Clinical presentation and outcome of enteric fever in adult patients with cancer: a perspective from Pakistan.

Introduction. Enteric fever is a significant health concern in endemic countries. While extensive research has been conducted to understand its presentation and outcomes in non-cancer patients, limited data exist on its impact on cancer patients. This descriptive study aims to investigate the clinical presentation and outcome in cancer patients. Methodology. This retrospective observational study analysed 90 adult cancer patients from a single centre in Pakistan from January 2017 to December 2022. Inclusion criteria involved documented blood culture infections with Salmonella typhi or paratyphi A, B, or C. We examined clinical presentation, laboratory parameters, antimicrobial resistance, complications, and outcomes. Additionally, we explored the effects of chemotherapy, comorbidities, type of malignancy, and patient age on complications and mortality. Results. Salmonella typhi was the most prevalent organism (72.2 %), followed by Salmonella paratyphi A (22.2 %) and B (5.5 %). Variably-resistant isolates constituted 51.5 %, multi-drug resistant (MDR) isolates accounted for 20 %, extensively drug-resistant (XDR) for 14.4 % and ESBL-producers for 15.5 %, of all enteric fever infections. Enteric fever-associated complications were observed in 21.1 % of cases. Chemotherapy in the preceding month did not affect mortality, nor did age, gender, or malignancy type. However, comorbidities were statistically significant for mortality (p-value 0.03). A total of 8.8 % of patients required ICU care, and the all-cause 30 day mortality rate was 13.3 % Conclusion. Enteric fever remains prevalent in our geographical region. Unlike non-typhoidal Salmonella (NTS), enteric fever does not behave differently in an immunocompromised population, including cancer patients.

Trends in typhoid fever during the COVID-19 pandemic in Pakistan.

INTRODUCTION: Pakistan has been experiencing an extensively drug-resistant (XDR) outbreak of typhoid for some years. We sought to evaluate how the COVID-19 pandemic impacted typhoid epidemiology in Pakistan, from the beginning of the pandemic in 2020 through the end of 2022, and the reduction of COVID-19 cases. METHODOLOGY: We compared national public COVID-19 data with retrospectively obtained patient data of confirmed S. Typhi isolates between January 2019 and December 2022 from Shaukat Khanum Memorial Cancer Hospital and Research Centre and the hospital's extended network of laboratory collection centers across Pakistan. RESULTS: We observed that during the early onset of the COVID-19 pandemic and COVID-19 peaks, typhoid positivity generally decreased. This suggests that restrictions and non-pharmaceutical interventions that limited social interactions and promoted good sanitation and hygiene practices had a positive secondary effect on typhoid. This led to an overall yearly decrease in typhoid positivity between 2019 to 2021. However, the percentage of S. Typhi cases isolated that were ceftriaxone-resistant continued to increase, suggesting the continued dominance of XDR typhoid in Pakistan. In 2022, with the alleviation of pandemic restrictions, we observed increased typhoid positivity and COVID-19 and typhoid positivity started to follow similar trends. CONCLUSIONS: Given the continued presence of COVID-19 along with XDR typhoid in Pakistan, it will be imperative to use differential testing to ensure that the epidemiology of each reported is accurate, the spread of each it contained, and that antibiotics are not misused. The use of approved vaccinations will lessen the burden of both diseases.

The yeast genus Tardiomyces gen. nov. with one new species and two new combinations.

PURPOSE: Rare yeasts species are increasingly reported as causative agents of invasive human infection. Proper identification and antifungal therapy are essential to manage these infections. Candida blankii is one of these emerging pathogens and is known for its reduced susceptibility to multiple antifungals. METHODS: To obtain more insight into the characteristics of this species, 26 isolates reported as C. blankii were investigated using genetic and phenotypical approaches. RESULTS: Among the 26 isolates, seven recovered either from blood, sputum, urine, or the oral cavity, displayed substantial genetic and some phenotypical differences compared to the other isolates, which were confirmed as C. blankii. We consider these seven strains to represent a novel species, Tardiomyces depauwii. Phylogenomics assigned C. blankii, C. digboiensis, and the novel species in a distinct branch within the order Dipodascales, for which the novel genus Tardiomyces is erected. The new combinations Tardiomyces blankii and Tardiomyces digboiensis are introduced. Differences with related, strictly environmental genera Sugiyamaella, Crinitomyces, and Diddensiella are enumerated. All three Tardiomyces species share the rare ability to grow up to 42 °C, display slower growth in nutrient-poor media, and show a reduced susceptibility to azoles and echinocandins. Characteristics of T. depauwii include high MIC values with voriconazole and a unique protein pattern. CONCLUSION: We propose the novel yeast species Tardiomyces depauwii and the transfer of C. blankii and C. digboiensis to the novel Tardiomyces genus.

Decoding the historical tale: COVID-19 impact on haematological malignancy patients-EPICOVIDEHA insights from 2020 to 2022.

Background: The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced. Methods: The EPICOVIDEHA registry (National Clinical Trials Identifier, NCT04733729) gathers COVID-19 data from hematological malignancy patients since the pandemic's start worldwide. It spans various global locations, allowing comprehensive analysis over the first three years (2020-2022). Findings: The EPICOVIDEHA registry collected data from January 2020 to December 2022, involving 8767 COVID-19 cases in hematological malignancy patients from 152 centers across 41 countries, with 42% being female. Over this period, there was a significant reduction in critical infections and an overall decrease in mortality from 29% to 4%. However, hospitalization, particularly in the ICU, remained associated with higher mortality rates. Factors contributing to increased mortality included age, multiple comorbidities, active malignancy at COVID-19 onset, pulmonary symptoms, and hospitalization. On the positive side, vaccination with one to two doses or three or more doses, as well as encountering COVID-19 in 2022, were associated with improved survival. Interpretation: Patients with hematological malignancies still face elevated risks, despite reductions in critical infections and overall mortality rates over time. Hospitalization, especially in ICUs, remains a significant concern. The study underscores the importance of vaccination and the timing of COVID-19 exposure in 2022 for enhanced survival in this patient group. Ongoing monitoring and targeted interventions are essential to support this vulnerable population, emphasizing the critical role of timely diagnosis and prompt treatment in preventing severe COVID-19 cases. Funding: Not applicable.

The mortality of COVID-19 in CML patients from 2020 until 2022: results from the EPICOVIDEHA survey.

Since the beginning of the COVID-19 pandemic, there has been an overall improvement in patient mortality. However, haematological malignancy patients continue to experience significant impacts from COVID-19, including high rates of hospitalization, intensive care unit (ICU) admissions, and mortality. In comparison to other haematological malignancy patients, individuals with chronic myeloid leukemia (CML) generally have better prognosis. This study, conducted using a large haematological malignancy patient database (EPICOVIDEHA), demonstrated that the majority of CML patients experienced mild infections. The decline in severe and critical infections over the years can largely be attributed to the widespread administration of vaccinations and the positive response they elicited. Notably, the mortality rate among CML patients was low and exhibited a downward trend in subsequent years. Importantly, our analysis provided confirmation of the effectiveness of vaccinations in CML patients.

Case of Carbapenem-Resistant Salmonella Typhi Infection, Pakistan, 2022.

Salmonella Typhi infection in a patient in Pakistan initially responded to standard treatment but failed to respond to subsequent treatment. The first strain was susceptible to carbapenems and azithromycin; subsequent strains harbored the NDM-5 gene. Treatment with a combination of intravenous meropenem and colistin was successful. Carbapenem-resistant Salmonella Typhi emergence will hinder treatment.

Pan Drug-Resistant Salmonella Serovar Typhi Septicaemia In A Child: A Case Report.

Typhoid fever, caused by Salmonella enterica serovar Typhi, is a common cause of febrile illness, especially in lower middle-income countries. The only known reservoirs of this infection are humans, and it is prevalent in areas with limited availability of clean drinking water and sanitary conditions. Lately, extensively drug-resistant Salmonella ser. Typhi (XDR S. Typhi) has emerged as one of Pakistan's most challenging public health concerns. Here, we report a case of relapsed typhoid fever in a child, in whom the isolate was found to be resistant to meropenem and azithromycin.

Prospective analysis of febrile neutropenia patients with bacteraemia: the results of an international ID-IRI study.

OBJECTIVES: Bacteraemia during the course of neutropenia is often fatal. We aimed to identify factors predicting mortality to have an insight into better clinical management. METHODS: The study has a prospective, observational design using pooled data from febrile neutropenia patients with bacteraemia in 41 centres in 16 countries. Polymicrobial bacteraemias were excluded. It was performed through the Infectious Diseases-International Research Initiative platform between 17 March 2021 and June 2021. Univariate analysis followed by a multivariate binary logistic regression model was used to determine independent predictors of 30-d in-hospital mortality (sensitivity, 81.2%; specificity, 65%). RESULTS: A total of 431 patients were enrolled, and 85 (19.7%) died. Haematological malignancies were detected in 361 (83.7%) patients. Escherichia coli (n = 117, 27.1%), Klebsiellae (n = 95, 22% %), Pseudomonadaceae (n = 63, 14.6%), Coagulase-negative Staphylococci (n = 57, 13.2%), Staphylococcus aureus (n = 30, 7%), and Enterococci (n = 21, 4.9%) were the common pathogens. Meropenem and piperacillin-tazobactam susceptibility, among the isolated pathogens, were only 66.1% and 53.6%, respectively. Pulse rate (odds ratio [OR], 1.018; 95% confidence interval [CI], 1.002-1.034), quick SOFA score (OR, 2.857; 95% CI, 2.120-3.851), inappropriate antimicrobial treatment (OR, 1.774; 95% CI, 1.011-3.851), Gram-negative bacteraemia (OR, 2.894; 95% CI, 1.437-5.825), bacteraemia of non-urinary origin (OR, 11.262; 95% CI, 1.368-92.720), and advancing age (OR, 1.017; 95% CI, 1.001-1.034) were independent predictors of mortality. Bacteraemia in our neutropenic patient population had distinctive characteristics. The severity of infection and the way to control it with appropriate antimicrobials, and local epidemiological data, came forward. CONCLUSIONS: Local antibiotic susceptibility profiles should be integrated into therapeutic recommendations, and infection control and prevention measures should be prioritised in this era of rapidly increasing antibiotic resistance.

Antibiotics Associated With Clostridium difficile Infection.

Introduction Clostridium difficile (C. difficile) is one of the major causes of diarrhea transmitted by the fecal-oral route. C. difficile type BI/NAP1/027 is responsible for the most severe C. difficile infection (CDI). It is a major cause of antibiotic-associated diarrhea followed by Clostridium perfringens, Staphylococcus aureus,and Klebsiella oxytoca. Historically, clindamycin, cephalosporins, penicillins, and fluoroquinolones were related to CDI. We conducted this study to evaluate the antibiotics associated with CDI in recent times. Methods We conducted a retrospective, single-center study over a period of eight years. A total of 58 patients were enrolled in the study. Patients with diarrhea and positive C. difficile toxin in stool were evaluated for antibiotics given, age, presence of malignancy, previous hospital stay for more than three days in the last three months, and any comorbidities. Results Among patients who developed CDI, prior antibiotics for at least four days duration were given in 93% (54/58) of patients. The most common antibiotics associated with C. difficile infection were piperacillin/tazobactam in 77.60% (45/58), meropenem in 27.60% (16/58), vancomycin in 20.70% (12/58), ciprofloxacin in 17.20% (10/58), ceftriaxone in 16% (9/58), and levofloxacin in 14% (8/58) of patients, respectively. Seven percent (7%) of patients with CDI did not receive any prior antibiotics. Solid organ malignancy was present in 67.20% and hematological malignancy in 27.60% of CDI patients. Ninety-eight percent (98%, 57/58) of patients treated with proton pump inhibitors, 93% of patients with a previous hospital stay for more than three days, 24% of patients with neutropenia, 20.1% of patients aged more than 65 years, 14% of patients with diabetes mellitus, and 12% of patients with chronic kidney disease also developed C. difficile infection. Conclusion The antibiotics associated with C. difficile infection are piperacillin/tazobactam, meropenem, vancomycin, ciprofloxacin, ceftriaxone, and levofloxacin. Other risk factors for CDI are proton pump inhibitor use, prior hospital admission, solid organ malignancy, neutropenia, diabetes mellitus (DM), and chronic kidney disease (CKD).

Reporting of Azithromycin Activity against Clinical Isolates of Extensively Drug-Resistant Salmonella enterica Serovar Typhi.

This study aimed to evaluate the minimum inhibitory concentration (MIC) of azithromycin (AZM) in clinical isolates of extensively drug-resistant (XDR) Salmonella Typhi (i.e., resistant to chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole, fluoroquinolones, and third-generation cephalosporin) using the E-test versus the broth microdilution method (BMD). From January to June 2021, a retrospective cross-sectional study was carried out in Lahore, Pakistan. Antimicrobial susceptibility was performed initially by the Kirby-Bauer disk diffusion method for 150 XDR Salmonella enterica serovar Typhi isolates, and MICs of all the recommended antibiotics were determined by the VITEK 2 (BioMérieux) fully automated system using Clinical Laboratory Standard Institute (CLSI) 2021 guidelines. The E-test method was used to determine AZM MICs. These MICs were compared with the BMD, which is the method recommended by the CLSI but not adopted in routine laboratory reporting. Of 150 isolates, 10 (6.6%) were resistant by disk diffusion. Eight (5.3%) of these had high MICs against AZM by the E-test. Only three isolates (2%) were resistant by E-test, having an MIC of 32 µg/mL. All eight isolates had a high MIC by BMD with different MIC distributions, but only one was resistant, having an MIC of 32 µg/mL by BMD. The sensitivity, specificity, negative predictive value, positive predictive value, and diagnostic accuracy of the E-test method versus BMD were 98.65%,100%, 99.3%, 33.3%, and 98.6%, respectively. Similarly, the concordance rate was 98.6%, negative percent agreement was 100%, and positive percent agreement was 33%. The BMD is the most reliable approach for reporting AZM sensitivity in XDR S. Typhi compared with the E-test and disk diffusion methods. Potentially, AZM resistance in XDR S. Typhi is around the corner. Sensitivity patterns should be reported with MIC values, and if possible, higher values should be screened for the presence of any potential resistance genes. Antibiotic stewardship should be strictly implemented.

Identification of Multiple Variant Extensively Drug-Resistant Typhoid Infections across Pakistan.

Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a life-threatening bacterial infection. Recently, an outbreak of a new sublineage of extensively drug resistant (XDR) S. Typhi emerged in Pakistan in the province of Sindh. This sublineage had both a composite multidrug resistance transposon integrated on the chromosome and an acquired IncY plasmid carrying the extended spectrum beta-lactamase, blaCTX-M-15, which conferred resistance to third-generation cephalosporins. We observed previously that XDR typhoid had spread beyond the originating southern Sindh Province. Thus, we sought to determine the genetic diversity of 58 ceftriaxone-resistant S. Typhi clinical isolates by whole genome sequencing collected across Pakistan from November 2018 to December 2020 to provide insights into the molecular epidemiology of the evolving outbreak. We identify multiple novel genomic integrations of the extended spectrum beta-lactamase gene into the chromosome in S. Typhi, revealing the existence of various XDR typhoid variants circulating in the country. Notably, the integration of the IncY plasmid bearing antibiotic resistance genes may allow for subsequent plasmid acquisition by these variants, potentially leading to further plasmid-borne multidrug resistance. Our results can inform containment initiatives, help track associated outcomes and international spread, and help determine how widespread the risk is.

Clinical Characteristics and Outcomes of Pneumocystis jirovecii Pneumonia in Cancer Patients From a Tertiary Care Hospital.

Objective To investigate the predisposing factors, disease course, potential complications, role of primary prophylaxis, and overall outcomes of Pneumocystis jirovecii pneumonia (PJP) in cancer patients. Methods The study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, Pakistan. We analyzed the medical records of cancer patients diagnosed with PJP from January 2018 to December 2022 and collected data about demographic characteristics, clinical presentation, predisposing factors, treatment, complications, and mortality rates. We used SPSS 20 (IBM Corp., Armonk, NY, USA) for data analysis. Results Out of 84 patients, 59.5% (n=50) were males and most of the patients belonged to the age group 41 to 65 years. Sixty-seven point nine percent (67.9%; n=57) of patients had underlying hematological malignancy, including three bone marrow transplant recipients while 32.2% (n=27) of patients had underlying solid organ malignancy. We also observed the use of corticosteroids, rituximab, and fludarabine as predisposing factors in 15% (n=13), 27% (n=23), and 3.7%(n=03) of patients, respectively. The most common symptoms were dyspnea (88%; n=74), followed by fever (69%; n=58) and cough (69%; n=58). The former one was more prevalent in hematological malignancy patients as compared to the solid organ tumor group (p-value 0.001). We noted respiratory failure (45.2%; n=38), ICU stay (52.38%; n=44), death (32%; n=27), and shock (10.7% n=9) as the most common PJP-related complications. Moreover, all these complications were more frequent in hematological malignancy patients. We also observed that only three patients developed PJP while on adequate primary prophylaxis for this condition. The overall all-cause one-month mortality was 32% (n=27). Conclusion Cancer patients, especially those with hematological malignancies presenting with symptoms suggestive of PJP, need careful evaluation and preemptive treatment as PJP-related mortality is higher in cancer patients. Early diagnosis and treatment in this population can be lifesaving. Moreover, all cancer patients should receive PJP prophylaxis when indicated.

Trends of Vancomycin-Resistant Enterococcus Infections in Cancer Patients.

Objective Vancomycin-resistant Enterococcus (VRE) is an important cause of infection in immunocompromised populations. In Pakistan, very limited data are available regarding Enterococcus infection and its outcomes. We conducted this study to evaluate the trends including risk factors, treatment options, and outcomes of infections due to vancomycin-resistant enterococci in cancer patients in Pakistan. Methods We conducted a retrospective observational study. We extracted data from medical records of our center over a period of seven years. All admitted cancer patients with any vancomycin-resistant Enterococcus positive culture were included. The following parameters were evaluated: age, gender, type of cancer, febrile neutropenia, prior antibiotics, admission, comorbidities, system-wise infections (including bacteremia, catheter-related infection, pneumonia, urinary tract infections, intra-abdominal infection, bone and joint infections, skin and skin structure infections), intensive care unit admission, and 30-day all-cause mortality. Frequencies of infections, mortality, and drug susceptibility were evaluated over the course of seven years. Results Risk factors for enterococcal infection included prior exposure of piperacillin/tazobactam (n=209, 86.7%), meropenem (n=132, 54.8%), vancomycin (n=126, 52.3%), metronidazole (n=67, 27.8%), prior admission for more than 48 hours (n=198, 82.2%), and comorbidities (n=76, 31.5%), with acute kidney injury being most common (n=72, 95%) followed by diabetes mellitus (n=70, 92.1%). Precursor B cell acute lymphoblastic leukemia (pre-B ALL) was the most common malignancy in which infection occurred (n=54, 38.3%). Among patients who developed infection, 46% (n=111) had febrile neutropenia. Enterococcus species caused infection in 61% (n=147) and Enterococcus faecium in 39% (n=94). Bacteremia occurred in 45.2% (n=109) patients followed by urinary tract and intra-abdominal infection; 45.6% (n=110) patients were admitted to ICU, and 30-day all-cause mortality was 44.8% (n=108). Linezolid sensitivity was 100%. The total number of enterococci infections decreased over seven years. Frequency of E. species infection, bacteremia, intra-abdominal, skin-related infections, and recurrent infection also decreased, but the frequency of E. facium infections, ICU admission, and 30-day all-cause mortality was increased. Conclusion VRE infections have become less frequent but more severe in recent years with increase in mortality. Prior use of antibiotics (including piperacillin/tazobactam, vancomycin, carbapenems, and metronidazole), diagnosis of hematological malignancy, febrile neutropenia, diabetes mellitus, and renal failure are the risk factors for VRE infection. Bacteremia was the most common infection with high mortality rate. All strains remain sensitive to linezolid. Patients with these risk factors should be worked up for VRE and can be treated with linezolid empirically.

Country data on AMR in Pakistan in the context of community-acquired respiratory tract infections: links between antibiotic susceptibility, local and international antibiotic prescribing guidelines, access to medicine and clinical outcome.

BACKGROUND: Antimicrobial resistance (AMR) is one of the biggest threats to global public health. Selection of resistant bacteria is driven by inappropriate use of antibiotics, amongst other factors. COVID-19 may have exacerbated AMR due to unnecessary antibiotic prescribing. Country-level knowledge is needed to understand options for action. OBJECTIVES: To review the current situation with respect to AMR in Pakistan and initiatives addressing it. Identifying areas where more information is required will provide a call to action to minimize any further rises in AMR and improve patient outcomes. METHODS: National AMR initiatives, antibiotic use and prescribing in Pakistan, and availability of susceptibility data, in particular for the key community-acquired respiratory tract infection (CA-RTI) pathogens (Streptococcus pneumoniae and Haemophilus influenzae) were identified. National and international antibiotic prescribing guidelines for specific CA-RTIs (community-acquired pneumonia, acute otitis media and acute bacterial rhinosinusitis) commonly used locally were also reviewed, plus local antibiotic availability. Insights from a local clinician and clinical microbiologist were sought to contextualize this information. CONCLUSIONS: Pakistan is active in developing initiatives to address AMR such as compiling a National Action Plan. However, antibiotic consumption is high and although there is legislation in place prohibiting over-the-counter purchase of antibiotics, this is still possible. Healthcare professionals use local and international antibiotic prescribing guidelines for CA-RTIs when managing patients. As highlighted by the clinical microbiologist's expert comments, surveillance of AMR in locally prevalent microorganisms is lacking. A more standardized inclusive approach in developing local guidelines, using up-to-date local surveillance data of isolates from community-acquired infections, could make management guideline use more locally relevant for clinicians. This would pave the way for a higher level of appropriate antibiotic prescribing and improved adherence. This would, in turn, potentially limit AMR development and improve clinical outcomes for patients.

Continued Outbreak of Ceftriaxone-Resistant Salmonella enterica Serotype Typhi across Pakistan and Assessment of Knowledge and Practices among Healthcare Workers.

Pakistan is experiencing the first known outbreak of extensively drug-resistant (XDR) Salmonella enterica serotype Typhi (resistant to third-generation cephalosporins). The outbreak originated in Hyderabad in 2016 and spread throughout the Sindh Province. Whereas focus has remained on Sindh, the burden of XDR typhoid in Punjab, the most populous province, and the rest of the country is understudied. Using laboratory data from Shaukat Khanum Memorial Cancer Hospital and Research Centre in Lahore (Punjab Province) and its network of more than 100 collection centers across the country, we determined the frequency of blood culture-confirmed XDR typhoid cases from 2017 to 2019. We observed an increase in XDR typhoid cases in Punjab, with the percent of ceftriaxone resistance among Salmonella Typhi cases increasing from no cases in 2017, to 30% in 2018, and to 50% in 2019, with children bearing the largest burden. We also observed spread of XDR typhoid to the two other provinces in Pakistan. To assess prevailing knowledge and practices on XDR typhoid, we surveyed 321 frontline healthcare workers. Survey results suggested that inappropriate diagnostic tests and antibiotic practices may lead to underdiagnosis of XDR typhoid cases, and potentially drive resistance development and spread. Of those surveyed, only 43.6% had heard of XDR typhoid. Currently, serological tests are more routinely used over blood culture tests even though blood culture is imperative for a definitive diagnosis of typhoid fever. We recommend stronger liaisons between healthcare providers and diagnostic laboratories, and increased promotion of typhoid vaccination among healthcare workers and the general population.

Trends, Associations, and Antimicrobial Resistance of Salmonella Typhi and Paratyphi in Pakistan.

Typhoid remains a major cause of morbidity and mortality in endemic countries. This review analyzed typhoid burden changes in Pakistan and its association with contextual factors. A retrospective cohort study on blood culture-positive typhoid and antibiotic resistance was conducted from three tertiary hospitals and contextual factor data obtained from primary household surveys. Salmonella Typhi/Paratyphi positivity rates were estimated and trend analysis was carried out using positive cases out of total number of blood cultures performed. Contextual factors' associations were determined through bivariate correlation analysis, using STATA (SataCorp, College Station, TX). We report a total of 17,387 S. Typhi-positive and 8,286 S. Paratyphi A and B-positive specimens from 798,137 blood cultures performed. The results suggest an overall decline in typhoid incidence as S. Typhi positivity rates declined from 6.42% in 1992 to 1.32% in 2015 and S. Paratyphi (A and B) from 1.29% to 0.39%. Subgroup analysis suggests higher S. Typhi prevalence in adults older than 18 years, whereas S. Paratyphi is greater in children aged 5-18 years. The relative contribution of S. Paratyphi to overall confirmed cases increased from 16.8% in 1992 to 23% in 2015. The analysis suggests high burden of fluoroquinolone resistance and multidrug-resistant S. Typhi strains. Statistically significant associations of water, sanitation indicators, and literacy rates were observed with typhoid positivity. Despite some progress, typhoid remains endemic and a strong political will is required for targeted typhoid control strategies. A multipronged approach of improving water, sanitation and hygiene in combination with large-scale immunization in endemic settings of Pakistan could help reduce burden and prevent epidemics.

Risk factors and clinical outcomes for vancomycin-resistant enterococcus bacteraemia in hospitalised cancer patients in Pakistan: A case-control study.

OBJECTIVE: To compare the risk factors and outcomes of vancomycin-resistant enterococcus with vancomycin-sensitive enterococcus bacteraemia among hospitalised cancer patients. METHODS: The retrospective, case-control study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised data of cancer patients whose blood culture grew either vancomycin-sensitive or vancomycin-resistant enterococcus from January 2012 to December 2014. Multivariable logistic regression analyses were used to determine the factors associated with the development of vancomycin-resistant enterococcus bacteraemia and 12-week mortality. Stata 11 was used for data analysis. RESULTS: Of the 138 cases, 111(80%) were selected, of which 46(41.44%) were of vancomycin-resistant and 65(58.55%) were of vancomycin-sensitive enterococcus. Length of hospital stay prior to bacteraemia (adjusted odds ratio 1.18; 95% confidence interval 1.08-1.28) and use of vancomycin 30 days before the onset of bacteraemia (adjusted odds ratio 9.4; 95% confidence interval 1.70-52.19) were significant risk factors for the development of vancomycin-resistant enterococcus bacteraemia. The overall 12-week mortality rate was 29(63%) for patients with vancomycin-resistant bacteraemia and 28(43.1%) for vancomycin-sensitive enterococcus bacteraemia patients. Risk factors for mortality included the presence of shock at the time of the onset of bacteraemia (adjusted odds ratio 32.91; 95% confidence interval 3.02-358.81). CONCLUSIONS: The length of hospital stay and prior exposure to vancomycin were significant risk factors for the occurrence of vancomycin-resistant enterococcus bacteraemia.

Bacteraemia caused by Escherichia coli in cancer patients at a specialist center in Pakistan.

OBJECTIVE: To analyse the antimicrobial susceptibility patterns of Escherichia coli bacteraemia among cancer patients, and to assess the risk factors and outcomes of multidrug-resistant Escherichia coli bacteraemia. METHODS: The retrospective study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, and comprised medical records of patients with Escherichia coli bacteraemia presenting between December 2012 and November 2013. Multivariable logistic regression analyses were used to determine the factors associated with the development and 30-day mortality of multidrug-resistant Escherichia coli bacteraemia. RESULTS: Out of 1603 episodes of bacteraemia, 227(35.6%) were caused by E.coli, of which 98(43.2%) were multidrug-resistant. In multivariable analysis, age less than 18 years (adjusted odds ratio 3.92; 95% confidence interval 1.43-10.68), presence of central venous catheter (adjusted odds ratio 2.12; 95% confidence interval 1.04-4.33) and exposure to piperacillin/tazobactam within 90 days prior to infection (adjusted odds ratio 2.37; 95% confidence interval 1.15-4.86) were identified as independent risk factors for acquisition of multidrug-resistant Escherichia coli bacteraemia. The overall 30 day mortality rate was 35.2% (80/227). Risk factors for mortality were intensive care unit admission (adjusted odds ratio 3.95; 95% confidence interval 1.79-8.71) and profound neutropenia (adjusted odds ratio 4.03; 95% confidence interval 1.55-10.49). CONCLUSIONS: Bloodstream infections with multidrug-resistant Escherichia coli were common in cancer patients. However it was not a predictor of mortality.

Evaluation of predominant Neisseria gonorrhoeae strain types and its correlation with fluoroquinolone resistance in Pakistan.

OBJECTIVE: To study the predominant Neisseria gonorrhoeae strain types in Pakistan and to evaluate their correlation with fluoroquinolone resistance. METHOD: A total of 314 strains were collected from 2007-2009. Of these 112 strains were randomly selected for serotyping via the coagglutination technique. Fluoroquinolone susceptibility was checked through the E-test method. Chi square was performed to assess the correlation between the strain type and fluoroquinolone resistance pattern. RESULTS: N. gonorrhoeae isolates were typed in two serogroups and 28 serovars. Serogroup WI comprised 40% (n = 45) whereas WII/WIII was 60% (n = 67). Most commonly isolated serovar belonged to serogroup WI namely Aorst (10%). The other predominant circulating serovars of the serogroup WI were Aost (9%) and Ast (8%) and Bsy (8%), Bopyt (5%) and Bprt (4.5%) in the serogroup WII/III. Fluoroquinolone resistance was 98%, with an MIC of 2 microg/mL in 47%, 4 microg/mL in 36% and > 32 microg/mL in 12% of the isolates. On inferential analysis no significant correlation was observed between fluoroquinolone resistance and any particular serovars. CONCLUSION: A diverse population of N. gonorrhoeae serovars suggesting influx of a variety of gonococcal strains with high fluoroquinolone resistance was identified. This resistance was not associated with any particular serovars, so we speculated inappropriate use of fluoroquinolones in the community to be a major cause. Injudicious fluoroquinolone use in the community should be strongly discouraged to curtail increase in antimicrobial resistance. Furthermore, continuous surveillance of prevalent serovars will be critical to assess genetic alterations of endemic and imported strains to design effective disease control measures.

Evaluation of prevalence of low and high level mupirocin resistance in methicillin resistant Staphylococcus aureus isolates at a tertiary care hospital.

OBJECTIVE: To evaluate the trend of mupirocin resistance in MRSA, isolated at the Clinical Microbiology Laboratory of a tertiary care hospital. METHODS: A total of 200 MRSA strains recovered over a 2 year period from various body sites were tested using the 5 and 200 microg discs of mupirocin to detect its resistance. RESULTS: High level and low level mupirocin resistance were detected in zero and 1% of MRSA strains, respectively. Resistance to other non beta lactam antibiotics was also high. No MRSA strains were found to be resistant to vancomycin and tegicycline. CONCLUSION: Mupirocin resistance was found to be very low among local clinical isolates of MRSA. Its judicious use to decolonize nasal carriers should be promoted among hospitalized patients to avoid further transmission and infections due to prevalent endemic MRSA strains in any health care setting. Concomitantly, regular surveillance and effective infection control initiatives are desirable to reduce the incidence of health care associated infections due to MRSA and also of mupirocin resistance.