Effect of the introduction of pneumococcal conjugate vaccines on serotype prevalence in Kuwait and Saudi Arabia.

BACKGROUND: Streptococcus pneumoniae infection is a major cause of morbidity and mortality. Although pneumococcal disease burden in Kuwait and Saudi Arabia is considered high, comprehensive surveillance data on pneumococcal conjugate vaccine (PCV) effects are lacking. METHODS: Sterile isolates from patients in Kuwait (2003-2016) and Saudi Arabia (aged ≤5 years, 2000-2010; all patients, 2011-2015) were included. Serotyped isolates were classified by inclusion in the 7-valent (PCV7) or 13-valent PCV (PCV13); isolates of other serotypes were classified as "non-PCV13". Isolate frequency (number of isolates/year) and classification of isolates according to vaccine type were assessed by period (before PCV, after PCV7, and after PCV13 introduction). RESULTS: In Kuwait, the frequency of collected isolates was highest after PCV7 introduction. Decreased frequency of PCV7 serotypes was seen after PCV13 introduction compared with before PCV and after PCV7 introduction. Increased frequency of the 6 additional serotypes in PCV13 and non-PCV13 serotypes was observed after PCV7 introduction with a subsequent decrease in the 6 additional serotypes in PCV13 and non-PCV13 serotypes after PCV13 introduction. The percentage of isolates of vaccine serotypes in Kuwait decreased over time. In Saudi Arabia, the frequency of collected isolates was highest after PCV7 introduction. An increased frequency of PCV7 serotypes was observed after PCV7 introduction, with a further decrease after PCV13 introduction. For the 6 additional serotypes in PCV13, an increased frequency was seen after PCV7 and PCV13 introduction compared to before PCV introduction. For non-PCV13 serotypes, an increased frequency was observed after PCV13 introduction compared to after PCV7 introduction. The percentage of isolates covered by PCV13 serotypes was similar across periods, while a substantial decrease in isolates covered by PCV7 was seen after PCV13 introduction. CONCLUSION: PCVs in Kuwait and Saudi Arabia resulted in decreased frequency of some vaccine serotypes and an emergence of some non-PCV13 serotypes. Further investigation is warranted.

Comparison of two molecular methods and an automated liquid culture system for the early detection of Mycobacterium tuberculosis from both pulmonary and extrapulmonary specimens in Kuwait.

OBJECTIVE/BACKGROUND: Molecular methods for the detection of Mycobacterium tuberculosis (MTB) are widely used for the early diagnosis of tuberculosis (TB). The objectives of this study were to evaluate the performance of two molecular techniques for the detection of MTB for both pulmonary and extrapulmonary specimens in comparison with conventional culture techniques in Kuwait and to correlate the results with clinical and histopathological diagnosis. METHODS: A total of 9,594 consecutive pulmonary (n=5,597) and extrapulmonary (n=3,997) specimens received by the Kuwait National TB Reference Laboratory from November 2011 to December 2015 were processed for direct smear microscopy for acid-fast bacilli using a Zhiel-Neelsen stain, Xpert MTB/RIF assay, ProbTec polymerase chain reaction (PCR), and growth in fully automated MGIT 960 system tubes. The clinical and histopathological diagnoses were correlated with the results. RESULTS: For pulmonary specimens, the overall sensitivity and specificity of both molecular methods together were 90.7% and 99.7%, respectively. The sensitivity and specificity of the Xpert MTB/RIF assay were 90.1% and 99.4%, respectively. The sensitivity and specificity of ProbTec PCR were 86% and 99.6%, respectively. For extrapulmonary specimens, the overall sensitivity and specificity of both molecular methods together were 87% and 97.8%, respectively. The sensitivity and specificity of Xpert MTB/RIF assay were 89.5% and 97.2%, respectively. The sensitivity and specificity of ProbTec PCR were 73% and 97.8%, respectively. When clinical and histopathological correlations were made with the assumed false-positive results from both molecular methods, the corrected sensitivity and specificity for pulmonary specimens were 91% and 99.9%, respectively, and 89.6% and 99.8% for extrapulmonary specimens, respectively. CONCLUSION: The performance of the Xpert MTB/RIF assay was superior to ProbTec PCR for the early detection of MTB from both pulmonary and extrapulmonary specimens.

