Moxalactam plus piperacillin versus moxalactam plus amikacin in febrile granulocytopenic patients

In a prospective randomized trial, febrile granulocytopenic patients received either moxalactam plus piperacillin or moxalactam plus amikacin as initial empiric antimicrobial therapy. Most patients were also given prophylactic vitamin K. The overall response rates for the two regimens were similar (105 of 136, or 77 percent, for moxalactam plus piperacillin versus 107 of 136, or 79 percent, for moxalactam plus amikacin). For Pseudomonas aeruginosa infections, the response rate was better in patients receiving moxalactam plus amikacin (seven of nine versus one of five, p = 0.06); two patients treated with moxalactam plus piperacillin experienced relapse of P. aeruginosa bacteremia in association with the emergence of beta-lactam-resistant P. aeruginosa isolates. On the other hand, bacteremic enterococcal superinfections occurred in seven patients receiving moxalactam plus amikacin but in none given moxalactam plus piperacillin (p = 0.02). Serious side-effects were minimal with both regimens, and nephrotoxicity was less common in patients receiving moxalactam plus piperacillin (two of 136 versus six of 136, p = 0.28). There was no antibiotic-related hemorrhage. These results suggest that the overall efficacy and toxicity of moxalactam plus piperacillin and moxalactam plus amikacin are similar. Moxalactam/piperacillin therapy may be limited in certain patients by the emergence of beta-lactam-resistant P. aeruginosa, whereas enterococcal superinfections may complicate moxalactam/amikacin therapy.     

Beta-lactam antibiotic therapy in febrile granulocytopenic patients. A randomized trial comparing cefoperazone plus piperacillin, ceftazidime plus piperacillin, and imipenem alone

OBJECTIVE: To compare the efficacy, toxicity, and cost-effectiveness of double beta-lactam therapy with monotherapy. DESIGN: A randomized, controlled trial. PATIENTS: Febrile, granulocytopenic patients (429). INTERVENTIONS: Patients were randomly assigned to receive iv cefoperazone (3 g every 12 hours) plus piperacillin (75 mg/kg body weight every 6 hours), ceftazidime (2 g every 8 hours) plus piperacillin (75 mg/kg every 6 hours), or imipenem alone (1.0 g or 0.5 g every 6 hours). Patients also received prophylactic vitamin K. MEASUREMENTS: Clinical improvement, eradication of the infecting organism, and toxicity in 403 evaluable patients with one or more infections. MAIN RESULTS: Cefoperazone and ceftazidime, when given in combination with piperacillin, were equally effective (response rates of 75% (104 of 138 patients) and 74% (101 of 137 patients), respectively). Monotherapy with imipenem had a response rate of 82% (111 of 136 patients) and was as effective as double beta-lactam therapy. Overall antibiotic-related toxicity was minimal, although seizures were associated with high doses of imipenem. Seizures occurred in 3 of 29 patients (10.3%) who were receiving 4 g/d of imipenem, in 3 of 136 patients (2.2%) who were receiving cefoperazone plus piperacillin, in 0 of the 132 patients who were receiving ceftazidime plus piperacillin, and in 1 of 106 patients (0.9%) who were receiving 2 g/d of imipenem (P less than 0.005). The 2-g daily dose of imipenem was as effective as the 4-g daily dose. Diarrhea was more frequent in patients receiving cefoperazone, whereas nausea occurred more often with imipenem. No antibiotic-related hemorrhage or nephrotoxicity was observed. Superinfections caused by beta-lactam-resistant, gram-negative bacilli were uncommon but occurred more frequently with double beta-lactam therapy than with imipenem monotherapy (11 of 268 patients compared with 1 of 135 patients; P = 0.06). Xanthomonas maltophilia superinfections occurred only in patients receiving imipenem (3 of 135 patients compared with 0 of 268 patients; P = 0.03). Imipenem monotherapy was the least expensive therapy. CONCLUSIONS: Cefoperazone and ceftazidime were equally effective when used in combination antibiotic therapy with piperacillin. Twice-daily cefoperazone is less expensive than ceftazidime given three times daily. Monotherapy with imipenem, at a daily dose of 2 g, is as efficacious as double beta-lactam therapy and costs less than combination therapy.     

