trimethoprim--sulfamethoxazole-drug-combination and Acinetobacter-Infections

Clinicians nowadays are confronted with an epidemic of multidrug-resistant (MDR) Acinetobacter infections and are forced to consider every treatment alternative, including older antibiotic agents, not conventionally used. This review aimed to evaluate the published evidence on the antimicrobial activity and clinical effectiveness of trimethoprim/sulfamethoxazole (TMP-SMX) against Acinetobacter spp. Selected in vitro studies included antimicrobial surveillance reports, microbiological studies regarding the activity of TMP-SMX against MDR Acinetobacter isolates, and clinical studies published after the year 2000. Non-susceptibility rates for Acinetobacter spp. in surveillance studies ranged from 4% to 98.2%; in 23 of 28 studies, non-susceptibility to TMP-SMX was >50% and in a subset of 15 studies non-susceptibility was >70%. In studies regarding MDR Acinetobacter spp., non-susceptibility rates ranged from 5.9% to 100%; however, 19 of 21 studies reported >70% non-susceptibility. Extensively drug-resistant Acinetobacter baumannii complex had total (100%) resistance in five of six studies. Carbapenem-resistant Acinetobacter spp. had non-susceptibility rates to TMP-SMX of >80% in 22 of 26 studies. One study on polymyxin-resistant A. baumannii showed a susceptibility rate of 54.2% (13/24). Only seven case reports evaluated TMP-SMX for Acinetobacter spp. infections, mainly in combination with other agents; all cases were deemed therapeutic successes. Although TMP-SMX is not usually active against Acinetobacter spp., it might be considered in cases where there are no other options.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Nowadays, Acinetobacter baumannii is resistant to almost all available antibiotics. The evaluation of synergistic effects between the antibiotics against this pathogen is among the efforts to counteract its antimicrobial resistance. This study aimed to evaluate possible synergistic effect of colistin and ampicillin/sulbactam (separately) with several antibiotics against clinical isolates of multi-drug resistant (MDR) A. baumannii.. Acinetobacter baumannii strains were isolated from biological samples of hospitalized patients with any type of nosocomial infection related to this pathogen. Only MDR strains (resistance to at least three classes of antibiotics including cephalosporins, fluoroquinolones, and aminoglycosides) were included in the study. After determining the minimum inhibitory concentration (MIC) of antibiotics against the isolates by broth microdilution test, the checkerboard method was used for evaluation of any possible synergistic effect of both colistin and ampicillin/sulbactam with several other antibiotics.. Twenty isolates underwent synergy test for colistin and 20 isolates for ampicillin/sulbacatam. Doxycycline (55%), azithromycin (35%), and co-trimoxazole (35%) had the most frequency of synergistic effect with colistin. On the other hand, amikacin and gentamicin (55%), doxycycline (50%), co-trimoxazole (45%), azithromycin (40%), and cefepime (40%) had the most frequency of synergistic effect with ampicillin/sulbactam. No antagonistic effect was observed for both antibiotics.. Colistin and ampicillin/sulbactam have substantial synergistic effect with several antibiotics especially doxycycline, co-trimoxazole, azithromycin, and amikacin (with ampicillin/sulbactam) against MDR strains of Acinetobacter baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Amikacin; Ampicillin; Anti-Bacterial Agents; Azithromycin; Colistin; Doxycycline; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Microbial Sensitivity Tests; Sulbactam; Trimethoprim, Sulfamethoxazole Drug Combination

