In Vitro Activity of Imipenem-Relebactam and Ceftolozane-Tazobactam against Resistant Gram-Negative Bacilli.

Understanding which antimicrobial agents are likely to be active against Gram-negative bacilli can guide selection of antimicrobials for empirical therapy as mechanistic rapid diagnostics are adopted. In this study, we determined the MICs of a novel ß-lactam-ß-lactamase inhibitor combination, imipenem-relebactam, along with ceftolozane-tazobactam, imipenem, ertapenem, meropenem, ceftriaxone, and cefepime, against 282 drug-resistant isolates of Gram-negative bacilli. For isolates harboring blaKPC (n = 110), the addition of relebactam to imipenem lowered the MIC50/MIC90 from 16/>128 µg/ml for imipenem alone to 0.25/1 µg/ml. For isolates harboring blaCTX-M (n = 48), the MIC50/MIC90 of ceftolozane-tazobactam were 0.5/16 µg/ml (83% susceptible). For isolates harboring blaCMY-2 (n = 17), the MIC50/MIC90 of ceftolozane-tazobactam were 4/8 µg/ml (47% susceptible). Imipenem-relebactam was active against most KPC-producing (but not NDM- or IMP-producing) Enterobacteriaceae and is an encouraging addition to the present antibiotic repertoire.

Differential Antimicrobial Susceptibilities of Granulicatella adiacens and Abiotrophia defectiva.

MICs of 25 Abiotrophia defectiva and 109 Granulicatella adiacens isolates were determined by broth microdilution. Using CLSI breakpoints, the susceptibilities of A. defectiva and G. adiacens isolates were, respectively, 24% and 34% to penicillin, 92% and 22% to ceftriaxone, 48% and 3% to cefepime, 72% and 87% to meropenem, 92% and 10% to cefotaxime, 100% and 97% to levofloxacin, 92% and 80% to clindamycin, and 24% and 50% to erythromycin. All isolates were susceptible to vancomycin. In the penicillin-susceptible subgroup, all A. defectiva isolates were susceptible to ceftriaxone; however, 62% of G. adiacens isolates were ceftriaxone nonsusceptible.

Characterization of plasmids in extensively drug-resistant acinetobacter strains isolated in India and Pakistan.

The blaNDM-1 gene is associated with extensive drug resistance in Gram-negative bacteria. This probably spread to Enterobacteriaceae from Acinetobacter spp., and we characterized plasmids associated with blaNDM-1 in Acinetobacter spp. to gain insight into their role in this dissemination. Four clinical NDM-1-producing Acinetobacter species strains from India and Pakistan were investigated. A plasmid harboring blaNDM-1, pNDM-40-1, was characterized by whole-genome sequencing of Acinetobacter bereziniae CHI-40-1 and comparison with related plasmids. The presence of similar plasmids in strains from Pakistan was sought by PCR and sequencing of amplicons. Conjugation frequency was tested and stability of pNDM-40-1 investigated by real-time PCR of isolates passaged with and without antimicrobial selection pressure. A. bereziniae and Acinetobacter haemolyticus strains contained plasmids similar to the pNDM-BJ01-like plasmids identified in Acinetobacter spp. in China. The backbone of pNDM-40-1 was almost identical to that of pNDM-BJ01-like plasmids, but the transposon harboring blaNDM-1, Tn125, contained two short deletions. Escherichia coli and Acinetobacter pittii transconjugants were readily obtained. Transconjugants retained pNDM-40-1 after a 14-day passage experiment, although stability was greater with meropenem selection. Fragments of pNDM-BJ01-like plasmid backbones are found near blaNDM-1 in some genetic contexts from Enterobacteriaceae, suggesting that cross-genus transfer has occurred. pNDM-BJ01-like plasmids have been described in isolates originating from a wide geographical region in southern Asia. In vitro data on plasmid transfer and stability suggest that these plasmids could have contributed to the spread of blaNDM-1 into Enterobacteriaceae.

Rates of caesarian section and trials and success of vaginal birth after caesarean sections in secondary care hospital.

We planned to investigate the rates of Caesarean Section (CS), potential Vaginal Births After previous Caesarean Section (VBAC), and successful VBAC in a secondary care hospital. We conducted an analytical retrospective study at Aga Khan Hospital for Women, Karimabad, Karachi, from October 2011 to September 2012. Data related to total deliveries, Lower Segment CS (LSCS), attempted VBAC and successful VBAC was retrieved from medical records. Total number of deliveries were 3266. Of these, 1021(31.26%) deliveries were conducted by CS. A total of 365(11.1%) had a previous history of one CS and VBAC trial was given to 33(9%) of these pregnancies. The success rate of VBAC was 21 (63.6%). Our results highlight that despite having limited resources, our rates of CS, VBAC trials and successful VBACs were within reasonable limits when compared with international rates.

Use of Corticosteroids in the management of Idiopathic Pulmonary Haemosiderosis: Do we have enough evidence.

Idiopathic Pulmonary Haemosiderosis (IPH) is a rare disease commonly affecting the paediatric population with approximately 500 globally reported cases in the literature. The disease usually presentswith a symptom triad consisting of ferropenic anaemia, cough with haemoptysis and diffuse bilateral alveolar infiltrates. Therapeutic options for this disorder are not only limited but also not fully effective. Moreover, corticosteroids remain the mainstay of IPH treatment. This communication reviews the available evidence in support of corticosteriod usage in the treatment of IPH. We conclude that the use of corticosteroid in IPH treatment is unfathomed and demands further investigation.

Inpatient satisfaction at tertiary care public hospitals of a metropolitan city of Pakistan.

OBJECTIVE: To determine the satisfaction of in-patients towards quality of service provision and environment of public-sector hospitals. METHODS: The cross-sectional study was conducted in four major public-sector hospitals of Karachi from December 2010 to February 2012. The questionnaire, besides the demographic details, also had 5-point Likert scale questions regarding satisfaction of patients with doctors, staff, administration and the hospital environment. SPSS 20 was used for statistical analysis and results were expressed as frequencies with percentages. RESULTS: Of the 710 subjects in the study, 475(67%) agreed that their doctors checked them with concentration and care. Staff was reported as being kind natured and well-mannered by 423(59.6%) and 451(63.5%) patients respectively. However, 414(58.3%) were not pleased with the sanitary condition of the hospital. Only 225(31.7%) got comfortable beds, while 498(70.14%) patients found bugs in beds. In terms of overall satisfaction 452(63.7%) were satisfied with the staff, 463(65.2%) with doctors, and 385(54.2%) with the hospital environment. CONCLUSION: Patients were relatively satisfied with the staff, but sanitary conditions and hospital environment were a concern for majority of the patients.

The right to live or die? A perspective on voluntary euthanasia.

"It is choice alone that is being honored, without regards for what is chosen." The debate on euthanasia in medical community stays unresolved. In this manuscript, we present arguments for and against euthanasia, review arguments from both the sides and conclude it with our opinion.

Clinical, microbiological and genomic characterization of Gram-negative bacteria with dual carbapenemases as identified by rapid molecular testing.

Objective: Dual carbapenemase-producing organisms (DCPOs) are an emerging threat that expands the spectrum of antimicrobial resistance. There is limited literature on the clinical and genetic epidemiology of DCPOs. Methods: DCPO isolates were identified by Xpert® Carba-R PCR testing of routine diagnostic cultures performed from 2018 to 2021 at a New York City health system. WGS was performed by Illumina and/or PacBio. Medical records of patients were reviewed for clinical and epidemiological data. Results: Twenty-six DCPO isolates were obtained from 13 patients. Klebsiella pneumoniae (n = 22) was most frequent, followed by Pseudomonas aeruginosa (n = 2), Escherichia coli (n = 1) and Enterobacter cloacae (n = 1). The most common DCPO combination was blaNDM/blaOXA-48-like (n = 16). Notably, 1.05% (24/2290) of carbapenem-resistant Enterobacterales isolates were identified as DCPOs. The susceptibility profiles matched the identified resistance genes, except for a K. pneumoniae (blaKPC/blaOXA-48-like) isolate that was phenotypically susceptible to meropenem. Eleven patients were hospitalized within the year prior to admission, and received antibiotic(s) 1 month prior. Seven patients were originally from outside the USA. Hypertension, kidney disease and diabetes were frequent comorbidities. Death in two cases was attributed to DCPO infection. WGS of eight isolates showed that carbapenemases were located on distinct plasmids, except for one K. pneumoniae isolate where NDM and KPC carbapenemases were located on a single IncC-type plasmid backbone. Conclusions: Here we characterized a series of DCPOs from New York City. Foreign travel, prior hospitalization, antibiotic usage and comorbidities were common among DCPO cases. All carbapenemases were encoded on plasmids, which may facilitate horizontal transfer.

Incidence and outcome of small for gestational age foetuses: an experience from a secondary care hospital.

The objective of the study was to determine the frequency and outcome of Small for Gestational Age (SGA) foetuses, and its association with the mode of delivery, foetal birthweight, maternal age and gestational age. It was a hospital-based descriptive study, conducted at Aga Khan Hospital for Women, Karachi, from January 2009 to December 2010. Mode of deliveries, foetal birthweight, maternal age and gestational age of SGA foetuses were recorded and analszed. Of a total of 6024 deliveries during the study period, 722 (11.98%) had SGA foetuses. Maternal age in such cased ranged between 20-40 years in 588 (81.44%), while 406 (56.23%) of these deliveries were in between 34-37 weeks of gestation. Besides, 396 (54.84%) cases were delivered vaginally. The incidence of SGA increased from 2009 to 2010 (13.13% vs 10.76%). The frequency of SGA foetuses tends to be significantly higher in Pakistan compared to the Western world. Prenatal care and better management can potentially avoid the occurrence of SGA deliveries, perinatal morbidity and mortality.

Oesophageal duplication cyst presenting as haemoptysis.

Duplications of the alimentary tract include a variety of cysts, diverticula, and tubular malformations, all believed to have embryological origin. The cysts are most commonly found in children, and the diagnosis is made in infancy in the majority of patients. We report a case of a two-and-a-half year old child, presenting with the history of repeated episodes of haematemesis. Upper GI endoscopy was unremarkable and the chest x-ray showed no pathology. Computed tomography (CT) angiogram revealed soft tissue density lesion in the right chest at the level of T6. Right thoracotomy suggested a cystic mass close to the oesophagus which was shown on histopathology to be lined with gastric mucosa consistent with oesophageal duplication cyst. To the best of our knowledge, this is the first case of its kind reported from Pakistan.

Meckel Gruber Syndrome: Second trimester diagnosis of a case in a non-consanguineous marriage.

Meckel-Gruber Syndrome (MKS) is a rare, autosomal recessive genetic disorder, incompatible with life. It is characterized by enlarged polycystic kidneys and post axial polydactyly. Foetal or neonatal death is caused by pulmonary hypoplasia. We report a case of a 35 year old woman who presented at 7 weeks of gestation of her sixth pregnancy. A transabdominal anomaly ultrasound performed for her current pregnancy at 18 weeks of gestation showed features consistent with MKS. The termination of pregnancy was declined and a live newborn female was delivered via an emergency caeserean section at 34 weeks of gestation due to previous history of lower segment caesarean section (LSCS) & leaking. Physical examination of the neonate confirmed the features of MKS. The neonate died within 4-5 hours of birth. This case represented a second trimester diagnosis of a recurrent case of MKS in a non-consanguineous marriage.

Current efficacy of antibiotics against Klebsiella isolates from urine samples - a multi-centric experience in Karachi.

Due to emergence of bacterial resistant strains, the effectiveness of current antibiotic treatment without culture/sensitivity testing is questionable. Our study aims to assess the present sensitivity profiles of Klebsiella isolates from urine samples and provide options for empiric prescription in critically ill patients. Klebsiella pneumoniae isolates collected over a period of 28 months till January 2011 from 1,617 urine samples of subjects presenting with Urinary Tract Infections were identified at a local diagnostic lab using standard protocol and subjected to Kirby-Bauer disk diffusion sensitivity testing. MICs were also estimated by E-nephelometry. Among 20 drugs used, low sensitivity was found to amoxicillin (0.1%), doxycycline (11.5%), nitrofurantoin (15.5%), amoxiclav (18.2%), gentamicin (35.4%), pipemidic acid, cephradine (40.3%) and cotrimoxazole (43.1%). The isolates were more sensitive to cefuroxime (55.9%), cefixime (57.7%), ciprofloxacin (62.5%), ofloxacin (63%), ceftriaxone (66.2%), ceftazidime (66.4%), cefotaxime (66.6%), fosfomycin (77.5%) and amikacin (89.4). Most effective were cefroperazone.sulbactam (95.8%), piperacillin.tazobactam (95.7%) and imipenem (97.7%). Self-medication, lack of awareness, and the misuse of antibiotics by doctors has exacerbated the menace of microbial resistance. The study warrants the prudent choice of drugs in adherence with prevailing sensitivity profiles.

Idiopathic pulmonary haemosiderosis presenting as severe iron deficiency anaemia--a case from Pakistan.

Idiopathic pulmonary haemosiderosis is an uncommon disorder, which is characterized by iron deficiency, recurrent haemoptysis and diffuse parenchymal infiltration on chest radiograph. We report an 8 year old child who had past history of multiple blood transfusions with diagnosis of iron deficiency anaemia and recurrent chest infection since the age of 21/2 year. At the age of 8 years, the child presented with fever and severe respiratory distress requiring intubation and ventilation. On Chest X-ray, bilateral white out was found and CT scan lung showed diffuse alveolar involvement. Lung biopsy confirmed haemosiderin-laden macrophages. Child was put on steroids and despite severe anaemia (Hb 3.2 g/dl), he showed improvement and survived. To our knowledge, this is the first case of idiopathic pulmonary haemosiderosis reported from Pakistan.

Assessment of research output at higher level of educaton in Pakistan.

OBJECTIVE: To evaluate the contribution towards research of medical universities and universities with affiliated medical colleges in Pakistan. METHODS: List of Pakistani medical universities and their published research annually from 2007 to 2010 was retrieved in April 2011 from the Higher Education Commission database with due permission. As per the Commission's criteria, only those publications were included that were indexed in Journal Citation Reports published by Thomson-Reuters. Publications were analysed for their year-wise, city-wise and university-wise distributions. Descriptive statistical analyses were performed by generating Box and Whisker plots. All illustrations were generated by using MS Office 2008 and/or Minitab for Macintosh. RESULTS: From 2007-2010, the total number of publications from all medical universities or universities with affiliated medical colleges in Pakistan was 5886. Of the total 26 such universities in Pakistan, only 20 had publications in 2007, 21 in 2008, 23 in 2009 and 24 in 2010. The total number of publications from all such universities in 2007, 2008, 2009 and 2010 was 875, 1504, 1563 and 1944 respectively. The highest number of publications (n=1447, 24.58%) was produced by the University of Karachi. With respect to city-wise distribution of publications, Karachi produced the highest number of papers, (n=3108, 52.86%). CONCLUSION: The number of research publications by Pakistani institutions imparting medical education is way below the international standards. The present study is the first of its kind, highlighting the significance of published medical research.

Correlation between Identification of ß-Lactamase Resistance Genes and Antimicrobial Susceptibility Profiles in Gram-Negative Bacteria: a Laboratory Data Analysis.

We reported the frequency of resistance gene detection in Gram-negative blood culture isolates and correlated these findings with corresponding antibiograms. Data were obtained from 1045 isolates tested on the GenMark Dx ePlex Blood Culture Identification Gram-Negative Panels at the Mount Sinai Hospital Clinical Microbiology Laboratory in New York from March 2019 to February 2021. Susceptibilities were performed using Vitek 2 (bioMérieux Clinical Diagnostics) or Microscan (Beckman Coulter Inc.). blaCTX-M was detected in 26.4% Klebsiella pneumoniae, 23.5% Escherichia coli, and 16.4% Proteus mirabilis isolates. As would be expected, both blaCTX-M and blaCTX-M negative isolates were likely to be susceptible to newer agents while blaCTX-M positive isolates were more likely to be resistant to earlier generations of beta-lactam antibiotics. 3/204 blaCTX-M-positive isolates were found to be ceftriaxone-susceptible. Conversely, 2.8% ceftriaxone nonsusceptible strains were negative for all ß-lactamase genes on the ePlex BCID-GN panel, including blaCTX-M. The prevalence of CTX-M-producing Enterobacterales remains high in the United States. A small number of blaCTX-M-positive isolates were susceptible to ceftriaxone, and a small number of ceftriaxone nonsusceptible isolates were negative for blaCTX-M. Further studies are needed to determine the optimal management when an isolate is phenotypically susceptible to ceftriaxone, but blaCTX-M is detected. IMPORTANCE There is limited literature on corresponding results obtained from rapid molecular diagnostics with the antibiotic susceptibility profile. We reported a correlation between the results obtained from ePlex and the antibiograms against a large collection of Gram-negative bacteria. We reported that there can be a discrepancy in a small number of cases, but the clinical significance of that is unknown.

Lemierre's syndrome associated with hypervirulent Klebsiella pneumoniae: A case report and genomic characterization of the isolate.

We describe a case of Lemierre's syndrome (LS) caused by a hypervirulent strain of Klebsiella pneumoniae in a 63-year-old female with hypertension, hyperlipidemia, and diabetes mellitus, who presented with right neck pain and fevers. Computerized tomography of the neck and chest revealed an occluded right internal jugular vein secondary to thrombosis and septic emboli in lungs. Blood cultures grew K. pneumoniae. The patient was treated with ampicillin-sulbactam and then transitioned to amoxicillin-clavulanate to complete a 6-week course of antibiotics, and a 3-month course of rivaroxaban. String test of the K. pneumoniae isolate was positive at 2 cm. Whole genome sequencing identified several genes associated with the hypervirulent strain, notably the genes encoding for aerobactin (iucA and iucB) and salmochelin (iroB) iron acquisition systems. LS can rarely be caused by K. pneumoniae. Clinicians should monitor for known complications, such as septic emboli in patients with LS.