Correction to: Molecular characterization of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates identifies local transmission of infection in Kuwait, a country with a low incidence of TB and MDR-TB.

The original publication of this article [1] contained few erroneous paragraphs and errors in Table 1 and Table 2. The first four paragraphs are in the 'Results' section while the last four paragraphs are in the 'Discussion' section. The errors in Table 1 involve the number of isolates tested for pyrazinamide and pyrazinamide susceptible isolates, ethambutol-susceptible isolates with a mutation and number of resistant isolates with a mutation for streptomycin. The error in Table 2 involves wrong codon number for a mutation in isolate KM17-01 in Cluster XII for gidB gene. The updated informations have been indicated in bold and also refer corrected Tables 1 and 2.

Health Care-Associated Infections in a Neurocritical Care Unit of a Developing Country.

BACKGROUND: Health care-associated infections (HAIs) in intensive care units (ICUs) specialized for neurocritical care (neurocritical care units [NCCUs]) are serious yet preventable complications that contribute significantly to morbidity and mortality worldwide. However, reliable data are scarcely available from the developing world. We aimed to analyze the incidence, epidemiology, microbial etiology, and outcomes of HAIs in an NCCU of a tertiary care teaching hospital in a high-income, developing country. METHODS: In this 3-year retrospective cohort study, all patients admitted to the NCCU at the Ibn Sina Hospital in Kuwait for ≥ 2 calendar days were included. Patient demographics, hospitalization, and details of ICU-acquired infections were evaluated. Patient-related outcomes included hospital and ICU length of stay (LOS) and in-hospital mortality. RESULTS: Among 913 patients with a total of 4921 ICU days, 79 patients had 109 episodes of HAIs. The overall incidence rate and incidence density of HAIs were 11.9/100 patients and 22.1/1000 ICU days, respectively. Multiple episodes of infection were documented in 29% of patients. The most prevalent infections were urinary tract infections (UTIs; 40/109 [37%]), bloodstream infections (30/109 [28%]), and pneumonia (16/109 [15%]). Seventy-six percent of infections were device-associated infections. A total of 158 pathogens were isolated, of which 109 were Gram-negative bacteria. Of the 40 Gram-positive bacteria, 22 were staphylococci. Seven infections were due to Clostridium difficile. There were 15 Staphylococcus aureus isolates, 47% of which were methicillin resistant. Two episodes of UTIs were due to Candida species. There were 84 Enterobacteriaceae isolates, 24% of which were extended-spectrum ß-lactamase producers. All Pseudomonas aeruginosa isolates were susceptible to aminoglycosides and carbapenems. Klebsiella species were the most common pathogen (45/158 [28%]), causing pneumonia (11/33 isolates [33%]), bloodstream infections (12/37 isolates [32%]), and UTIs (16/52 isolates [31%]). One episode of bloodstream infection was due to multidrug resistant Acinetobacter baumanii which was susceptible only to colistin. Only pneumonia was independently associated with mortality, while all HAIs that occurred were significantly associated with a prolonged ICU LOS. CONCLUSIONS: This is the first HAI surveillance study in an NCCU in Kuwait, and our results demonstrate the burden of HAIs on the neurologically injured patient, regardless of the site of infection. The high prevalence and resistant profile of HAIs in an NCCU in a developing country relative to a developed country has important implications for patient safety and emphasizes the need to strengthen collaboration between NCCU teams and infection control teams to prevent serious complications in this setting.

Molecular characterization of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates identifies local transmission of infection in Kuwait, a country with a low incidence of TB and MDR-TB.