The technical aspects and clinical significance of detecting extended-spectrum beta-lactamase-producing Enterobacteriaceae at a tertiary-care hospital in Kuwait.

Extended-spectrum beta-lactamase (ESBL) production by Enterobacteriaceae is an emerging problem. This 3-year prospective study was undertaken to determine the prevalence of such enzymes among the clinically significant isolates of the Enterobacteriaceae family gathered from patients, and to evaluate the different techniques for their detection as well as their clinical significance. Members of the Enterobacteriaceae family isolated from blood, inhibited by the third-generation cephalosporins with minimum inhibitory concentrations (MICs) of < or =2 microg/ml and MIC < or =8 microg/ml and isolates from other sources inhibited by MIC < or =8 microg/ml were also investigated for ESBL production by VITEK2 and E test. Their clinical significance in septicemic patients was analyzed. Out of 3,215 isolates, 1018 (31.7%) were ESBL-producers by both VITEK2 and E test. Of these, 428 (42%) were Klebsiella pneumoniae and 376 (37.0%) were Escherichia coli with overall prevalence rates of 13.3% and 11.7%, respectively. There were a total of 184 septicemic patients infected by ESBL-producing Enterobacteriaceae out of which 134 (73%) needed modification of therapy; most (58%) of these patients were initially on third-generation cephalosporin therapy. A total of 58 (31.5%) patients were infected by ESBL-producing blood isolates which were inhibited by cefotaxime/ceftriaxone at MICs =8 microg/ml (within the susceptibility range). Resistance to both aminoglycosides and quinolones were significantly higher among ESBLproducing isolates compared to non-producers (P <0.05). This study highlights a high prevalence of ESBL-producing Enterobacteriaceae in a major tertiary teaching hospital in our country and demonstrates that almost a third of the ESBL-producing Enterobacteriaceae blood isolates would have been released as susceptible by routine susceptibility testing; a finding inimical to optimal therapeutic success.

Surveillance of antibacterial resistance in Staphylococcus aureus isolated in Kuwaiti hospitals.

OBJECTIVE: To investigate the prevalence of antibiotic resistance among Staphylococcus aureus isolated in Kuwaiti hospitals. MATERIALS AND METHODS: S. aureus were isolated and identified following standard microbiological methods. Antibacterial susceptibility test was performed by disk diffusion and the measurement of minimum inhibitory concentration with E-test strips. RESULTS: A total of 1,846 S. aureus isolates were analyzed from 13 hospitals between 1 March and 30 October 2005. They were isolated from 1,765 (95.6%) inpatients and 81 (4.4%) outpatients. Methicillin resistance was detected in 588 (32.0%) of the isolates. The methicillin-resistant S. aureus (MRSA) consisted of 461 (78%) multiresistant and 127 (22%) nonmultiresistant isolates. The nonmultiresistant MRSA consisted of epidemic MRSA-15 and community-associated MRSA. The community-associated MRSA was detected in all hospitals with MRSA, indicating its establishment in Kuwaiti hospitals. The proportion of isolates resistant to gentamicin, kanamycin, erythromycin, tetracycline, ciprofloxacin, fusidic acid and trimethoprim was higher among MRSA than methicillin-susceptible S. aureus (MSSA) isolates. Twenty-four and 22% of MRSA and MSSA isolates, respectively, expressed reduced susceptibility to vancomycin (minimum inhibitory concentration = 3-4 mg/l). CONCLUSION: The study revealed the presence of methicillin resistance in 32% of S. aureus isolated in Kuwaiti hospitals and revealed an increase in the number of MRSA and MSSA with reduced susceptibility to vancomycin.

Septicaemia in scald and flame burns: appraisal of significant differences.

