Cipto Mangunkusumo Teaching Hospital (Jakarta, Indonesia), Dr. Soetomo Teaching Hospital (Surabaya, Indonesia), Dr. Wahidin Sudirohusodo Teaching Hospital (Makassar, Indonesia), and Oita University Faculty of Medicine (Yufu, Japan).

For H. pylori culture, antral biopsy specimens were homogenized and inoculated onto antibiotics selection plate, subsequently subcultured onto Mueller Hinton II Agar medium (Becton Dickinson, NJ, USA) supplemented with 10% horse blood without antibiotics. The plates were incubated for up to 10 days at 37C under microaerophilic conditions (10% O2, 5% CO2, and 85% N2). H. pylori isolates were identified based on colony morphology, Gram staining results, and positive reactions for oxidase, catalase, and urease. Isolated strains were stored at -80C in Brucella Broth (Difco, NJ, USA) containing 10% dimethyl sulfoxide and 10% horse serum.

The E-test method (Biomerieux, France) was used to determine the minimum inhibitory concentration (MIC) of AMX, MNZ, TCN, CAM, and LVX. Mueller-Hinton II Agar medium (Becton Dickinson) supplemented with 10% defibrinated horse blood was used as culture media. The bacterial suspension, adjusted to be equivalent to a McFarland opacity standard of 3.0, was inoculated onto the plates. After 72 h of incubation, the MIC of each antibiotic was determined. Quality control was performed using H. pylori ATCC 43504. The resistance breakpoints were determined as described by the European Committee on Antimicrobial Susceptibility Testing (EUCAST; available at ). Strains were considered to be resistant for MICs of >0.125 mg/L for AMX, 0.25 mg/L for CAM, 8 mg/L for MNZ, and 1 mg/L for TCN and LVX.

To find other genetic mutations, associated with high MIC values, but not involving typical 23S rRNA mutations, we also obtained full-length 23S rRNA, hp1048 (infB), and hp1314 (rpl22) [21] from next-generation sequencing data (MiSeq next-generation sequencer; Illumina, Inc., San Diego, CA). MiSeq output was integrated into contig sequences by CLC Genomics Workbench 7.0.4. Genomics Workbench was also used for gene prediction and translation to protein sequences.

Discrete variables were tested using the chi-square test, whereas continuous variables were tested using the Mann-Whitney U and t-tests. A multivariate logistic regression model was used to calculate the odds ratios (OR) of clinical outcomes including age, sex, H. pylori antibiotic resistance, ethnicity, and location. All determinants with P values The predominant ethnic groups from different islands and their association with antibiotic resistance rates are shown in Table 4. Strains isolated from Ambonese, Chinese, and Balinese individuals displayed a high prevalence of CAM resistance (50.0%, 20.0%, and 16.6%, respectively, Table 4).

Only those from Buginese individuals showed AMX resistance >15%. Among three ethnicities with the highest prevalence of H. pylori in Indonesia [12], Papuan and Batak individuals were associated with a large number of antibiotic resistance types, including LVX, which is part of a second-line regimen, in contrast to strains isolated from Buginese individuals. Ambonese individuals were associated with higher rates of MNZ and TCN resistance than other ethnicities (both P = 0.01). Only strains from Dayak individuals were sensitive to all five antibiotics.

No strain was resistant to all tested antibiotics (Table 5). Fifteen strains showed dual-drug resistance (11 strains for MNZ-LVX, two for CAM-LVX and one each for MNZ-AMX and LVX-AMX). Resistance to three antibiotics was observed in two (2.6%) strains that were isolated from Java Island; one was resistant to a combination of CAM, MNZ, and LVX. In addition, two strains (obtained from Sumatera and Java Island) were recognized as resistant to four drugs including LVX. Overall, Java (six strains) and Sumatera Island (seven strains) showed a higher prevalence of multidrug resistance than other locations. No differences were observed for clinical outcomes between single-drug and multidrug resistant infections (P = 0.53).

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