Comparison of piperacillin alone versus piperacillin plus tobramycin for treatment of respiratory infections in children with cystic fibrosis

Seventeen patients with cystic fibrosis (CF) and pulmonary exacerbations were randomly assigned to two treatment groups: piperacillin 600 mg/kg/day (P), and piperacillin 600 mg/kg/day plus tobramycin (PT), in order to determine the safety and pharmacokinetics of high-dose piperacillin and whether piperacillin alone was effective for the treatment of Pseudomonas infections. The mean half-life of piperacillin was 0.54 hours, with a peak concentration of 232 micrograms/ml. No differences between P and PT groups were noted in clinical assessment, as judged by Shwachman scores, pulmonary function testing, or weight gain. However, during the course of treatment, quantitative sputum cultures decreased by greater than 10(2) colony-forming units in only 5 out of 19 Pseudomonas isolates from the P group, compared with 12 of 19 isolates from the PT group (P less than 0.03, Chi-square). Although emergence of resistance was not seen, one isolate had an increase in minimum inhibitory concentration from 8 to 128 micrograms/ml. There were no serious adverse reactions to piperacillin; only one patient developed fever possibly related to piperacillin. Therapy with high-dose piperacillin was safe in children with CF. Treatment with piperacillin alone was less effective than combination therapy with gentamicin for reduction in titer of Pseudomonas in sputum. However, the role of antimicrobial agents in the treatment of CF remains undefined. A double-blind placebo-controlled trial is indicated.     

Conjugative resistance to tazobactam plus piperacillin among extended-spectrum beta-lactamase-producing nosocomial Klebsiella pneumoniae

We studied the genetic origins of piperacillin-tazobactam resistance among nosocomial Klebsiella pneumoniae strains. A total of 30 nosocomial isolates resistant to piperacillin-tazobactam were obtained from various regions of Turkey. Isoelectric focusing demonstrated at least 2 enzymes common to all strains: I at a pI of 8.0 and the other at 5.4. Piperacillin-tazobactam resistance was successfully transferred from all of the strains to Escherichia coli. Of the piperacillin-tazobactam-resistant transconjugates, 23 were also resistant to ceftazidime. However, 7 transconjugates were susceptible to ceftazidime but resistant to piperacillin-tazobactam, producing a single enzyme focusing at pI 5.4. Piperacillin resistance caused by this enzyme was reversed by clavulanate and by increased amounts of tazobactam, which indicates that this enzyme confers resistance due to its high amount. Sequence analysis revealed this enzyme to be TEM-1. This study demonstrates that transferable hyper-produced TEM-1 causes piperacillin-tazobactam resistance in Klebsiella strains in Turkish hospitals.     

Piperacillin plus amikacin vs. piperacillin plus amikacin plus teicoplanin for empirical treatment of febrile episodes in neutropenic patients receiving quinolone prophylaxis.

A prospective, randomized trial was initiated to evaluate the efficacy of two antibiotic regimens, differing in the agent included with activity against gram-positive bacteria, for the empirical treatment of febrile episodes in neutropenic patients with hematologic malignancies (group 1, piperacillin plus amikacin; group 2, piperacillin plus amikacin plus teicoplanin). After 72 hours of therapy, patients in group 1 who were still febrile were administered teicoplanin and those in group 2 were administered amphotericin B. A total of 158 evaluable episodes were observed within 8 months. The success rate was 50.6% in group 1 and 60% in group 2. The response rate among patients who did not respond to the original regimen increased to 86.7% with the addition of teicoplanin (group 1) and to 90% with the addition of amphotericin B (group 2). There were 86 unexplained febrile episodes and 56 documented episodes of bacteremia (34 caused by gram-positive organisms). Our results indicate that teicoplanin is safe, well tolerated, and effective for the treatment of documented episodes of gram-positive bacteremia and as an empirical agent. The inclusion of teicoplanin in the initial empirical regimen appears unnecessary if a combination of antibiotics active against gram-positive organisms is used, unless infections are due to oxacillin-resistant staphylococci.     