One hundred and sixty burn patients suffering from septicaemia, hospitalized in the Al-Babtain Centre burns unit, Kuwait, between June 1992 and May 2001, were studied. Thirty-two patients (20%) had scalds and 128 (80%) flame burns, thus representing a ratio of 1:4 among septicaemic patients. There were 20 males (62.5%) in the scald group, compared to 73 (57%) with flame burns. Flame burns were significantly higher (p < 0.01) among non-Kuwaiti patients. The mean ages of the scald and flame burn patients were respectively 6.2 and 31.5 yr. The mean total body surface area burn in scalds was 20% and in flame burns 49%, which was significantly higher (p < 0.001). The 34 septicaemic episodes in 32 scald patients and 212 such episodes in 128 flame burn patients showed a significantly higher incidence in the latter group. The majority of septicaemic episodes, in scalds (82.4%) and flame burns (57.6%), were due to gram-positive organisms, mainly methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis. A significantly increased number of episodes were due to S. aureus (p < 0.001) and Enterococcus (p < 0.05) in scald patients. More surgical operations were performed in flame burn patients and survival increased significantly with an increasing number of grafting sessions (p < 0.001). The mean hospital stay in flame burn patients (56 days) was significantly higher than in scald patients (23 days) (p < 0.001). It is significant to record that all the 38 deaths (29.7%) were in flame burn septicaemic patients (p < 0.001). The scald and flame burn patients were quite distinct in their demographic and clinical characteristics. The flame burn patients were more vulnerable to septicaemia, with a high risk of mortality.

Significance of atypical pathogens among community-acquired pneumonia adult patients admitted to hospital in Kuwait.

OBJECTIVES: The aim of this study is to determine the microbial etiology and severity of community-acquired pneumonia (CAP) in Kuwait. SUBJECTS AND METHODS: The severity of consecutive adult CAP cases admitted to 3 hospitals over a 1-year period was classified according to the Pneumonia Outcome Research Team (PORT) severity index. The microbial etiology was determined using standard methods for bacteria and serological tests for atypical and viral pathogens. RESULTS: The study population was 124 of the 135 admissions; 63 female, 61 male; mean age 41.3+/-18 years. The severity class distribution was: class I 31%, class II 37%, class III 17%, class IV 13%, and class V 2%. Etiological agents were identified from 44 patients (35%), with one pathogen in 31 (25%), two in 9 (7%), and three or more in 4 (3%). The most common pathogens identified were: Mycoplasma pneumoniae in 14 patients (11%), Legionella pneumophila in 10 (8%), Chlamydia pneumoniae in 8 (6%), influenza B virus in 8 (6%), influenza A virus in 5 (4%), Haemophilus influenzae in 4 (3%), Streptococcus pneumoniae in 3 (2%), Staphylococcus aureus in 3 (2%), gram-negative enterobacteria in 5 (4%), Moraxellacatarrhalis in 2 (2%), and viruses in 4 (3%). The yields from laboratory tests were 48% for paired serology, 20% from adequate sputum sample, and 3% from blood culture. CONCLUSION: Our study shows that a large percentage of mild CAP cases are admitted to hospitals in Kuwait. Atypical pathogens have a significant role in the etiology of CAP. There is overtreatment of CAP with a combination treatment consisting mainly of third-generation chephalosporins and macrolides.

Hospital-acquired Clostridium difficile infection amongst ICU and burn patients in Kuwait.

OBJECTIVES: To prospectively study the prevalence of nosocomially acquired Clostridium difficile, a major cause of diarrhoea in hospitalized patients, in the intensive care units (ICUs) and burn unit (BUs) of three teaching hospitals in Kuwait. METHODS: During a 1-year prospective study, stool/rectal swabs were obtained from 344 patients admitted into the ICUs of Mubarak Hospital (ICU-1), the Kuwait Cancer Control Centre (ICU-2), and the BU of Ibn Sina Hospital. The presence of C. difficile and/or its toxin was detected by serially culturing the specimens on differential, selective and enriched media and the use of TOX-A/B test, on admission and at subsequent 1-weekly interval until discharge. RESULTS: Out of the 344 patients admitted into these units, over a study period of 1 year, only 263 (77%) were evaluable. All of them had negative stool culture/toxin on admission. Overall, 25 (9.5%) of these 263 patients acquired C. difficile during their hospitalization. Thirteen (7%) of 187 patients acquired C. difficile in ICU-1, 9 (36%) of 25 on ICU-2 and 3 (5.9%) of 51 patients in BU. Eight (32%) developed diarrhoea attributable only to C. difficile and/or toxin, and the remaining 17 (68%) were asymptomatic: none had pseudomembranous colitis. The diarrhoea in these patients was associated with antibiotic use, the main trigger-antibiotics being the third-generation cephalosporins. Acquisition occurred within 4-53 days of admission, with the majority occurring in the first 15 days. CONCLUSION: Overall, the prevalence of hospital-acquired C. difficile infection/colonization was less than 10%. The use of third-generation cephalosporins was high and was related to the development of diarrhoea. Once acquired, diarrhoea developed in about one third of C. difficile-positive cases, an indication that C. difficile infection/colonization endemic in the hospital ICUs studied is usually transmitted among the hospitalized patients.

VEB-1-like extended-spectrum beta-lactamases in Pseudomonas aeruginosa, Kuwait.

Two clinical Pseudomonas aeruginosa isolates from patients in intensive care units in Kuwait were resistant to expanded-spectrum cephalosporins and showed a synergistic effect between ceftazidime and clavulanic acid. This is the first report of extended-spectrum enzymes from nosocomial isolates from the Middle East.

Prevalence of penicillin-resistant Streptococcus pneumoniae in Kuwait.

The worldwide incidence of penicillin-resistant Streptococcus pneumoniae has increased at an alarming rate during the past decade. However, there has been little published data about the extent of this problem in Kuwait. The present study was undertaken to ascertain the preponderance of S. pneumoniae, either resistant or intermediate-resistant to penicillin, other beta-lactams and non-beta-lactam antimicrobials in Kuwait. Two hundred and fifty fresh isolates from as many patients suffering from different clinical conditions were collected from all clinics and hospitals in Kuwait. Optochin sensitivity and bile solubility tests reconfirmed these. Susceptibility testing to penicillin, ampicillin, cefuroxime, ceftriaxone, cefotaxime, imipenem, erythromycin, chloramphenicol, ciprofloxacin and vancomycin was done using E-test strips and to oxacillin, tetracycline, trimethoprim and amoxicillin-clavulanate by disc diffusion technique. Full and intermediate resistance to penicillin was observed in 1.6% and 52.8% of the isolates respectively. Full resistance to third-generation cephalosporins ranged from 0.4% to 3.2%, however, intermediate resistance to these antibiotics varied between 18.8% and 21.2%. Ampicillin resistance was noted in 0.8%, but 40.4% of isolates were intermediately resistant. However, only 0.4% of the isolates showed either intermediate or full resistance to amoxicillin-clavulanate. Resistance to imipenem was observed in 0.4% and intermediate to 13.6% of the organisms. The rates of S. pneumoniae resistant to chloramphenicol, erythromycin, tetracycline and trimethoprim were between 8.4% and 37.6% and intermediate resistance between 1.2% and 17.6% while only 0.4% showed resistance to ciprofloxacin and none to vancomycin. Multiresistance to both beta-lactam and non-beta-lactam antibiotics was observed in 52% of the penicillin-resistant isolates.

Candidemia in pediatric surgery patients.

Candida spp. are the fourth leading cause of bloodstream infection. While the literature on neonatal candidemia is abundant, its prevalence in pediatric surgery cases is hardly mentioned. This study was carried out over a 5-year period to evaluate the prevalence of candidemia in pediatric surgery intensive care unit patients (ICU), and to examine both the neonatal and hospital risk factors for developing candidemia in comparison to control groups of patients with either no infection or with bacteremia, type and outcome of therapy. A total of 1,359 pediatric surgery patients admitted to the ICU and high dependency unit (HDU) were included in the study. Using relevant specimens from them, a microbiological survey was carried out on admission and weekly thereafter. Twenty-five patients developed candidemia during the study period. Twenty-one of them were admitted to ICU. Nine were low birth weight and immature neonates. All 25 patients had underlying disease, most involving the gastroentestinal tract and requiring surgical intervention. All patients had been given broad-spectrum beta-lactam antibiotics with or without aminoglycosides and an anti-anaerobic drug prior to candidemia. The data show that patients who were not infected had very few risk factors that could predispose to candidemia. The bacteremic group of patients had more risk factors: mainly ICU stay, prior antibiotic therapy or GI surgery. The candidemia patients outnumbered these two groups in both neonatal and hospital risk factors. Twenty-three candidemia patients had received amphotericin B and 2 had fluconazole. Seventeen of them improved and the rest expired during therapy. Fourteen of the Candida isolated were C. albicans while the rest belonged to other Candida spp. dominated by C. parapsilosis. In conclusion, candidemia was infrequent in pediatric surgery patients. ICU stay, GI surgery and prior broad-spectrum antibiotic therapy were important risk factors.