Acinetobacter baumannii is a critical nosocomial pathogen. A. baumannii infections have become a grave challenge due to their ability to develop resistance to different antimicrobial agents. The current study aimed to evaluate the potential synergism and bactericidal activity of a combination of colistin and cotrimoxazole against carbapenem-resistant A. baumannii (CRAB) in a Galleria mellonella model.. Four clinical A. baumannii isolates were biochemically and molecularly identified. Their antimicrobial susceptibility levels were established and the molecular characterization of the carbapenemase-encoding genes was performed. The synergism and bactericidal effect of the colistin/cotrimoxazole combination was assessed using the checkerboard assay and time-kill experiments. An in vivo evaluation of the activity of the combination was performed using the Galleria mellonella model.. A fractional inhibitory concentration index (FICI) of ≤0.5 was found for all strains, indicating that the colistin/cotrimoxazole combination exhibited powerful synergistic activity. The combination displayed both synergistic and bactericidal activity at sub-breakpoint concentrations for all strains. Cotrimoxazole monotherapy showed the least protective activity in the G. mellonella model. The survival rate ranged from 66.7-79.2 % at 24 h and was 29.2-60.4 % at 96 h for the tested isolates. Colistin monotherapy performed better than cotrimoxazole monotherapy; the G. mellonella survival rate ranged from 77.1-97.9 %, at 24 h and from 64.5-72. % at 96 h. The colistin/cotrimoxazole combination improved G. mellonella's survival rate at 96 h remarkably in comparison to colistin or cotrimoxazole monotherapy.. Finally, the combination of colistin and cotrimoxazole appears to be a promising therapeutic option for the management of CRAB-associated infections. It is essential to assess the clinical application and the dose-response relationships of combinations such as colistin plus cotrimoxazole.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Lepidoptera; Microbial Sensitivity Tests; Trimethoprim, Sulfamethoxazole Drug Combination

This study aimed to assess the effectiveness of trimethoprim-sulfamethoxazole (TMP/SMX) as monotherapy for the treatment of carbapenem-resistant Acinobacter baumannii (A. baumannii) (CRAB) infections.. This retrospective cohort study included patients receiving TMP/SMX as the main treatment for severe infections caused by CRAB, who were matched with patients treated with colistin or ampicillin-sulbactam (AMP/SUL) by age, Charlson score, department, and source of infection. Outcomes were compared among all patients and in a subgroup of propensity-score (PS) matched patients. The PS matching was performed using a match tolerance of 0.15 with replacement.. Fifty-three patients treated with TMP/SMX and 83 matched patients treated with colistin or AMP/SUL were included. Variables that were independently significantly associated with TMP/SMX treatment included admission for infection and septic shock, while abnormal cognition on admission and intensive care unit admission were associated with colistin or AMP/SUL treatment. All-cause 30-day mortality was lower with TMP/SMX compared with the comparator antibiotics among all patients (24.5%, 13 of 53 vs. 38.6%, 32 of 83, P=0.09) and in the PS-matched subgroup (29%, 9 of 31 vs. 55.2% 16 of 29, P=0.04). Treatment failure rates were not significantly different overall (34%, 18 of 53 vs. 42.4%, 35 of 83, P=0.339) and in the PS-matched subgroup (35.5%, 11 of 31 vs. 44.8%, 13 of 29, P=0.46). Time to clinical stability and hospitalization duration were significantly shorter with TMP/SMX. Patients treated with TMP/SMX probably had less severe infections than those treated with other antibiotics, even after matching.. TMP/SMX might be a valuable treatment option for TMP/SMX-susceptible CRAB infections. Given the very limited available treatment options, further studies assessing its effectiveness and safety are necessary.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Ampicillin; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Retrospective Studies; Shock, Septic; Sulbactam; Trimethoprim, Sulfamethoxazole Drug Combination

Acinetobacter baumannii cause opportunistic nosocomial infections and is often multidrug resistant. It has ability to form biofilm. The possession of drug resistance mechanism and ability of biofilm formation seems to be the different way to enhancement of viability in stressful environment. In this study, we evaluate relation between these two factors. The biofilm formation was investigated in M63 medium with casein in microtiter plates, and the drug susceptibility was performed by disk diffusion methods. We found that 80-98% strains formed a biofilm. Strains showing sensitivity to amikacin and tobramycin from ICU produced more biofilm than strains showing resistance to these antibiotics. Ceftazidime-sensitive strains formed a smaller biofilm than resistant. The logistic regression shows association between drug resistance and strains originating from ICU. In case of ceftazidime, strong biofilm formation and descending from ICU reduced the likelihood of drug sensitivity. For other drugs such as aminoglycosides, fluoroquinolones, trimethoprim/sulfamethoxazole, and tetracycline, we found opposite relation (but it was not statistically significance). However, generally it seems that strong biofilm producers from ICUs are often more susceptible to antibiotics. This situation can be explained by the fact that bacteria protected in biofilm do not need mechanisms responsible for resistance of planktonic cells.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aminoglycosides; Anti-Bacterial Agents; Biofilms; Cephalosporins; Cross Infection; Culture Media; Drug Resistance, Multiple, Bacterial; Female; Fluoroquinolones; Humans; Intensive Care Units; Male; Microbial Sensitivity Tests; Middle Aged; Plankton; Trimethoprim, Sulfamethoxazole Drug Combination