Amikacin plus piperacillin versus ceftazidime as initial therapy in granulocytopenic patients with presumed bacteremia

69 febrile granulocytopenic episodes without an initial focus of infection were assessed for empiric treatment either with high-dose amikacin plus piperacillin or ceftazidime. 90% of patients in each group survived the granulocytopenic episode; 15 (44 +/- 17%) episodes treated with the combination and 23 (66 +/- 16%) given ceftazidime responded without any modification of initial therapy and half defervesced within 72 h. Persistent fever was the most frequent reason for altering treatment which was done empirically in 90% of cases, but two-thirds of patients required further treatment modification. An infectious focus mainly involving the lung developed during granulocytopenia in 21 patients (30%), of which 17 occurred during antimicrobial therapy. Only 1 infection was shown to be due to bacteria, while 7 were due to fungi. Amikacin levels were similar to those expected following a normal dose (mean peak of 34.7 and mean trough of 12.6 mg/l). Therapy with the combination resulted in a higher serum creatinine (p less than 0.001) and a lower potassium level (p less than 0.001) in comparison with monotherapy. Potassium supplementation was required in 45 +/- 17% of patients given the combination compared with only 4 +/- 7% of those treated with ceftazidime. While both regimens appeared to be equally effective as initial therapy, the need for modification was high in both patient groups. Monotherapy being both simpler to administer and less toxic seems therefore to be the logical choice although the period of empiric therapy must be fully exploited in order to improve diagnosis and therefore antimicrobial management.     

A randomized study of teicoplanin plus ciprofloxacin versus gentamicin plus piperacillin for the empirical treatment of fever in neutropenic patients

S ummary We compared the combination of teicoplanin plus ciprofloxacin with gentamicin plus piperacillin for the empirical treatment of fever in 80 neutropenic patients. A favourable clinical response rate was achieved in 28/38 (74%) patients receiving teicoplanin plus ciprofloxacin and in 17/ 35 (49%) of those receiving gentamicin plus piperacillin (P = 0.05). Microbiologically documented infections accounted for 55% of febrile events. When these episodes were analysed separately, response to teicoplanin plus ciprofloxacin remained unchanged at 74% whereas only 35% patients responded to gentamicin and piperacilin (P=0.034). Gram-positive organisms accounted for 78% bacterial isolates with Staphylococcus epidermidis the most common pathogen. Ten out of 12 (83%) Staph. Epidermidis infections resolved when treated with teicoplanin and ciprofloxacin as compared with a response rate of only two out of eight (75%) with gentamicin and piperacillin (P = 0.032). The combination of teicoplanin and ciprofloxacin was associated with no severe drug-related adverse events: by contrast, two patients receiving gentamicin plus piperacilin were withdrawn owing to adverse drug reactions, one with acute renal failure and one following a severe allergic reaction to piperacillin. We conclude that teicoplanin with ciprofloxacin is more effective than gentamicin plus piperacillin for the empirical treatment of febrile neutropenic patients. The high incidence of Gram-positive infection in our unit probably justifies the use of a specific anti-Gram-positive agent in the first-line antibiotic regimen.     

