Efficacy and safety of co-trimoxazole in eradication phase of melioidosis; systematic review.

BACKGROUND: Melioidosis is an infectious disease caused by the bacterium Burkholderia pseudomallei. The two stages of melioidosis treatment are the intense intravenous phase and the oral eradication phase. Although co-trimoxazole has been in use for several years, the literature does not demonstrate uniformity of the drug doses, combinations, or durations suitable for the eradication phase of melioidosis. The safety profile of co-trimoxazole was not documented in the literature, nor have systematic studies of its effectiveness been done. This systematic review sought to study on the dose, duration and combination of co-trimoxazole therapy in view of clinical efficacy and safety in the eradication phase of melioidosis. MAIN BODY: This systematic review included all of the published articles that employed co-trimoxazole in the eradication phase after 1989, including, randomized clinical trials, case-control studies, cohorts, case reports, and case series. Throughout the eradication (maintenance) phase, co-trimoxazole usage was permissible in any dose for any period. A total of 40 results were included in the analysis which contained six clinical trials, one cohort study, one Cochrane review, and thirty-two case series/case reports. Clinical and microbial relapse rates are low when co-trimoxazole is used in single therapy than in combination. There were several adverse events of co-trimoxazole, however, a quantitative analysis was not conducted as the data did not include quantitative values in most studies. SHORT CONCLUSION: The dose of co-trimoxazole, duration of the eradication phase, and other combinations used in the treatment was varying between studies. Compared to combined therapy patients treated with co-trimoxazole alone the mortality and relapse rates were low. The lowest relapse rate and lowest mortality rate occur when using co-trimoxazole 1920 mg twice daily. The duration of therapy varies on the focus of melioidosis and it is ranged from 2 months to one year and minimum treatment duration associated with low relapse rate is 3 months. The use of co-trimoxazole over the maintenance phase of melioidosis is associated with clinical cure but has adverse effects.

Antimicrobial misuse in pediatric urinary tract infections: recurrences and renal scarring.

BACKGROUND: In children, urinary tract infection (UTI) is one of a common bacterial infection. This study was conducted to detect the uropathogen, antimicrobial susceptibility, pathogen associated with recurrences and renal scarring in children initially taken care from general practitioners and later presented to tertiary care. METHODS: Every inward UTI episode, culture and antimicrobial susceptibility was done while on past 6-month, history of infections and use of antimicrobials was collected using clinical records and demonstration of antimicrobials. Children with recurrent pyelonephritis was followed and in vitro bio film formation was assessed. RESULTS: Frequency of UTI was significantly high among infants (p = 0.03). Last 6-month, all (220) were exposed to antimicrobials. Cefixime was the commonly prescribed antimicrobial (p = 0.02). In current UTI episode, 64.5% (142/220) of children with UTI were consulted GPs' prior to seek treatment from tertiary care pediatric unit (p = 0.02). While on follow up child who developed UTI, found urine culture isolates were significantly shifted from E. coli and K. pneumoniae to extended spectrum of beta-lactamase (ESBL) E. coli and K. pneumoniae. Out of 208 participants, 36 of them had re-current pyelonephritis (R-PN). Renal scarring (RS) was detected in 22 out of 70 patients with pyelonephritis following dimercaptosuccinic acid scan. Following each episodes of recurrent pyelonephritis 11% of new scar formation was detected (p = 0.02). Bio film forming E. coli and K. pneumoniae was significantly associated in patients with R-PN (p = 0.04). DISCUSSION: Medical care providers often prescribe antimicrobials without having an etiological diagnosis. While continuing exposure of third generation cephalosporin and carbapenem leads to development of ESBL and CRE microbes in great. The empiric uses of antimicrobials need to be stream lined with local epidemiology and antimicrobial susceptibility pattern. R-PN in childhood leads to RS. In great, bio film formation act as the focus for such recurrences.

Development of neutropenic sepsis during the eradication phase with co-trimoxazole in patients with melioidosis: two case reports.