The prevalence and antibiotic resistance of Acinetobacter spp. from fifty samples of meat (chicken, turkey, beef and pork) were evaluated. Acinetobacter spp. was recovered from all samples and the clonal relatedness of 223 isolates identified to belong to the genus Acinetobacter was established by PFGE. A high genetic diversity was observed and 166 isolates from different samples, 141 representing different PFGE profiles, were further identified to the species level by rpoB gene sequencing. Thirteen distinct Acinetobacter species were identified among 156 isolates. The remaining ten isolates may represent three putatively novel species since rpoB sequence homologies with type strains of all available described Acinetobacter species, were <95%. The most common species was Acinetobacter guillouiae with a prevalence of 34.9%. However 18.7% of the strains belong to the Acinetobacter baumannii group (n=31) which include the species Acinetobacter baumannii (n=7), Acinetobacter pittii (n=12), Acinetobacter seifertii (n=8) and Acinetobacter nosocomialis (n=4) that are the species most frequently associated with nosocomial infections worldwide. In general, strains were resistant to some of the antimicrobials most frequently used to treat Acinetobacter infections such as piperacillin-tazobactam (64.9% of strains resistant), ceftazidime (43.5%), ciprofloxacin (42.9%), as well as to colistin (41.7%) and polymyxin B (35.1%), the last-resort drugs to treat infections caused by multidrug-resistant Acinetobacter. The percentage of resistant strains to trimethoprim-sulfamethoxazole, tetracycline, aminoglycosides (amikacin and tobramycin) and ampicillin-sulbactam was >10% (23.2%, 23.2%, 14.3%, 12.5%, 12.5%, respectively). However, resistances to meropenem, imipenem and minocycline were only sporadically observed (8.3%, 1.2% and 1.2%, respectively). Overall, 51.2% of the strains were considered as multidrug-resistant (MDR) and 9.6% as extensively drug-resistant (XDR). The prevalence of MDR strains within the A. baumannii group (38.7%) was lower than the prevalence within the others species identified (54.1%). Therefore, food of animal origin may be a vehicle of spread Acinetobacter strains resistant to several antibiotics in the community and in the hospital setting environment. This may led to nosocomial and community-acquired infections in susceptible individuals.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Ampicillin; Animals; Anti-Bacterial Agents; Cattle; Ceftazidime; Chickens; Ciprofloxacin; Cross Infection; DNA-Directed RNA Polymerases; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prevalence; Red Meat; Sulbactam; Swine; Trimethoprim, Sulfamethoxazole Drug Combination

Acinetobacter baumannii (AB) has evolved a variety of resistance mechanisms and exhibits unpredictable susceptibility patterns, making it difficult to select empiric therapy.. To examine US secular trends in the resistance of AB in respiratory infections and blood stream infections (BSI) to antimicrobial agents whose effectiveness is supported in the literature. Survey.. We analyzed 3 time periods (2003-2005, 2006-2008, 2009-2012) in Eurofins' The Surveillance Network for resistance of AB to the following antimicrobials: carbapenems (imipenem, meropenem, doripenem), aminoglycosides (tobramycin, amikacin), tetracyclines (minocycline, doxycycline), polymyxins (colistin, polymyxin B), ampicillin-sulbactam, and trimethoprim-sulfamethoxazole. Resistance to ≥3 drug classes defined multidrug resistance (MDR).. We identified 39,320 AB specimens (81.1% respiratory, 18.9% BSI). The highest prevalence of resistance was to doripenem (90.3%) followed by trimethoprim-sulfamethoxazole (55.3%), and the lowest to colistin (5.3%). Resistance to carbapenems (21.0% in 2003-2005 and 47.9% in 2009-2012) and colistin (2.8% in 2006-2008 to 6.9% in 2009-2012) more than doubled. Prevalence of MDR AB rose from 21.4% in 2003 to 2005 to 33.7% in 2006 to 2008, and remained stable at 35.2% in 2009 to 2012. In contrast, resistance to minocycline diminished from 56.5% (2003-2005) to 30.5% (2009-2012). MDR organisms were most frequent in nursing homes (46.5%), followed by general ward (29.2%), intensive care unit (28.7%), and outpatient setting (26.2%).. Resistance rates among AB to such last-resort antimicrobials as carbapenems and colistin are on the rise, whereas that to minocycline has declined. Nursing homes are a reservoir of resistant AB. These trends should inform not only empiric treatment of serious infections, but also approaches to infection control.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Ampicillin; Anti-Bacterial Agents; Bacteremia; Carbapenems; Cross Infection; Drug Resistance, Bacterial; Humans; Intensive Care Units; Microbial Sensitivity Tests; Respiratory Tract Infections; Sulbactam; Surveys and Questionnaires; Trimethoprim, Sulfamethoxazole Drug Combination; United States

