TABLE 10.
Randomized clinical trials (RCTs) for hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP)
| Reference | Regimen | Population | Disease severity | Setting | Response | Comments |
|---|---|---|---|---|---|---|
| 261 | Ceftazidime (CTZ) 2 g q8h IV versus ticarcillin (TIC) 3 g q4h IV + tobramycin (T) IV with peak levels of 5–7 mg/mL and troughs of 1.5–2.0 mg/mL | >18 years old, neurosurgical patients MV NA | Moderate | ICU | Clinical cure | Open label RCT |
| (CTZ) n=17 | (CTZ) 88% | |||||
| (TIC + T) n=18 | (TIC + T) 83% | |||||
| 374 | Cefotaxime (CFT) 2 g q6h IV with aztreonam (AZ) 1 g q8h IV or amikacin (AM) 500 mg q12h IV | Adults (>20 years old), MV NA | Moderate-severe | ICU | Clinical cure | Open label RCT |
| (CFT+AZ) n=13, | (CFT+AZ) 77%, | |||||
| (CFT+AM) n=16 | (CFT+AM) 75% | |||||
| 375 | Ciprofloxacin (CIP) 300 mg q12h IV versus CTZ 2 g q8h IV | >18 years old | Moderate | Ward-ICU | Clinical response | Double-blind RCT |
| MV 59% (CIP) | (CIP) n=17 | (CIP) 88.2% | ||||
| MV 73% (CTZ) | (CTZ) n=15 | (CTZ) 86.2% | ||||
| 262 | Imipenem (I) 500 mg q6h IV or I 500 mg q6h IV + netilmicin (N) 50 mg q12h IV | >16 years old | Moderate | Ward-ICU | Success | Open label RCT |
| MV 52.7% (I) | (I) n=91 | (I) 82.4% | ||||
| MV 56.9% (I+N) | (I+N) n=86 | (I+N) 83.7% | ||||
| 263 | CTZ 2 g q12h IV versus ceftriaxone (CRX) 2 g IV qd + T 3–5 mg/kg/d IV | Adults | Moderate-severe | Ward-ICU | Clinical response | Open label RCT |
| ICU 43%, | (CTZ) n=159 | (CTZ) 73% | ||||
| MV 65% | (CRX+T) n=138 | (CRX+T) 65%, P=0.09 | ||||
| 376 | CIP 300 mg q12h IV 750 mg q12h po after 72 h versus CTZ 2 g q8h IV | >18 years old | Moderate-severe | Ward-ICU | Clinical response at 96 h | Open label RCT |
| MV 52.8% (CIP), | (CIP) n=56 | (CIP) 87.1% | ||||
| MV 50.7% (CTZ) | (CTZ) n=68 | (CTZ) 87.3% | ||||
| 91 | Cefepime (CPM) 2 g q8h IV versus I 500 mg q6h IV | >16 years old | Severe | ICU | Clinical response | Open label RCT |
| MV 66% (CPM), | (CPM) n=108 | (CPM) 70% | ||||
| MV 66% (I) | (I) n=101 | (I) 74% | ||||
| 270 | Quinupristin/dalfopristin (Q/D) 7.5 mg/kg q8h IV +/− aztreonam 2 g q8h IV versus vancomycin (V) 1 g q12h IV± aztreonam 2 g q8h IV | >18 years old, | Moderate-severe | Ward-ICU | Clinical response7–13 d post therapy in bacteriologically evaluable patients, | Open label RCT |
| MV 74% (Q/D) | (Q/D) n=87 | (Q/D) 56.3% | ||||
| MV 68.9% (V) | (V) n=84 | (V) 58.3% | ||||
| 268 | Linezolid (L) 600 mg q12h IV or V 1 g q12h IV with aztreonam 1–2 g q8h IV | >18 years old, | Moderate-severe | Ward-ICU | Clinical response 15–21 d post-therapy | Double-blind RCT |
| MV 50.5% (L) | (L) n=169 | (L) 67.9% | ||||
| MV 50.7% (V) | (V) n=176 | (V) 64.9% | ||||
| 269 | L 600 mg q12h IV or V 1 g q12h IV plus aztreonam 1–2 g q8h IV | >18 years old | Moderate-severe | Ward-ICU | Clinical response in evaluable patients with12–28 d follow-up | Double-blind RCT |
| MV 58.2% (L) | (L) n=107 | (L) 66.4% | ||||
| MV 56.4 (V) | (V) n=91 | (V) 68.1 % | ||||
| 206 | L 600 mg q12h IV or V 1 g q12h IV +/− aztreonam 1–2 g q8h IV | >18 years old | Moderate-severe | Ward-ICU | Clinical cure at end of therapy | Double-blind RCTs with (L) versus (V) combined |
| MV 70.2% (L) | S aureus | S aureus | ||||
| MV 66.7% (V) | (L) n=136 | (L) 51.5% | ||||
| (V) n=136 | (V) 43.4% | |||||
| MRSA | MRSA | |||||
| (L) n=61 | (L) 59.0% | |||||
| (V) n=62 | (V) 35.5%, P<0.001 | |||||
| 88 | Levofloxacin (LEV) 750 mg q24h IV then po versus I 500–1000 mg q6–8h IV then CIP 750 mg BID po | >18 years old | Moderate-severe | Ward-ICU | Clinical response in microbiological efficacy patients at 7–15 d post-therapy | Open label RCT |
| MV 71.4% (LEV) | (LEV) n=93 | (LEV) 58.1% | ||||
| MV 70.6% (I) | (I) n=94 | (I) 60.1% | ||||
| 377 | CPM 2 g q12h IV versus CFT 2 g q8h IV | >18 years old | Moderate-severe | Ward-ICU | Clinical response at follow-up | Open label RCT; 2:1 randomization |
| MV 54% (CPM) | (CPM) n=18 | (CPM) 83% | ||||
| MV 62% (CFT) | (CFT) n=5 | (CFT) 40% | ||||
| 150 | Meropenem (M) 1 g q8h IV versus I 1 g q8h IV | >16 years old, % MV NA | Moderate-severe | Ward-ICU | Clinical response at end of therapy | Open label RCT |
| (M) n=36 | (M) 75% | |||||
| (I) n=44 | (I) 75% | |||||
| 82 | M 1 g q8h IV versus CTZ 2 g q8h IV ± T 1 mg/kg q8h IV | > 17 years old | Moderate-severe | Ward-ICU | Clinical response at end of therapy | Open label RCT |
| MV 73% (M) | (M) n=63 | (M) 89% | ||||
| MV 67% (CTZ+T) | (CTZ+T) n=58 | (CTZ+T) 72%, P=0.04 | ||||
| 378 | M 1 g q8h IV versus I 1 g q8h IV | >16 years old | Moderate-severe | Ward-ICU | Clinical response at end of therapy | Open label RCT |
| MV 73% (M) | (M) 91% | |||||
| MV 72% (I) | (I) 78% |
Mechanical ventilation (MV) >75% = VAP; MV 50% to 75% = HAP/VAP; MV <50% = HAP. BID Twice daily; d Day; ICU Intensive care unit; IV Intravenous; NA Not available; po By mouth; q Every; MRSA Methicillin-resistant Staphylococcus aureus (S aureus)