Introduction: Burkholderia pseudomallei is the bacterium that causes melioidosis. It is mostly a tropical disease, and particularly common in Southeast Asia and northern Australia. The intensive intravenous phase and the oral prolonged eradication phase are the two phases of melioidosis treatment. The current recommended treatment for melioidosis eradication is oral co-trimoxazole (TMP/SMX). Case report: Two patients were diagnosed with B. pseudomallei bacteremia without a focus and were treated with oral TMP/SMX with folic acid during the eradication phase. Both presented with neutropenic sepsis with pneumonia and pyelonephritis at days 48 and 45 following TMP/SMX 320/1600 mg q12h (4 tablets) and in both of them, the folic acid compliance was poor. One patient died and the other survived following intensive treatment for neutropenia. At the presentation following neutropenic sepsis among both patients, the red blood cells and platelets were within normal limits. Both patients were on a high dose of TMP/SMX, as both were within 40-60 kg of body weight the ideal TMP/SMX dose would be 240/1200 mg q12h (3 tablets). Pancytopenia caused by TMP/SMX can frequently develop gradually over time. Alternately, it can develop rapidly and swiftly escalate to fulminant sepsis, disseminated intravascular coagulation, and fast hemolysis. However, the development of isolated neutropenia is rarely described in the literature. Conclusions: Prolonged use of TMP/SMX is important to eradicate B. pseudomallei and always the possibility of rare adverse effects has to be considered. Always weight-based TMP-SMX dosing has to be encouraged with need to ensure the compliance of folic acid. During the eradication phase, continuous monitoring of blood cell lines with weekly full blood count would be essential to identify neutropenia in advance.

Use of high-dose ciprofloxacin for recurrent biofilm-forming multidrug-resistant Klebsiella pneumoniae bacteremia.

INTRODUCTION: Klebsiella pneumoniae is a significant nosocomial pathogen. We aimed to assess the clinical success following high-dose ciprofloxacin for recurrent bacteremia from biofilm-forming multidrug resistant Klebsiella pneumoniae in a liver transplanted patient. CASE REPORT: A 55-year-old male had undergone liver transplantation and at day 10 he developed fever and dysuria. Two blood cultures became positive and were identified by Vitek2 (BioMérieux, USA) as K. pneumoniae. From his urine K. pneumoniae was isolated. Based on antimicrobial susceptibility (AST) panel (Vitek2), i.v. meropenem 1 g 8 hourly and i.v. amikacin 15 mg/kg/ daily (5 days) were started (the isolate was ciprofloxacin-resistant). Following 14 days of meropenem he was discharged and 3 days later he was readmitted with fever and dysuria. Since the blood and urine isolate was K. pneumoniae, based on AST 21 days of meropenem were given, the patient was discharged and 3 days later he was readmitted with fever and dysuria. Since this was the 3rd episode with K. pneumoniae bacteremia, to exclude the focus of infection contrast-enhanced computed tomography and 18F-fluorodeoxyglucose-positron emission tomography were done but both were normal.Based on multilocus sequence typing (MLST) and microtiter plate assay, biofilm forming magA(K1)-positive (+) K. pneumoniae CC23 was found. The patient was having continuous asymptomatic bacteriuria with similar (magA(K1)-positive (+) K. pneumoniae CC23) isolate; we opted for high dose oral ciprofloxacin (800 mg, 8 hourly) for 7 days. CONCLUSIONS: Following a high dose of oral ciprofloxacin, we were able to achieve urinary microbial clearance and a permanent cure following (magA(K1)-positive (+) K. pneumoniae CC23) bacteremia. This could be a promising therapy to achieve microbial clearance from biofilm-forming multidrug-resistant K. pneumoniae.

The relationship between the exposure to healthcare settings and colonization with methicillin-resistant Staphylococcus aureus among medical students.

INTRODUCTION: Medical students who engage in clinical learning in healthcare settings can be potential methicillin-resistant Staphylococcus aureus (MRSA) carriers. METHODS: This is a descriptive cross-sectional study having a follow-up approach. Three batches of medical students who were studying at the Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka (1st, 3rd and 5th study years of MBBS course) were screened for nasal and axillary MRSA colonization. The first-year students were screened before and 6 months after clinical learning. The knowledge of the students about infection control was scored (percentage) using a questionnaire in the one week before and later one year after the hospital exposure. Data was compared using two-sample t test. RESULTS: The percentage of MRSA colonization was 6.36% (7/110) and 49.57% (59/119) before clinical exposure and after 2.5 years of exposure, respectively (p<0.012). The percentage of correct responses obtained by the students for the questionnaire about infection control was 28% and 66.9% one week before the exposure to the hospitals and one year after the exposure to the hospitals, consecutively. CONCLUSIONS: MRSA carriage was significantly associated with the time duration of the clinical training of the medical students. The knowledge of students about infection control was significantly inadequate one week before the hospital exposure and they have gained the knowledge only after being exposed to the hospitals.

Influence of early postoperative showering in undressed surgical wound for better clinical outcome.

Surgeons instruct the patients to avoid postoperative bathing and dress the wounds until the sutures are removed. All wounds were sutured at the end of surgery and kept undressed. Participants received a tap water body bath where the water covered the wound after 24h of surgery. The control group were asked not to wet the dressed surgical site until wound inspection on days 3 and 5. The patients were followed up in the surgery clinic on days 14 and 30 after surgery, when age, sex and type of surgery-matched controls' surgical site infection was significantly high in clean/contaminated and contaminated appendicectomy, breast lump excision, inguinal herniotomy and tendon repair surgeries. In contaminated appendicectomy, clean/contaminated and contaminated herniotomies postsurgical infections other than surgical site infection were significantly low in test groups. Early mobilisation, keeping the surgical wounds moist and providing a clean environment are suitable to minimise the surgical wound and other associated infections.