Acinetobacter calcoaceticus-A. baumannii complex (ACB complex) is a nosocomial pathogen. Due to its high ability to develop antibiotic resistance, it has become a problematic challenge in the modern healthcare system. The molecular and genetic mechanisms of gaining multidrug resistance in ACB complex are well known. This study focuses on providing an overview of the antibiotic resistance profiles, genetic similarities and resistotypes, and general characteristics of carbapenem-resistant ACB complex (CRACB) in Bosnia and Herzegovina (BiH). In light of the data collected in this study, together with the already known information concerning antibiotic resistance of ACB complex, we intend to further elucidate the antibiotic therapy for CRACB strain resistotypes in BiH.

Topics: Acinetobacter baumannii; Acinetobacter calcoaceticus; Acinetobacter Infections; Aminoglycosides; Anti-Bacterial Agents; Bacterial Typing Techniques; beta-Lactam Resistance; Bosnia and Herzegovina; Carbapenems; Clone Cells; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Phylogeny; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole alone and combined with colistin was tested in vitro against six carbapenem-resistant Acinetobacter baumannii (CRAB) clinical strains. After 24 h, at achievable serum concentrations, trimethoprim-sulfamethoxazole effectively killed all strains, while colistin killed only one strain. Trimethoprim-sulfamethoxazole plus colistin rapidly killed all strains after 6 h and for up to 24 h. Trimethoprim-sulfamethoxazole, one of the few remaining antimicrobials that still has a degree of activity, particularly combined with colistin, might represent an effective therapy for severe CRAB infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Microbial Sensitivity Tests; Trimethoprim, Sulfamethoxazole Drug Combination

Stenotrophomonas maltophilia (SM) is an important nosocomial pathogen that exhibits intrinsic resistance to various antimicrobial agents. However, the risk factors for SM bacteraemia have not been sufficiently evaluated. From January 2005 to September 2012, we retrospectively compared the clinical backgrounds and outcomes of SM bacteraemic patients (SM group) with those of bacteraemic patients due to Pseudomonas aeruginosa (PA group) or Acinetobacter species (AC group). DNA genotyping of the SM isolates using the Diversilab system was performed to investigate the genetic relationships among the isolates. The SM, PA, and AC groups included 54, 167, and 69 patients, respectively. Nine of 17 patients in the SM group receiving trimethoprim-sulfamethoxazole prophylaxis developed SM bacteraemia. Independent risk factors for SM bacteraemia were the use of carbapenems and antipseudomonal cephalosporins and SM isolation within 30 days prior to the onset of bacteraemia. Earlier SM isolation was observed in 32 of 48 patients (66.7%) with SM bacteraemia who underwent clinical microbiological examinations. Of these 32 patients, 15 patients (46.9%) had the same focus of bacteraemia as was found in the previous isolation site. The 30-day all-cause mortality rate among the SM group (33.3%) was higher than that of the PA group (21.5%, p = 0.080) and the AC group (17.3%, p = 0.041). The independent factor that was associated with 30-day mortality was the SOFA score. DNA genotyping of SM isolates and epidemiological data suggested that no outbreak had occurred. SM bacteraemia was associated with high mortality and should be considered in patients with recent use of broad-spectrum antibiotics or in patients with recent isolation of the organism.