BACKGROUND: Increasing incidence of multidrug-resistant Mycobacterium tuberculosis infections is hampering global tuberculosis control efforts. Kuwait is a low-tuberculosis-incidence country, and ~ 1% of M. tuberculosis strains are resistant to rifampicin and isoniazid (MDR-TB). This study detected mutations in seven genes predicting resistance to rifampicin, isoniazid, pyrazinamide, ethambutol and streptomycin in MDR-TB strains. Sequence data were combined with spoligotypes for detecting local transmission of MDR-TB in Kuwait. METHODS: Ninety-three MDR-TB strains isolated from 12 Kuwaiti and 81 expatriate patients and 50 pansusceptible strains were used. Phenotypic drug susceptibility was determined by MGIT 460 TB/960 system. Mutations conferring resistance to rifampicin, isoniazid, pyrazinamide, ethambutol and streptomycin were detected by genotype MTBDRplus assay and/or PCR sequencing of three rpoB regions, katG codon 315 (katG315) + inhA regulatory region, pncA, three embB regions and rpsL + rrs-500-900 regions. Spoligotyping kit was used, spoligotypes were identified by SITVIT2, and phylogenetic tree was constructed by using MIRU-VNTRplus software. Phylogenetic tree was also constructed from concatenated sequences by MEGA7 software. Additional PCR sequencing of gidB and rpsA was performed for cluster isolates. RESULTS: Pansusceptible isolates contained wild-type sequences. Mutations in rpoB and katG and/or inhA were detected in 93/93 and 92/93 MDR-TB strains, respectively. Mutations were also detected for pyrazinamide resistance, ethambutol resistance and streptomycin resistance in MDR-TB isolates in pncA, embB and rpsL + rrs, respectively. Spoligotyping identified 35 patterns with 18 isolates exhibiting unique patterns while 75 isolates grouped in 17 patterns. Beijing genotype was most common (32/93), and 11 isolates showed nine orphan patterns. Phylogenetic analysis of concatenated sequences showed unique patterns for 51 isolates while 42 isolates grouped in 16 clusters. Interestingly, 22 isolates in eight clusters by both methods were isolated from TB patients typically within a span of 2 years. Five of eight clusters were confirmed by additional gidB and rpsA sequence data. CONCLUSIONS: Our study provides the first insight into molecular epidemiology of MDR-TB in Kuwait and identified several potential clusters of local transmission of MDR-TB involving 2-6 subjects which had escaped detection by routine surveillance studies. Prospective detection of resistance-conferring mutations can identify possible cases of local transmission of MDR-TB in low MDR-TB settings.

A 4-year prospective study of septicemia in pediatric surgical patients at a tertiary care teaching hospital in Kuwait.

BACKGROUND: Critically ill children are at high risk for developing nosocomial infections that contributes to death in 4% of all pediatric intensive care unit admissions. This prospective study was undertaken to determine the prevalence of septicemia in the pediatric surgery department of a large tertiary care teaching hospital in Kuwait and to evaluate the risk factors, the microbial etiology, and the antimicrobial susceptibility pattern of the isolated microorganisms. METHODS: All patients admitted to the pediatric surgery department from January 2001 until December 2004 with the diagnosis of septicemia were included in the study, and the microbiologically proven cases were then analyzed. The patients' demographics and risk factors for sepsis were recorded. All positive blood cultures were subjected to identification and antimicrobial susceptibility testing by VITEK 2(bioMerieux, Marcy l'Etoile, France). RESULTS: Of 3408 patients suspected to have septicemia, 78 (2.3%) patients developed microbiologically documented septicemias, 26% of those were low-birth weight patients, and 82% were patients with congenital anomalies; 87% of those needed surgical intervention. More than 50% were admitted to the intensive care unit, and 80.5% needed ventilatory support. Fifty-seven percent had early onset septicemia. Gram-positive and gram-negative bacteria accounted for 54% and 39% of the septicemia cases, respectively, whereas Candida spp was responsible for 7%. More than 50% of the staphylococci were resistant to cloxacillin, and all gram-positives were uniformly susceptible to glycopeptides and linezolid. Gram-negative bacteria showed variable resistance to cephalosporins (65%), piperacillin/tazobactam (29%), and carbapenems (11%). The attributable mortality rate for these septic episodes was 19% mainly because of gram-negative bacteria and Candida. CONCLUSION: The main etiologic agents of neonatal septicemia were coagulase-negative Staphylococcus, Pseudomonas aeruginosa, and members of the family Enterobacteriaceae. Empirical therapy with piperacillin/tazobactam or carbapenems for gram-negative septicemia and glycopeptides for gram-positive septicemia was effective.