Childhood iron deficiency anemia leads to recurrent respiratory tract infections and gastroenteritis.

Anemia affects approximately 30% of children all over the world. Acute respiratory tract infections (ARTI), urinary tract infections (UTI) and gastroenteritis (GE) are common infectious entities in children. Here, we assessed the association between anemia and development of recurrent ARTI, UTI, and GE in children. This was a case-control study in hospitalized 2-5 years old children in Professorial Pediatric Unit at Teaching Hospital Anuradhapura, Sri Lanka. An 18-month follow up was done to assess the risk factors for the development of recurrent ARTI, GE, UTI, and control presented without infections. Further, 6-month follow up done after 3-month iron supplementation to assess the occurrence of recurrences. Blood Hb concentration was measured using Drabking's reagent. Logistic regression was used to find the risk factors for the development of recurrences. In ARTI, 121/165 (73.3%), GE, 88/124 (71%), UTI 46/96 (47.9%) and control 40/100 (40%) were having anemia. Initial ARTI group, recurrent ARTI was 24 (14.5%, p = 0.03); initial GE group: recurrent GE was 14 (11.3%, p = 0.03), recurrent ARTI was 11 (8.9%, p = 0.04); initial UTI group, development of; recurrent UTI was 8 (8.3%, p = 0.04); control, recurrent ARTI was 11 (11%, p = 0.03). Following 3-month iron supplementation reduction of recurrences was significant: initial ARTI recurrent ARTI in 90%, recurrent GE in 77.7%; initial GE recurrent GE in 83.3%, recurrent ARTI in 80%; initial UTI recurrent ARTI in 71.4% and control recurrent ARTI in 88.8%. Iron deficiency is a major type of anemia and anemic children are more prone to develop recurrent ARTI and GE. Once iron deficiency being corrected the rate of recurrent ARTI and GE was reduced. This would be a boost for policy developers to implement strategies at the community level to prevent iron deficiency in children to reduce ARTI and GE recurrences.

Assessment of healthiness among long term inhabiting army soldiers in dry zone of Sri Lanka.

OBJECTIVES: Military personnel, because of the unique nature of their duties, are reluctant to face stressors. Living in hot and humid conditions they frequently suffer dehydration. Army soldiers living in dry zone of Sri Lanka, were screened for chronic kidney disease (CKD), common non-communicable diseases and methicillin resistant Staphylococcus aureus (MRSA) colonization. Albumin creatinine ratio > 30 mg/g urine taken as cut-off for detection of CKD. RESULTS: Screened 417 soldiers, all were men and body mass index were 21.4 ± 2.2 kg/m2. They smoke 0.5 ± 0.1 pack years while consume alcohol 32 ± 3 units/week and were having 100/min average daily moderate physical activity. Eight of them (0.2%) were having essential hypertension, 4 (0.1%) of them were having diabetes mellitus. Blood cholesterol was within normal range. CKD unknown etiology (CKDu) prevalence among screened army soldiers was 0.009. All were from native army recruits. Further, 71.2% had MRSA colonization. In a group of middle aged army recruits, despite tobacco smoking and moderate level of alcohol consumption while continuously having healthy dietary practices with physical activities would leads to low prevalence of communicable diseases. Further, compared to native group of solders, visitors but living long time recruits CKDu incidence is zero.

Antibiotic resistance patterns of methicillin-resistant Staphylococcus aureus (MRSA) isolated from livestock and associated farmers in Anuradhapura, Sri Lanka.