Resistance patterns of Pseudomonas aeruginosa to carbapenems and piperacillin/tazobactam.

Pseudomonas aeruginosa is a major problem as a multiresistant nosocomial pathogen, especially in burns and other immunocompromised patients in our hospital. The present prospective study, conducted between June 1996 and December 1997, was aimed at determining the extent of its resistance against highly active antipseudomonal drugs, such as carbapenems (imipenem and meropenem) and ureidopenicillin with beta-lactamase inhibitor (piperacillin/tazobactam); existence of any cross resistance or difference in susceptibility between imipenem and meropenem; and to compare the activity of piperacillin/tazobactam with the two carbapenems against P. aeruginosa. Of the 357 P. aeruginosa isolates tested from 188 patients 37 (10.4%) were resistant to imipenem, 21 (5.9%) to meropenem and 50 (14%) to piperacillin/tazobactam. Cross resistance between the two carbapenems was observed in 5.9% of the isolates. Sixteen (43%) of the imipenem-resistant isolates were susceptible to meropenem but the reverse was observed in none. Amongst the 50 piperacillin/tazobactam-resistant isolates cross resistance with the two carbapenems was observed in 18 (36%) and in 9 (18%) only with imipenem; 23 (46%) were susceptible to both. Our results indicate that P. aeruginosa is least resistant to meropenem followed by imipenem and piperacillin/tazobactam. Cross resistance between the carbapenems and between carbapenems and piperacillin/tazobactam was found. The study further suggests that burns, cardiac-neuro-pediatric surgical, cancer and transplant patients are more susceptible to acquiring infection due to multiresistant P. aeruginosa than other types of patients and common infection sites were wounds, respiratory tract, urine, blood and intravascular lines.

Beta-haemolytic Streptococcus infection in burns.

Group A beta haemolytic Streptococcus has been one of the most serious infections in the burn patients resulting in severe cellulitis and sepsis. Penicillin has been used ever since its introduction as prophylaxis against these conditions. Penicillin prophylaxis was used in our burn unit as well without any serious evaluation until December 1992. This prospective study was therefore, undertaken to evaluate the incidence of beta haemolytic Streptococcus infection in burn patients, and its clinical outcome over a period of 5 years in the absence of prophylaxis with penicillin. 14 of the 1213 burn patients admitted to the Al-Babtain Centre for Plastic Surgery and Burns from January 1993 to December 1997 had either colonization or infection with Streptococcus spp. Their mean age was 15 years (range 1 month to 52 years) and the mean burn surface area was 20% (range 5 to 90%). Streptococci were isolated from burn wounds in 10 patients, throat in 3 and blood culture in 1. Group A Streptococcus was found in 5, group C in 3 and group D in 6 patients. In all patients except one the organisms were isolated > or =72 h post burn. The infections were successfully controlled by antibiotic and no detrimental effect was observed either on wound healing or skin graft take. There was no mortality amongst these 14 patients. The study showed that only 1.1% of the burn patients in our unit acquired Streptococcus of which only one third comprised of group A. This study thus demonstrates that the practice of penicillin prophylaxis during the first five post burn days may not be of any value and therefore, deserves discontinuation in units where the incidence of this organism is minuscule.

The increase in carbapenem use and emergence of Stenotrophomonas maltophilia as an important nosocomial pathogen.