Topics: Acinetobacter; Acinetobacter Infections; Adult; Aged; Bacteremia; Female; Gram-Negative Bacterial Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mortality; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Risk Factors; Stenotrophomonas maltophilia; Trimethoprim, Sulfamethoxazole Drug Combination

We report a case of pulmonary and bloodstream infection due to multiresistant Acinetobacter baumannii six days after a severe trauma. Clinical condition transiently improved following antimicrobial treatment with ticarcillin-clavulanate and rifampicin. However, a septic shock developed on the fourth day due to the emergence of a strain only sensible to cotrimoxazole, colistin and tigecycline. Cure was achieved after a two week treatment with piperacillin-tazobactam, cotrimoxazole and tigecycline. This case shows that combined antimicrobial therapy including tigecycline can be relevant in some severe pulmonary infections due to multiresistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Anti-Bacterial Agents; Anti-Infective Agents; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Minocycline; Penicillanic Acid; Piperacillin; Shock, Septic; Tazobactam; Tigecycline; Trimethoprim, Sulfamethoxazole Drug Combination

We tested whether antibiotic susceptibilities of drug-resistant Acinetobacter baumannii isolates could be used to predict the clinically important genotypes bla(TEM-1), AmpC-type bla, and integrase 1 gene (IntI1).. We analyzed 401 A. baumannii isolates obtained at Changhua Christian Hospital between April 2001 and March 2002. The isolates were all from blood cultures, and identification of A. baumannii was confirmed by API-20NE. Antibiotic susceptibility testing (phenotype) was performed by disk diffusion method. Polymerase chain reaction was used to detect the genes bla(TEM-1), AmpC-type bla and IntI1.. Of 32 A. baumannii isolates, 10 possessed bla(TEM-1), 21 AmpC-type bla, and 26 IntI1. Resistance to ceftazidime (CAZ) predicted bla(TEM-1) genotype with 63.6% sensitivity, 100% specificity, 55.6% positive predictive value (PPV) and 0% negative predictive value (NPV). Trimethoprim-sulfamethoxazole (SXT) and gentamicin (GM) resistance predicted IntI1 genotype with 83.3% sensitivity, 71.4% specificity, 95.2% PPV and 45.4% NPV. No resistance phenotype could predict the AmpC-type bla genotype.. CAZ resistance predicted the bla(TEM-1) genotype with 100% specificity, and SXT and GM resistance predicted the IntI1 genotype with 92.5% PPV. Therefore, antibiotic susceptibilities to CAZ, SXT, and GM can be utilized clinically to detect critical genotypes in A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Proteins; beta-Lactamases; Biomarkers; Ceftazidime; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Genes, Bacterial; Gentamicins; Humans; Integrases; Microbial Sensitivity Tests; Molecular Sequence Data; Prospective Studies; Species Specificity; Taiwan; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acinetobacter; Acinetobacter Infections; Adult; AIDS-Related Opportunistic Infections; Community-Acquired Infections; Humans; Male; Pneumonia, Bacterial; Trimethoprim, Sulfamethoxazole Drug Combination

A 65 year old man was admitted with segmental consolidation of the left upper lobe after having stayed in a hotel for 2 days. He deteriorated rapidly on conventional antibiotic therapy and required ventilatory support. Acinetobacter calcoaceticus var. anitratus was grown from the sputum and blood cultures, which was treated with a combination of anti-pseudomonal agent, aminoglycoside and cotrimoxazole. He made a slow but remarkable recovery from the pneumonia. Acinetobacter is a rare potentially fatal cause of community-acquired pneumonia.

Topics: Acinetobacter Infections; Aged; Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Community-Acquired Infections; Drug Therapy, Combination; Humans; Male; Pneumonia; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acinetobacter Infections; Blood; Drug Combinations; Humans; Male; Middle Aged; Pleural Effusion; Pneumonia; Sulfamethoxazole; Tobramycin; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acinetobacter Infections; Cross Infection; Drug Combinations; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Meningitis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination