Economic and Diagnostic Biomarker Tests of Neonatal Sepsis: A Prospective Study from a Tertiary Care Hospital in a Low-Income Country.

Background: Neonatal sepsis is a leading cause of morbidity and mortality in low-and middle-income countries (LMICs). There are several sophisticated biomarkers; however, they are still insufficient in precision. In this perspective, our study aims to search for a pragmatic diagnostic biomarker in the age category. Methods: A cross-sectional study was conducted over six months(April-September 2018). All neonates with a diagnosis of probable sepsis were included. Logistic regression analysis of demographic variables was done to elucidate any association with confirmed sepsis cases. The median with interquartile range (IQR)] and mean with standard deviation (SD) were calculated, and then compared. The area under the receiver operating characteristic curve (AUROC) of the commonly opted biomarker tests [distribution width of red blood cells (RDW) and platelets(PDW), mean platelet volume(MPV), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)] was compared to the culture-confirmed case. Results: Of the 171 suspected sepsis subjects, we discovered a significant burden of newborn sepsis, with 18.7% of cases being culture-confirmed. 66 Early-onset sepsis(EOS) and 105 Late-onset sepsis(LOS) probable sepsis cases were enrolled. A higher incidence was revealed among male infants 24(14%) compared to females 8(4.7%). On logistic regression analysis, preterm birth [odds ratio (OR): 10.9, 95% confidence interval (CI): 4.5-26.9] and low birth weight (OR: 6.5, 95% CI: 2.4-17.9) were significantly associated. Coagulase-negative Staphylococcus aureus (CoNS) (n =6) among gram-positive, and Pseudomonas aeruginosa (n =6) was among gram-negative, were the leading etiologies. Escherichia coli (n =3) was the predominant bacteria in EOS subjects, while Pseudomonas aeruginosa (n =6) among LOS. Median interquartile range(IQR): platelet count 144.5(99-192), red cell distribution width 18(16.9-20), CRP 6(3-18.3); and mean ± SD: MPV (11.7 ± 1.7); PDW (15.2 ± 3.5) were attained, among confirmed cases. The AUROC, of biomarker tests was attained in the order: PDW(0.86) > MPV(0.81) > RDW(0.76) > CRP(0.67) > ESR(0.59); similarly, the cut-off order was >11.2, >10.4, >16.8, >2.9, >4.5, respectively. Conclusions: Our finding shows an increment in the width and volume of RBCand platelet: RDW, MPV, and PDW have a diagnostic role in neonatal sepsis.

Neglected Case of Human Balantidiasis: Presumed as Antibiotic-Associated Diarrhoea.

Background: Balantidiasis, due to its rare human incidence and nonspecific clinical presentations often neglected from the diagnosis considerations; however, a potent pathogen. Herein, we report a case of neglected balantidiasis presumed as antibiotic-associated diarrhoea. Case Presentation. A 27-year-old policeman presented in Sindhuli Hospital, with a chief complaint of epigastric pain, nausea, decreased appetite for several days, and loose stools (3-4 episodes per day). Previously, he was under antibiotic therapy (amoxycillin) for tonsillitis. The health post clinician made a presumptive diagnosis as the side effects of the antibiotics; however, the symptoms were not resolved. Complete blood cell count (CBC) was normal; renal function test (RFT) and liver function (LFT) were within the normal ranges. Ultrasonography of the abdomen and ECG (electrocardiogram) showed normal findings. However, on routine stool actively motile trophozoites of Balantidium coli (B. coli) were seen. He was treated successfully with metronidazole 750 mg tabs orally three times daily for 5 days. Conclusion: Protozoal infections, like balantidiasis, might be excluded from the diagnostic consideration in antibiotic-associated diarrhoea cases. Therefore, meticulous review of nonspecific clinical presentation and validation of an etiology with support of diagnostic tests are mandatory.

Susceptibility pattern of Salmonella enterica against commonly prescribed antibiotics, to febrile-pediatric cases, in low-income countries.