Carbapenems, being the broadest spectrum antibiotics, may allow those organisms intrinsically resistant to these drugs to be involved more frequently in nosocomial infections. Imipenem was introduced to the specialized hospital units in Kuwait in October, 1992 and meropenem in late 1996. The main objective of this study was to observe prospectively whether, under similar laboratory conditions for microbial isolation/identification while these drugs are in use in the hospital, there is any proportional increase over time in the recovery of Stenotrophomonas maltophilia in relation to the number of yearly admissions and drug use. In addition, we also looked for categories of patients infected by S. maltophilia, type of infection and antibiotic susceptibility. There was an increase in the number of S. maltophilia isolates from 1993 to 1997 significantly correlated with the increase in year-wise consumption of carbapenems (p<0.004). No correlation was observed between yearly number of admissions and both the consumption of carbapenems (p>0.51) and isolation of the organism (p>0.59). Most isolates were from cancer, burns and cardiac patients. The commonest types of infection were wound and septicemia. The organisms were susceptible mostly to ciprofloxacin and co-trimoxazole. The study thus indicates that carbapenem use in a hospital environment may result in emergence of nosocomial infections due to multiresistant S. maltophilia in high risk patients with very limited choice of antibiotics for therapy.

Susceptibility of 497 clinical isolates of gram-negative anaerobes to trovafloxacin and eight other antibiotics.

Trovafloxacin is a novel investigational trifluoronaphthyridone antibiotic with broad-spectrum activity against Gram-positive and Gram-negative organisms. Its in-vitro activity and those of eight other antimicrobial agents were evaluated against 497 clinical isolates of Gram-negative anaerobic bacteria by the agar dilution method. Trovafloxacin had excellent activity, with a minimum inhibitory concentration (MIC) range of <0.03-4 microg/ml, against all species. Out of the 497 isolates tested, 496 (99.5%) were inhibited by a concentration of < or = 2.0 microg/ml of trovafloxacin; the remaining two strains were inhibited by a concentration of 4.0 microg/ml. The MIC50s and MIC90s were 0.12 microg/ml and 1.0 microg/ml, respectively. Meropenem, imipenem and piperacillin/tazobactam were also very active. Overall, at the MIC90s, trovafloxacin was as active as meropenem, slightly more active than metronidazole and imipenem, twice as active as amoxicillin-clavulanic acid, five times more active than piperacillintazobactam and 68 times more active than clindamycin. About 21% of the isolates were resistant to cefoxitin, 30% to clindamycin and 40% to piperacillin. Five species in the Bacteroides fragilis group of isolates were highly resistant to metronidazole (MIC >128 microg/ml). In general, the relatively more resistant species were the B. vulgatus, B. ovatus, B. thetaiotaomicron, and B. fragilis sensu stricto, in that order. All the isolates of the B. fragilis group and about 50% of the Prevotella spp. were beta-lactamase positive. Trovafloxacin certainly holds promise as an alternative drug for therapy of anaerobic infections.

The role of aggressive medical therapy along with early surgical intervention in the cure of Brucella endocarditis.

Timing of surgical intervention in Brucella endocarditis remains controversial. In this report, we review our experience in an attempt to collect some information on the best approach for this entity. From June 1992 to December 1996, 5 male patients between the ages of 20 and 35 years with Brucella endocarditis were operated on in our centre. Three of them had native valve endocarditis (NVE) and 2 with prosthetic valve endocarditis (PVE). All patients belonged to New York Heart Association (NYHA) class III-IV. All had developed anti Brucella antibodies with serum agglutination titres of > 320 and the sera tested from 3 patients were Enzyme Linked Immunosorbent Assay (ELISA) positive for anti-Brucella IgM and/or IgG antibodies. In 3 cases 2D-echocardiography showed large vegetation on the affected valve. Blood cultures were positive in 4 patients, 2 of them (one each of NVE and PVE) had the valve material culture positive for Brucella. All cases were treated with a combination of doxycycline, refampicine and gentamicin before surgery. Major indication for surgical intervention was severe haemodynamic instability which developed during the course of antibiotic therapy either early (3 cases) or late (2 cases). All patients became asymptomatic at the end of 7 days postoperatively. On the follow-up for a period of 8-51 months, all patients were in NYHA class I-II without evidence of recurrence of infection. These data suggest that in either NVE or PVE Brucella, medical therapy alone may not be sufficient due to the eventual haemodynamic deterioration secondary to valve tissue destruction or dysfunction of the prosthetic valve caused by the infective process. Therefore, a combination of aggressive medical therapy with multiple bactericidal antibiotics and early surgical intervention may result in a successful outcome, but further studies are needed to reach a reliable conclusion.