INTRODUCTION: The animal husbandry comes to play an important role according to new economic reforms of the rural economy in South Asia including Sri Lanka, and the rural farming community has a poor knowledge about hygienic issues of animal husbandry, which can lead to spread of pathogenic bacterial strains from animals to humans. Our study was conducted to evaluate methicillin susceptible Staphylococcus aureus (MRSA) colonization and its antimicrobial resistance pattern among livestock (n=188) and related farmers (n=94) in Anuradhapura District, Sri Lanka. METHODS: S. aureus isolates were identified using mannitol salt agar, coagulase test and DNAase test. The agar plate dilution method was conducted to determine the minimum inhibitory concentration (MIC) of oxacillin against S. aureus. Antimicrobial susceptibility testing for other antibiotics was performed against MRSA isolates using antibiotic containing discs. To assess the MRSA transmission from livestock to humans, we have grouped MRSA strains according to antimicrobial susceptibility patterns against the tested antibiotics. RESULTS: Among MRSA isolates, 14 different groups with similar MIC and antibiotic susceptibility patterns were identified. Of those, 2 groups amongst pigs and pig farmers showed a significant relationship (p=0.031). The other groups did not show any significant relationship between animals and the farmers. The percentages of MRSA prevalence in pigs and pig farmers were 26.6% each, in poultry and poultry farmers 8.3% and 13.3% respectively, in cattle and cattle farmers 8.3% and 3%. Compared to human MRSA isolates, animal isolates were significantly more resistant to ciprofloxacin (p=0.031), gentamicin (p=0.010) and clindamycin (p=0.011). Similarly, animal methicillin susceptible Staphylococcus aureus (MSSA) isolates were significantly more resistant to ciprofloxacin (p=0.022) and doxycycline (p=0.012). CONCLUSION: Pig farming showed a higher prevalence and 2.4 times higher risk (OR=2.4, CI95%: 1.2-4.8) of likely transmission of MRSA between animals and humans than cattle and poultry farming. Overall, 65% of MRSA and MSSA animal isolates were multidrug resistant.

Review on Usage of Vancomycin in Livestock and Humans: Maintaining Its Efficacy, Prevention of Resistance and Alternative Therapy.

Vancomycin is one of the "last-line" classes of antibiotics used in the treatment of life-threatening infections caused by Gram-positive bacteria. Even though vancomycin was discovered in the 1950s, it was widely used after the 1980s for the treatment of infections caused by methicillin-resistant Staphylococci, as the prevalence of these strains were increased. However, it is currently evident that vancomycin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci have developed for various reasons, including the use of avaparcin-an analog of vancomycin-as a feed additive in livestock. Therefore, prophylactic and empiric use of antibiotics and their analogues need to be minimized. Herein we discuss the rational use of vancomycin in treating humans, horses, farm animals, and pet animals such as dogs, cats, and rabbits. In present day context, more attention should be paid to the prevention of the emergence of resistance to antibiotics in order to maintain their efficacy. In order to prevent emergence of resistance, proper guidance for the responsible use of antimicrobials is indispensable. Therefore, almost all stakeholders who use antibiotics should have an in-depth understanding of the antibiotic that they use. As such, it is imperative to be aware of the important aspects of vancomycin. In the present review, efforts have been made to discuss the pharmacokinetics and pharmacodynamics, indications, emergence of resistance, control of resistance, adverse effects, and alternative therapy for vancomycin.

Spondylodiscitis Caused by Enterobacter agglomerans.

All over the globe, the incidence of vertebral infection is rising. Nowadays, compared to tuberculous variety, pyogenic spondylodiscitis incidence is high. The increase in the susceptible population and improved diagnostics summatively contributed to this. In clinical grounds, differentiation of pyogenic and tuberculous spondylodiscitis is well defined. Enterobacter agglomerans is a hospital contaminant and associated with infections in immunocompromised individuals and intravenous lines. It causes a wide array of infections. Enterobacter agglomerans spondylodiscitis is unusual and there are, around the globe, only less than 31 suspected cases that have been previously reported. Enterobacter agglomerans histology mimics tuberculous rather than pyogenic spondylodiscitis. A 65-year-old farming lady, while being in hospital, developed sudden onset spastic paraparesis with hyperreflexia. Later blood culture revealed Enterobacter agglomerans with 41-hour incubation in 99.9% probability from Ramel identification system. Her initial ESR was 120 mm/first hour. Isolate was susceptible to ciprofloxacin and intravenous followed with oral therapy shows a drastic ESR fall and improved clinical response. Differentiation of tuberculous and pyogenic spondylodiscitis is very much important in management point of view. Therefore, blood culture has a role in diagnosis of spondylodiscitis. ESR can be used as important inflammatory marker in monitoring the response to treatment. Retrospectively, ESR would aid in reaching a definitive diagnosis.

Detection of alkaptonuria in a 1-week-old infant.

Alkaptonuria is a rare disorder that results from an inherited deficiency of aromatic amino acid metabolism. Only 21% of the children under the age of 1 year having the disease are identified in clinics. We report a case of a 1-week-old child of a first-degree consanguineous couple with a symptom of frequent nappy staining. Analysis of urine showed a homogentisic acid concentration exceeding 200 mg/dL. The physical examination revealed that the child was healthy. The parents' watchfulness and the close attention paid to the child were the keys to the early detection of this rare disease. After identifying the disease, adequate follow-up of the patient is important to reduce further complications. Anti-inflammatory therapy and increasing the muscle strength by exercises such as swimming would be useful to restrict joint pains and immobilisation. A low protein diet also could be recommended; that fact is yet to be proven by clinical trials.