BACKGROUND: In most low-income countries, febrile-pediatric-cases are often treated empirically with accessible antibiotics without periodic epidemiological surveillance, susceptibility testing, or minimal lethal dose calculations. With this backdrop, the study was undertaken to evaluate the susceptibility trend of Salmonella enterica against the commonly prescribed antibiotics. METHODS: All isolates of Salmonella enterica were identified by standard protocols of biotyping and serotyping, then tested against antibiotics by the modified Kirby disk-diffusion method. Minimum Inhibitory Concentration (MIC) of isolates was determined by the agar-dilution method and compared with disk diffusion results and on nalidixic-acid sensitive/resistant strains. RESULTS: Among 1815 febrile-pediatric patients, 90(4.9%) isolates of Salmonella enterica [serovar: Salmonella Typhi 62(68.8%) and Salmonella Paratyphi A 28(31.1%)] were recovered. The incidence of infection was higher among males, age groups 5 to 9, and patients enrolling in the out-patient department (OPD). On the disk-diffusion test, most isolates were sensitive against first-line drugs i.e.cephalosporins, and macrolides. However, against quinolones, a huge percentile 93.3%, of isolates were resistant [including 58 Typhiand 26 Paratyphiserovar] while nearly 14% were resistant against fluoroquinolones. When MICs breakpoint were adjusted as follows: 4 µg/ml for azithromycin, ≥1 µg/ml for ciprofloxacin, 2 µg/ml for ofloxacin, 8 µg/ml for nalidixic acid, and 1 µg/ml for cefixime, higher sensitivity and specificity achieved. Compared to other tested antibiotics, a low rate of azithromycin resistance was observed. Nevertheless, higher resistance against fluoroquinolones was observed on NARS strain. CONCLUSION: Higher susceptibility of Salmonella enterica to the conventional anti-typhoidal drugs (amoxicillin, chloramphenicol, cotrimoxazole, cephotaxime) advocates for its reconsideration. Although, the lower susceptibility against fluoroquinolones among nalidixic-acid-resistant Salmonella (NARS) strain negates its empirical use among the study age group.

Enhanced quantitative urine culture technique, a slight modification, in detecting under-diagnosed pediatric urinary tract infection.

OBJECTIVES: The pediatric urinary tract infection (UTI) often remains under-diagnosed or neglected owing to non-specific clinical presentations, patients failing to describe the actual situation and of clinical practice in diagnosis. The study was aimed to determine the etiologies of UTI in children with enhanced quantitative urine culture (EQUC) technique. RESULTS: Of enrolled 570 pediatric urine samples, the significant growth positivity was higher in EQUC 92 (16.15%) compared to standard urine culture (SUC) 73 (12.80%) technique. 20.6% of the significant isolates as detected with EQUC were missed on the SUC technique. The age group, in range 1-4 years, was more prone to the infection, where E. coli was the commonest pathogen. EQUC detected, probably all isolates, contributing UTI i.e. multidrug-resistant (MDR), extensive drug-resistant (XDR), and extended-spectrum ß-lactamase (ESBL) producers, as some of them skipped on the SUC technique. Of total organisms isolated from EQUC, 46% were ESBL producer, 56.5% were MDR, and 1.4% were XDR. However, 40.5% ESBL, 44% MDR but no XDR detected on SUC. Hence a simple modification on conventional culture protocol could be a crucial modification for the detection of etiologies, contributing UTI, and hence to reduce inapt antimicrobial burden.

Primary cutaneous actinomycosis: a diagnosis consideration in people living with HIV/AIDS.

BACKGROUND: Owing to similar clinical presentations, as of cutaneous disease of different etiologies, and extreme rarity in the global incidence; primary cutaneous actinomycosis often remains as diagnostic challenges. CASE PRESENTATION: Herein, we describe a case of primary cutaneous actinomycosis, erroneously treated as cutaneous tuberculosis, in a patient living with AIDS. On clinical examination, the characteristic lesion, resembling cutaneous tuberculosis, observed on the dorsum of a left leg. No other lesion elsewhere on the body was observed, however. Cytological examinations of the stabbed biopsy were negative for malignant cells; although hyper-keratosis and mild-acanthosis of epidermis, acute inflammatory infiltrates comprising plasma cell, macrophages and neutrophils were observed in the upper and mid dermis. The pus aspirated from lesion grew a molar tooth, adherent colonies in microaerophilic condition. Further, identifications and susceptibility pattern against recommended antibiotics were assessed as per the CLSI (Clinical and Laboratory Standard Institute) guidelines. Subsequently, the case was then, diagnosed as primary cutaneous actinomycosis. Radiographic imaging of abdomen and lungs were normal; no feature of disseminated actinomycosis seen. Penicillin G followed by Penicillin V, was prescribed for 12 months. The patient underwent progressive changes and no relapse noted on periodic follow-up. CONCLUSION: The case underscores cutaneous actinomycosis requires a diagnosis consideration, especially in People Living with HIV/AIDS (PLHA), where myriad of opportunistic cutaneous infections are common.