A comparative efficacy and safety study of teicoplanin plus aztreonam versus gentamicin plus piperacillin in haematology oncology patients with clinically diagnosed septicaemia

S ummary Infections due to Gram-positive bacteria, especially coagulase-negative staphylococci. have been increasing in immunocompromised patients during the last 5 years because of an increased use of Hickman catheters and oral gut decontamination with quinolones. Teicoplanin. a new glycopeptide antibiotic. has a long plasma half-life which allows once-a-day bolus administration, making it a'user friendly'agent. A randomized comparative evaluation of teicoplanin plus aztreonam versus gentamicin plus piperacillin in leukaemic patients with a clinical diagnosis of septicaemia was undertaken. The objectives of this study were (1) to evaluate the efficacy and safety of teicoplanin and aztreonam in comparison to a 'standard antibiotic'regimen and (2) to assess the local and systemic tolerance of these drugs. Results of the study in more than 70 patients to date are presented, and the role of anti-Gram-positive antibiotics in the management of severe sepsis in immunocompromised patients is discussed.     

In vitro comparison of mezlocillin and piperacillin plus tobramycin or gentamicin versus 100 gram-negative nosocomial bloodstream isolates

We compared the in vitro activity of mezlocillin and piperacillin, alone and in combination with tobramycin or gentamicin, against clinical isolates of gram-negative bacilli from hospitalized patients with 100 distinct episodes of nosocomial bacteremia. The minimum inhibitory concentrations (MICs) necessary to inhibit 50% and 90% of isolates showed that piperacillin was most active against Pseudomonas aeruginosa. The MIC needed to inhibit 90% of isolates also showed that mezlocillin was more active against Enterobacter cloacae. Activities of the two acylaminopenicillins were comparable against the rest of the isolates. Combining the acylaminopenicillins with either gentamicin or tobramycin decreased the MICs fourfold or more for both combinations. Synergy occurred more frequently with mezlocillin-gentamicin (12%), followed by piperacillin-tobramycin (9%), mezlocillin-tobramycin (6%), and piperacillin-gentamicin (5%). Antagonism for Enterobacteriaceae isolates was observed most frequently with the combination of piperacillin plus tobramycin (20%), followed by mezlocillin plus tobramycin (17.6%), piperacillin plus gentamicin (12.9%), and mezlocillin plus gentamicin (8.2%). There are very few differences in the activities of mezlocillin and piperacillin combined with either gentamicin or tobramycin versus nosocomial gram-negative bloodstream isolates.     

Treatment of Pseudomonas lung infection in cystic fibrosis with piperacillin plus tobramycin versus ceftazidime monotherapy: preliminary communication

Twenty-one patients with cystic fibrosis and chronic Pseudomonas lung infection were treated at random with ceftazidime, 150 mg/kg/day, or with piperacillin, 300 mg/kg/day, and tobramycin, 10 and more mg/kg/day for 14 days. On admission and at discharge, body weight, erythrocyte sedimentation rate, white blood cell count, and differential were determined. Pulmonary function analysis and chest X-rays were also obtained on both occasions as was sputum bacteriology. After hospitalization, the patients were followed in the outpatient department for 14-26 months. Both treatments were associated with significant improvement in most of the parameters that were studied, but neither treatment was superior.     

A randomized study of imipenem compared to cefotaxime plus piperacillin as initial therapy of infections in granulocytopenic patients

Summary The objective of the presented, randomized study was to compare the efficacy of antimicrobial monotherapy with imipenem (3×0.5g/d) to a combination therapy with cefotaxime (3×2g/d) plus piperacillin (3×4g/d) for empirical treatment of infections in neutropenic patients. In 165 patients, 237 infectious episodes were evaluable. The overall response rate of patients treated with cefotaxime plus piperacillin was 67/115 (58%), of those treated with impienem 66/122 (54%). In patients not responding to the initial therapy regimen within 2 or 3 days, the antimicrobial therapy was modified. After therapy modification 85/100 patients were cured. Fever of unknown origin (FUO) showed the most favourable course compared to other infection types, with a response in 46/59 (78%) and in 35/50 (70%) cases, respectively. In comparison, pneumonias were successfully treated in only 3/21 (14%) and 7/37 (19%) cases. Even including patients with modified therapy, only 66% (21/32) of pneumonia episodes responded. The unfavourable results in pneumonias is mainly due to the high rate of 13 systemic mycoses in this group (22%). Overall, a similar response was observed in patients treated with cefotaxime plus piperacillin in comparison with imipenem. In primary bacteremias however, an advantage was observed in patients treated with imipenem (20/27; 74%) compared with cefotaxime plus piperacillin (11/23; 48%).