Fatal strongyloidiasis in three kidney recipients in Kuwait.

OBJECTIVE: It was the aim of this study to report 3 rare fatal cases of strongyloidiasis in Kuwaiti renal transplant patients. CLINICAL PRESENTATION AND INTERVENTION: All 3 cases received allografts from cadaveric donors of Asian origin, the first 2 from an Indian (transplanted on the same day) and the third from a Bangladeshi. In all 3 cases, Strongyloides stercoralis larvae were first isolated from bronchoalveolar lavage. All 3 patients were on immunosuppressive therapy which included prednisolone, thereby leading to the hyperinfection syndrome. All patients presented with gastrointestinal symptoms (abdominal pain, vomiting, diarrhea, constipation and paralytic ileus), as well as pulmonary symptoms (cough, dyspnea and blood-stained sputum). Albendazole 800 mg twice daily orally was started. Cyclosporine A was started after discontinuing prograf. The patients continued to deteriorate with a fall in blood pressure and platelets. All 3 patients died from adult respiratory distress syndrome following hyperinfection with S. stercoralis. CONCLUSION: Hyperinfection with S. stercoralis is a rare but preventable complication of immunosuppressive therapy. A high index of suspicion is required for the diagnosis of this infection. Persistent examination of sputum, bronchial washings and upper intestinal aspirates should be done as part of surveillance following cadaveric renal transplantation. Adult respiratory distress syndrome is indeed a red flag in patients who are on steroids, not on cyclosporine and receiving a kidney from donors in endemic countries of S. stercoralis.

Implications of Streptococcus pneumoniae penicillin resistance and serotype distribution in Kuwait for disease treatment and prevention.

Streptococcus pneumoniae causes serious infections. Treatment is difficult because of the emergence of penicillin resistance in S. pneumoniae. Pneumococcal vaccines offer the promise of control and prevention of pneumococcal infections. Serotype prevalence and penicillin susceptibility data for a country will predict the usefulness of the vaccines in that country. In Kuwait, the 23-valent polysaccharide and the 7-valent conjugate vaccines are being used without knowledge of the prevalent serotypes in the country. To obtain the necessary background information, data on penicillin susceptibility and serogroups were obtained from 397 consecutive clinical isolates collected during 2004 and 2005. Two hundred fifty-three isolates (64%) were penicillin resistant, and resistance was significantly higher in patients < or =15 years old and among the upper respiratory tract and eye isolates. The most common serotypes were 23F, 19F, 6A, 6B, 14, and 19A. Among the penicillin-resistant strains, the most common serotypes were 23F, 19F, 6B, 14, and 9A. Among the invasive strains, the most common serotypes were 14, 23F, 19A, and 9V. The polysaccharide vaccine gave 82% coverage against invasive infections in all age groups >2 years. The coverage of the 7-valent conjugate vaccine against invasive serotypes in children < or =2 years old was 55%. This moderate coverage by the conjugate vaccine against invasive infections in children necessitates a revised strategy on the use of the present conjugate vaccine and shows the need for formulation of an improved vaccine for superior coverage for Kuwait and possibly other countries of the Arabian Gulf.

Discrepancy in antimicrobial susceptibility test results obtained for oral streptococci with the Etest and agar dilution.