Diagnosis of tuberculosis from smear-negative presumptive TB cases using Xpert MTB/Rif assay: a cross-sectional study from Nepal.

BACKGROUND: In most developing countries, smear-negative pulmonary TB (SNPT) often gets missed from the diagnosis of consideration, though it accounts 30-65% of total PTB cases, due to deficient or inaccessible molecular diagnostic modalities. METHODS: The cross-sectional study enrolled 360 patients with clinical-radiological suspicion of SNPT in Tribhuvan University Teaching Hospital (TUTH). The patient selection was done as per the algorithm of Nepal's National Tuberculosis Program (NTP) for Xpert MTB/RIF testing. Participants' demographic and clinical information were collected using a pre-tested questionnaire. The specimens were collected, processed directly for Xpert MTB/RIF test according to the manufacturer's protocol. The same samples were stained using the Ziehl-Neelsen technique then observed microscopically. Both findings were interpreted; rifampicin-resistant, if obtained, on Xpert testing was confirmed with a Line Probe Assay. RESULT: Of 360 smear-negative sputum samples analyzed, 85(23.61%) found positive while 3(0.8%) of them were rifampicin resistance. The infection was higher in males, i.e. 60(25.3%) compared to female 25(20.3%). The age group, > 45(nearly 33%) with median age 42 ± 21.5, were prone to the infection. During the study period, 4.6% (515/11048) sputum samples were reported as smear-positive in TUTH. Consequently, with Xpert MTB/RIF assay, the additional case 16.5% (n = 85/515) from smear-negative presumptive TB cases were detected. Among the most occurring clinical presentations, cough and chest pain were positively associated with SNPT. While upper lobe infiltrates (36.4%) and pleural effusion (40.4%) were the most peculiar radiological impression noted in PTB patient. 94 multi-drug resistant(MDR) suspected cases were enrolled; of total suspects, 29(30.8%) samples were rifampicin sensitive, 1(1.06%) indeterminate, 3(3.19%) rifampicin-resistant while remaining of them were negative. 2(2.2%) MDR cases were recovered from the patient with a previous history of ATT, of total 89 previously treated cases enrolled However, a single rifampicin-resistant from the new suspects. CONCLUSION: With an application of the assay, the additional cases, missed with smear microscopy, could be sought and exact incidence of the diseases could be revealed.

Fatal strongyloidiasis after corticosteroid therapy for presumed chronic obstructive pulmonary disease.

INTRODUCTION: Strongyloidiasis is a neglected tropical disease with global prevalence. Under some cases of immune suppression (especially with corticosteroid administration), the nematode involved disseminates, leading to an amplified, possibly lethal hyper-infection syndrome. CASE PRESENTATION: A 56-year-old Nepalese man presenting with chief complaints of nausea, vomiting, joint pain and abdominal cramps was admitted to Sumeru Hospital. His past history revealed: chronic obstructive pulmonary disease (COPD), systemic hypertension and previously treated pulmonary tuberculosis. The patient had been treated with oral prednisolone (60 mg gl-1) for 8 days due to a presumed exacerbation of his COPD. Sequentially, he developed haemoptysis, chest tightness, frequent wheezing and worsening cough. Bronchoscopy showed severe diffuse alveolar haemorrhage; microbiological examination of broncho-alveolar lavage (BAL) was recommended. Examination of an acid fast bacilli stain preparation of BAL revealed filariform larvae of Strongyloides. Stool specimen examination revealed larvae of Strongyloides. The physical condition of the patient began to deteriorate; a few days after admission, vancomycin-sensitive Enterococcus faecium was isolated from a blood sample. He was treated with ivermectin and albendazole for strongyloides and linezolid plus vancomycin for E. faecium. However, the patient failed to recover from the illness and died. CONCLUSION: The findings of our study suggest that corticosteroid administration in strongyloidiasis can lead to the development of fatal strongyloides hyper-infection syndrome. Hence our experience suggests the need for early diagnosis of strongyloidiasis to avoid such an outcome. A deterioration of the patient's condition after the initiation of corticosteroid therapy in endemic areas should raise the possibility of strongyloidiasis.

A comparison of techniques to address the frequency of Helicobacter pylori positive dyspeptic patient.

OBJECTIVES: The study was aimed to compare the diagnostic techniques, for the detection of Helicobacter pylori infection, available in low-income countries, where molecular testing is not available or inaccessible to anyone. RESULTS: Of total enrolled patient, with the mean age of 41.4 ± 13.33 years, 24 (14 female; 10 male) were diagnosed to have been infected. The diagnosis was established based upon the gold standard test [either two of three tests: Rapid Urease Test (RUT), culture and histological examinations]. Of clinical presentation, the epigastric pain (75%) was the commonest; nevertheless, the endoscopic findings had shown an equivocal specificity since the larger percentile (58.3%) reported as normal findings, in a presumed dyspepsia. Based on the premise-with calculated sensitivity, specificity, and predictive values; the accuracy order observed as histology > RUT > serology > stool antigen test, in H. pylori detection from the clinical samples. The accuracy order of the diagnostic test may vary depending upon the laboratory settings and study population. Therefore, in reference to low-income countries, the clinicians must resort any available positive test so that the supporting positive rudiments would be an ancillary in augmenting the diagnostic accuracy.

Primary cutaneous nocardiosis: a diagnosis of consideration in a renal transplant recipient.

BACKGROUND: The cutaneous nocardiosis remains a diagnostic challenge: similar clinical presentations as of cutaneous diseases with different etiology-and the inherent difficulty in cultivating the pathogen. CASE PRESENTATION: Herein, we describe a case of primary cutaneous nocardiosis in a renal transplant recipient; treated with anti-tubercular drugs due to misdiagnosis of cutaneous tuberculosis. On clinical examinations, a few red erythematous papules with erosions and crusting seen, over prior surgery scar of renal transplant. Multiple basophilic colonies surrounded by neutrophilic abscesses and granulation tissue were seen on histopathological examinations. The presumptive identification was done by Ziehl-neelson staining, bacterial culture, biochemical interpretations, and susceptibility pattern of the isolates to antibiotics. Radiographic imaging of brain and lungs were normal; no feature of disseminated nocardiosis seen. After 3 months of an anti-microbial therapy i.e. TMP-SMX(sulfamethoxazole and trimethoprim); the patient underwent progressive changes no relapse noted; transplant function observed in a good state, found asymptomatic with limited side effects on a regular follow up till now. CONCLUSION: Cutaneous nocardiosis can occur in the renal-transplant patient. Therefore, a high degree of clinical suspicions, extensive clinical differentiation, early detection of the pathogen, apt selection of the antimicrobial therapy, correct dosing, and treatment duration is crucial for successful outcomes.

Catheter-Associated Urinary Tract Infection and Obstinate Biofilm Producers.

BACKGROUND: Biofilms, or colonies of uropathogen growing on the surface of indwelling medical devices, can inflict obstinate or recurring infection, thought-provoking antimicrobial therapy. METHODS: This prospective analysis included 105 urine samples from catheterized patients receiving intensive care. Ensuing phenotypic identification, antibiotic sensitivity test was performed by modified Kirby-Bauer disc diffusion method following CLSI guidelines; MDR isolates were identified according to the combined guidelines of the European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC). Biofilm-forming uropathogens were detected by the tissue culture plate (TCA) method. RESULTS: The predominant uropathogen in catheter-associated UTIs (CAUTIs) was Escherichia coli 57%, followed by Klebsiella pneumonia 15%, Pseudomonas aeruginosa 12%, Staphylococcus aureus 8%, Enterobacter spp. 3%, Enterococcus faecalis, Acinetobacter spp., and Proteus mirabilis 1.5%, of which 46% isolates were biofilm producers. Prime biofilm producers were Escherichia coli 33%, followed by Klebsiella pneumoniae 30%, Pseudomonas aeruginosa 20%, Staphylococcus aureus 10%, Acinetobacter, and Enterobacter 3.33%. Multidrug resistance associated with biofilm producers were greater than biofilm nonproducers. The Gram-negative biofilm producers found 96.15%, 80.76%, 73.07%, 53.84%, 53.84%, 46.15%, 19.23%, and 11.5% resistant to amoxyclave, ceftazidime, tetracycline, gentamicin, meropenem, nitrofurantoin, amikacin, imipenem, and fosfomycin, respectively. Gram-positive biofilm producers, however, were found 100% resistant to tetracycline, cloxacillin, and amoxyclave: 66.67% resistant to ampicillin while 33.33% resistant to gentamicin, ciprofloxacin, and nitrofurantoin. CONCLUSION: High antimicrobial resistance was observed in biofilm producers than non-biofilm producers. Of recommended antimicrobial therapies for CAUTIs, ampicillin and amoxicillin-clavulanate were the least active antibiotics, whereas piperacillin/tazobactam and imipenem were found as the most effectual for gram-negative biofilm producer. Likewise, amoxicillin-clavulanate and tetracycline were the least active antibiotics, whereas vancomycin, fosfomycin, piperacillin-tazobactam, and meropenem were found as the most effective antibiotic for Gram-positive biofilm producer. In the limelight, the activity fosfomycin was commendable against both Gram-positive and Gram-negative biofilm producers.

Cutaneous Tuberculosis: Clinicopathologic Arrays and Diagnostic Challenges.

The clinicopathological manifestations of cutaneous tuberculosis are diverse. The precise diagnosis is often overlooked, due to clinical presentations as those of cutaneous diseases with different etiology and the relative paucity of the pathogens in the lesions. Meanwhile, almost all of the diagnostic methods confer lower sensitivity and specificities which augments further diagnostic challenges. This article revises the current scenario of the disease's physiopathology and underscores clinicopathological challenges, due to multifaceted presentations of cutaneous tuberculosis, in the diagnosis.

Correction to: Pulmonary nocardiosis masquerading renascence of tuberculosis in an immunocompetent host: a case report from Nepal.

Following publication of the original article [1], a typesetting mistake is reported. The captions of Figure 2 and Figure 3 were interchanged. The incorrect and correct combination of the figures and captions are given in this Correction and the original article has been updated.

Pulmonary nocardiosis masquerading renascence of tuberculosis in an immunocompetent host: a case report from Nepal.

BACKGROUND: Pulmonary nocardiosis is an opportunistic infection in an immunocompromised patient; however, often neglected in the immunocompetent patient from the diagnosis considerations. CASE PRESENTATIONS: We describe a case of pulmonary nocardiosis masquerading renascence of tuberculosis, in a 51-years-Nepali farmer. After a 6 month of presumed successful antitubercular therapy; the patient develops the clinical presentations and radiological features showing similarities with that of tuberculosis and malignancy. MTB complex was not detected with Xpert MTB/RIF assay and cytological examinations were negative for the malignant cells, however. The Ziehl-Neelsen staining of the broncho-alveolar-lavage revealed acid-fast, thin branching filamentous organisms suggestive Nocardia spp. Further, identifications and susceptibility pattern against recommended antibiotics were assessed as per the CLSI guidelines. The case was then, subsequently, diagnosed as pulmonary nocardiosis. Trimethoprim-sulfamethoxazole was prescribed for 12 months. The patient underwent progressive changes and no relapse was noted in a periodic follow-up. CONCLUSIONS: This case underscores that pulmonary nocardiosis requires diagnostic considerations, regardless of a patient's immunologic status and other mimicking infections.

Disseminated Nocardiosis in renal transplant recipient under therapy for pulmonary tuberculosis: a case report.

BACKGROUND: Nocardiosis is an opportunistic infection in a patient with underlying immune suppression and organ transplant. Clinical syndromes are varied and ranges from pulmonary, disseminated, cutaneous along with central nervous system involvement. CASE PRESENTATION: Herein, we report a rare case of disseminated pulmonary nocardiosis with cerebral manifestation in a 66 year-old-Nepali farmer; with a history of renal transplantation and undergoing therapy for pulmonary tuberculosis. Radiographic imaging revealed multiple opacities of varying sizes in bilateral lung field mediastinal, retroperitoneal lymphadenopathy, and ill-defined lesion with surrounding edema seen in left occipitoparietal region of brain. Bacteriological assessments of bronchoalveolar lavage and purulent fluid extracted intra-operatively from the lesion confirmed the case as Nocardiosis. CONCLUSION: Disseminated Pulmonary nocardiosis with central nervous system involvement carries a poor prognosis. However, early diagnosis of the case, the administration of appropriate antibiotic, stereotactic aspiration alone or craniotomy has a successful outcomes even in a post renal transplant patient treated with anti tuberculosis treatment.