---

Randomisierte Studie mit Imipenem versus Cefotaxim/Piperacillin in der Initialtherapie von Infektionen granulozytopenischer Patienten

Zusammenfassung Ziel der vorliegenden prospektiven, randomisierten Studie war der Vergleich der Effektivität einer Monotherapie mit Imipenem (3×0,5g/Tag) gegenüber einer Kombinationstherapie mit Cefotaxim (3×2g/Tag) plus Piperacillin (3×4g/Tag) in der Initialtherapie von Infektionen granulozytopenischer Patienten. 237 Infektionsepisoden bei 165 Patienten waren evaluierbar. Insgesamt wurde unter Cefotaxim plus Piperacillin eine Heilung in 67/115 (58%), unter Imipenem in 66/122 Episoden (54%) erzielt. Bei Nichtansprechen innerhalb von drei Tagen unter der Initialtherapie wurde die antibiotische Behandlung modifiziert. Hierdurch wurde bei weiteren 85/100 Patienten eine Heilung erreicht. Unter den verschiedenen Infektionstypen war die Ansprechrate bei Fieber unklarer Genese (FUO) am höchsten mit einem Therapieerfolg in 46/59 Episoden unter Cefotaxim plus Piperacillin (78%) sowie in 35/50 Fällen unter Imipenem (70%). Besonders ungünstig verliefen dagegen die Pneumonien mit einem Ansprechen in 3/21 (14%) bzw. in 7/37 (19%) der Fälle. Auch unter Therapiemodifikation ergab sich hier eine Ansprechrate von insgesamt lediglich 66% (21/32). Die ungünstigsten Ergebnisse bei diesem Infektionstyp sind hauptsächlich durch den hohen Anteil von 13 systemischen Pilzinfektionen bei den Pneumonien (22%) bedingt. Insgesamt zeigten sich keine signifikanten Unterschiede in der Ansprechrate unter Cefotaxim plus Piperacillin im Vergleich zu Imipenem. Bei den primären Bakteriämien zeigte sich jedoch eine höhere Ausheilungsrate unter Imipenem mit 20/27 Episoden (74%) im Vergleich zu Cefotaxim plus Piperacillin mit 11/23 (48%) Episoden.

     

Ciprofloxacin plus piperacillin is an equally effective regimen for empiric therapy in febrile neutropenic patients compared with standard therapy

The purpose of this study was to test the comparative efficacy and toxicity of empiric gentamicin and ciprofloxacin, in combination with piperacillin, in febrile patients with treatment-induced neutropenia. Fifty patients were prospectively randomized to receive piperacillin plus gentamicin (PG), and 46 were randomized to receive piperacillin plus ciprofloxacin (PC). The groups were similar in age, sex, diagnosis, duration of neutropenia, and incidence of positive cultures. The two antibiotic regimens were associated with comparable rates of defervescence in the patients with Gram-positive bacteremia. In the patients with Gram-negative bacteremia and those with negative cultures, however, defervescence was more prompt in the PC group. In particular, 27% of the culture-negative patients on PC, compared to only 5% of those on PG, defervesced within 72 hr (P = 0.015). Because of the more prompt defervescence in the PC group, amphotericin B was used less frequently; 78% of the patients on PG compared with only 56% of those on PC were started on amphotericin B (P J Biomed Mater Res, 41, = 0.025). PC is an effective alternative to the more traditional PG for treatment of febrile neutropenic hosts who have not been given prophylactic quinolones. More important, PC appears to hasten defervescence compared with PG, especially in culture-negative patients and those with Gram-negative bacteremia, and may decrease the necessity of additional antimicrobial agents such as amphotericin B. 1998. Am. J. Hematol. 58: 293–297, 1998. © 1998 Wiley-Liss, Inc.     