A total of 270 viridans group streptococci (VS) isolated from healthy children, identified to the species level, were tested for their susceptibilities to penicillin, imipenem, erythromycin, and vancomycin. A total of 270 isolates and 1,080 organism-antibiotic combinations were evaluated. The overall susceptibility rates of all isolates obtained by the Etest (ET) versus agar dilution (AD) were 60.4% versus 61.8% for penicillin, 63.8% versus 63.9% for erythromycin, 90.6% versus 96% for vancomycin, and 99.1% versus 96.0% for imipenem, respectively. Major discrepancies occurred in the testing of the susceptibility of Streptococcus mutans to vancomycin, with 59.5% (ET) versus 100% (AD), followed by S. salivarius, with 84.1% versus 100%; S. oralis, with 82.1% versus 96.4%; and S. mitis, with 90% versus 100%, respectively. There were also differences in the rates of susceptibility of S. mutans, 66.5% (ET) versus 85.1% (AD), and S. intermedius, 82.9% versus 72.1%, respectively, to penicillin. General agreement between the results of ET and AD was obtained for 973 organism-antibiotic combinations out of 1,080 antibiotic combinations, i.e., 90.1%. Very major errors were found for 6.8% of isolates, and major errors were found for 3.2% of isolates; the minor errors were negligible. Agreement between the results of the two methods was 98.7% for penicillin, 94.6% for vancomycin, 96.9% for imipenem, and 99.9% for erythromycin. The highest rate of very major errors was for vancomycin, at 5.4%. The ET appears to be as efficient as AD for susceptibility testing of VS, except for vancomycin, where very major errors in the results were relatively high.

Species distribution and antifungal susceptibility of Candida bloodstream isolates in Kuwait: a 10-year study.

Bloodstream infections due to Candida species are important complications in severely ill hospitalized patients. This study presents data on species distribution and antifungal susceptibility profiles of Candida bloodstream isolates obtained from Kuwait during a 10-year period. All the bloodstream isolates were identified to species level by the germ tube test and carbohydrate assimilation profile using the VITEK 2 yeast identification system. Using E-test strips for amphotericin B, fluconazole, 5-flucytosine and voriconazole, MICs were determined on RPMI agar supplemented with 2% glucose. The MIC breakpoints for resistance were based on Clinical and Laboratory Standards Institute criteria or those published by reference laboratories, and were as follows: amphotericin B, >1 microg ml-1; fluconazole, >or=64 microg ml-1; 5-flucytosine, >or=32 microg ml-1; and voriconazole, 4 microg ml-1. In all, 607 bloodstream yeast isolates were obtained over the past 10 years in Kuwait. Candida albicans was the predominant species (39.5%), followed by Candida parapsilosis (30.6%), Candida tropicalis (12.4%), Candida glabrata (5.6%) and Candida krusei (1.6%). All C. albicans, C. tropicalis and C. glabrata isolates were susceptible to amphotericin B. Of 186 isolates of C. parapsilosis tested, only four (2%) exhibited an MIC for amphotericin B of >1 microg ml-1. Resistance to fluconazole was observed in nine (3.8%) C. albicans isolates, two (5.8%) C. glabrata isolates and four (40%) C. krusei isolates. Resistance to 5-flucytosine was observed in two (0.8%) C. albicans isolates, seven (9.3%) C. tropicalis isolates, three (1.6%) C. parapsilosis isolates and all ten (100%) C. krusei isolates. All the isolates of C. albicans, C. tropicalis, C. parapsilosis, C. glabrata and C. krusei were susceptible to voriconazole, including those resistant to fluconazole. Although amphotericin B and fluconazole are widely used in clinical practice in Kuwait, resistance to these drugs remained low.

Increasing prevalence of antimicrobial resistance in Streptococcus pneumoniae in Kuwait: implications for therapy.

From 2001 to 2004, 824 consecutive Streptococcus pneumoniae isolates obtained from all the teaching hospitals and primary-care centers serving all of Kuwait were studied for their susceptibility to a number of antibiotics. Of these, 514 (63%) were resistant to penicillin, 55% of which were of intermediate resistance, with a minimum inhibitory concentration (MIC) of 0.16-1 microg/ml, and 8% were of full resistance (MIC > or =2 microg/ml). The prevalence of penicillin resistance was significantly higher among the eye isolates than the rest of the isolates combined. Resistance across all classes of antibiotics was more common with the isolates from blood and cerebrospinal fluid (CSF). Decreased susceptibility to ceftriaxone, cefotaxime, imipenem, meropenem, erythromycin, and cotrimoxazole was observed in 15%, 12.8%, 10.2%, 8.6%, 42%, and 69% of isolates, respectively. Multidrug-resistant S. pneumoniae was isolated mostly from invasive diseases. There has been a remarkable increase in the prevalence of drug-resistant S. pneumoniae isolates in Kuwait over the past 20 years, and Kuwait has thus joined the league of hyperendemic countries for penicillin-resistant S. pneumoniae (PRSP). It is also conceivable that Kuwait, with a large expatriate population of workers, may serve as a focal point for further dissemination of resistant clones to the rest of the world. These data are unique because they are representative of the whole Kuwaiti population.

Prevalent PCR ribotypes of clinical and environmental strains of Clostridium difficile isolated from intensive-therapy unit patients in Kuwait.

Ninety-five isolates of Clostridium difficile from symptomatic and asymptomatic patients and 18 from their environment in the intensive-therapy units (ITUs) of four teaching hospitals in Kuwait were typed by PCR amplification of rRNA intergenic spacer regions (PCR ribotyping). A total of 32 different ribotypes was detected among the clinical isolates. The predominant ribotypes from the clinical isolates were types 097 and 078, which accounted for approximately 40 % of all isolates in the ITUs in Kuwait. Ribotypes 097 (toxigenic), 078 (toxigenic) and 039 (non-toxigenic) were three distinct clones that were circulating in all four hospitals. Ribotypes 097, 078 and 076 (i.e. 50 % of isolates from symptomatic patients) were the predominant isolates associated with C. difficile-associated disease (CDAD). The environmental isolates belonged to a diverse range of ribotypes, with no particular types common to all the hospitals. Ribotype 078 was found only in the patient environment in Mubarak hospital, while ribotype 097 was restricted to Amiri hospital. The hospital environment occupied by symptomatic as well as symptom-free patients was contaminated with C. difficile. Eight new strains that did not match any in the PCR ribotype library established at the PHLS Anaerobe Reference Unit, Cardiff, UK, were assigned ribotypes 105, 125, 128, 129, 131, 134, 140 and 141. These findings show that the isolates associated with CDAD in Kuwait are different from those found in the UK and some other European countries.

In vitro activity of 15 antimicrobial agents against clinical isolates of Clostridium difficile in Kuwait.

A total of 73 clinical isolates of Clostridium difficile isolated from stool/rectal swabs of patients admitted to the intensive care units at Mubarak Hospital, Ibn Sina Hospital Burn unit and Haematology wards at the Kuwait Cancer Control Centre, were investigated for their susceptibility to 15 antibiotics using the Etest. Amoxycillin-clavulanic acid, ampicillin, meropenem, metronidazole, penicillin, piperacillin, piperacillin/tazobactam, teicoplanin and vancomycin had excellent activities with MIC(90)s of 0.38, 0.5, 1, 0.19, 1.5, 2, 3, 0.25 and 0.75 mg/l, respectively. Of the 73 C. difficile isolates, 86% were resistant to imipenem (MIC(90) >32 mg/l) and almost 97% were resistant to trovafloxacin (MIC(90)>256 mg/l). Forty eight percent of the isolates were resistant to clindamycin. A total of 18 isolates were highly clindamycin-resistant with an MIC of >256 mg/l; 10 of these were toxin producers. Multiple antibiotic resistance (two or more antibiotics) was noted in 63 isolates. These were more common among the toxigenic strains than the non-toxigenic strains by a ratio of 2.5:1.