Empiric antimicrobial therapy in febrile granulocytopenic patients. Randomized prospective comparison of amikacin plus piperacillin with or without parenteral trimethoprim/sulphamethoxazole

Summary In a prospective randomized trial parenteral trimethoprim/sulphamethoxazole was added to amikacin plus piperacillin in order to compare triple-drug antibiotic combination with a standard regimen as empiric therapy of fever in patients with granulocytopenia. One hundred and sixty-one episodes were evaluated; 74 episodes with amikacin plus piperacillin and 87 episodes with amikacin plus piperacillin plus trimethoprim/sulphamethoxazole. The overall response to therapy (63% vs. 84%) as well as the response of microbiologically documented infections (60% vs. 82%) was significantly better in patients treated with the triple-drug combination (p < 0.05). However, no statistically significant differences in response to antibiotics at different infection sites or with regard to any single pathogen was found between the two groups. Trimethoprim/sulphamethoxazole seemed to be responsible for additional toxicity (nausea and vomiting) when added to amikacin plus piperacillin, but these side-effects were clearly related to the rate of infusion of trimethoprim/sulphamethoxazole. The findings of this study support the use of a three-drug versus a two-drug combination as empiric antibiotic regimen in febrile granulocytopenic patients.

---

Empirische antimikrobielle Therapie bei granulozytopenischen Patienten mit Fieber. Randomisierte, prospektive Vergleichsstudie zur Therapie mit Amikacin plus Piperacillin mit oder ohne Zusatz von parenteralem Trimethoprim/Sulfamethoxazol

Zusammenfassung In einer prospektiven, randomisierten Studie wurde die Kombination Amikacin plus Piperacillin plus Trimethoprim/Sulfamethoxazol mit der Standard-Zweierkombination Amikacin-Piperacillin in der empirischen Behandlung von Fieberschüben bei granulozytopenischen Patienten verglichen. 161 Fieberepisoden wurden ausgewertet, davon waren 74 mit Amikacin plus Piperacillin und 87 mit Amikacin plus Piperacillin plus Trimethoprim/Sulfamethoxazol behandelt worden. Bei Patienten, die die Antibiotika-Dreierkombination erhalten hatten, war der Gesamt-Therapieerfolg wie auch das Ansprechen mikrobiologisch nachgewiesener Infektionen mit 84% bzw. 82% signifikant besser als bei Patienten, die nur Amikacin-Piperacillin erhalten hatten, mit Ansprechraten von 63% bzw. 60% (p < 0,05). Bei Auswertung der Ansprechraten nach Infektionslokalisation oder Erregern fanden sich hingegen keine signifikanten Unterschiede zwischen den beiden Gruppen. Die Zugabe von Trimethoprim/Sulfamethoxazol zu Amikacin-Piperacillin verstärkte offensichtlich die Toxizität der Antibiotikatherapie mit vermehrtem Auftreten von Übelkeit und Erbrechen, doch standen diese Nebenwirkungen eindeutig in Beziehung zur Infusionsgeschwindigkeit von Trimethoprim/Sulfamethoxazol. Die Ergebnisse dieser Studie sprechen für die Verwendung einer Kombination von drei Antibiotika anstelle einer Zweierkombination in der empirischen Therapie von Fieberschüben bei granulozytopenischen Patienten.

     

Hypercoagulopathy with piperacillin administration in osteomyelitis

A 51-year-old man with osteomyelitis developed acute renal failure and superior mesenteric venous (SMV) thrombosis after piperacillin (PIPC) treatment. Coagulation profile disclosed disseminated intravascular coagulation (DIC). The serum levels of IgE and eosinophil cationic protein showed significant increases, while a lymphocyte stimulation test with PIPC also demonstrated an extremely high index. These observations suggest that hypersensitivity to PIPC might play a role in the pathogenesis of acute renal failure and SMV thrombosis due to hypercoagulopathy. Withdrawal of PIPC and anticoagulation therapy resulted in clinical improvement and normalization of the affected laboratory data. This is the first report to describe PIPC-induced hypercoagulopathy.     

Cefepime challenge after piperacillin/tazobactam-induced thrombocytopenia

Journal of Thrombosis and Thrombolysis - Drug-induced thrombocytopenia (DITP) has been described as a sudden and severe hematologic complication of piperacillin/tazobactam. The proposed mechanism...     

Clinical effects of piperacillin and tazobactam/piperacillin on Haemophilus influenzae lower respiratory tract infection in pediatric patients

OBJECTIVE: The prevalence of beta-lactamase-nonproducing ampicillin-resistant (BLNAR) Haemophilus influenzae (H. influenzae) has been increasing in recent years. Piperacillin (PIPC) is one of a few beta-lactams possessing good activity against BLNAR H. influenzae. We studied clinical efficacy of piperacillin and its beta-lactamase inhibitor, tazobactam/piperacillin (TAZ/PIPC) in children with lower respiratory tract infection caused by H. influenzae including resistance strains. METHODS: Subjects were 20 children with lower respiratory tract infection caused by H. influenzae treated with PIPC 100mg/kg/day (7 cases) or TAZ/PIPC 125mg/kg/day (13 cases). We selected cases from which resistant H. influenzae strains might be detected. Patients received prior antimicrobial therapy within two weeks before admission, or with underlying diseases. We examined patient profiles, clinical efficacy, susceptibilities for 6 beta-lactam antibiotics [PIPC, TAZ/PIPC, ampicillin (ABPC), cefotaxime (CTX), ceftriaxone (CTRX), and meropenem (MEPM)] and analyzed 6 genotype patterns of beta-lactam resistant genes by PCR. RESULTS: Efficacy was 7/7 in patients in PIPC group and 12/13 in patients in TAZ/PIPC group. Diminished efficacy was seen in only one case complicated with severe RSV infection. The susceptibility of all strains but one beta-lactamase producing, ABPC resistant (BLP) strain to PIPC and of all to TAZ/ PIPC was below 0.25 microg/mL. The genotype of the 15 strains isolated from the sputum on administration was as follows; beta-lactamase nonproducing, ABPC-susceptible (gBLNAS) strains were 4, gBLP strain was 1, beta-lactamase nonproducing, and ABPC-resistant (gLow-BLNAR) strains were 2, beta-lactamase nonproducing, ABPC resistant (gBLNAR) strains were 8. CONCLUSION: PIPC and TAZ/PIPC were useful against lower respiratory tract infection caused by H. influenzae including BLNAR in children.     

Thrombocytosis under ciprofloxacin and tazobactam/piperacillin

Whether the simultaneous administration of ciprofloxacin or tazobactam/piperacillin increases the risk of thrombocytosis is unknown. Broncho-pulmonary infection in a 50-year-old male with acute, hypertensive, intracerebral bleeding, necessitated therapy with cefpirome (2 g/day, 6 days), ciprofloxacin (800 mg/d, 11 days) and tazobactam/piperacillin (9 g/day, 11 days). Starting with the 8th hospital day, the thrombocyte count steadily increased from 410000/µl to a maximum of 1132000/µl on hospital day 16. Afterwards the thrombocyte count continuously decreased to normal values. Primary thrombocytosis and secondary causes were excluded. Since the thrombocyte count started to increase immediately after initiation and dropped immediately after discontinuation of ciprofloxacin and tazobactam/piperacillin and all other drugs were discontinued already before or were started after the nadir of the thrombocyte count, these two antibiotics were regarded causative. It is concluded that simultaneous administration of ciprofloxacin and tazobactam/piperacillin may cause marked thrombocytosis. Discontinuation of these two antibiotics results in an immediate decline of the thrombocyte count to normal values within three weeks.